Scientific Program

Conference Series Ltd invites all the participants across the globe to attend Annual Conference and Expo on Biomaterials London, UK.

Day 2 :

  • Track-5: Biomaterials Applications
    Track-2: Polymer Biomaterials
    Track-17: 3D Printing of Biomaterials
Speaker

Chair

Andrew Lewis

Biocompatibles UK Ltd, UK

Speaker

Co-Chair

George Youssef

San Diego State University, USA

Speaker
Biography:

Andrew is Director of R&D in Innovation at BTG. He specialises in the development of advanced biomedical polymer systems, for instance, to enhance the biocompatibility of implants or to modulate delivery of active agents in the body. These technologies have been applied to novel drug-device combination products for use in interventional therapies in the treatment of cardiovascular disease and cancer. He has published ~200 papers (H-index 46), 11 book chapters and 50 patent families/applications in the fields of polymers, biomaterials and drug delivery. He was recently awarded the Chapman Medal for distinguished research in the field of biomedical materials.

Abstract:

The practice of embolisation of blood vessels (deliberate occlusion of the lumen of the vessel to stem blood flow) has been practised by Interventional Radiologists for many decades. Guidewires and catheters are manouevered under X-ray image-guidance to target sites in the body where particles are then administered into the vessels create a bloackade. A wide variety of particulate embolic agents have been used over the years, many of which are commercially available and consist of different materials, shapes, size ranges and formats, all of which impact upon their clinical performance. The embolic can be temporary (biodegradable) or permanent in nature and can be made from natural or synthetic materials. Some of these embolic agents can contain and elute chemotherapeutic drugs or are inherenly radioactive in order to provide a locoregional treatment option for tunours due to the site-specific delivery of the particles. More recent advancements include particles that are visible under the standard X-ray techniques used to guide the interventions, enabling intra-procedural and post-procedural feedback with real-time visualisation of embolic particle localisation to help the physician optimise the treatment technique for improved clinical outcomes. In this presentation, an overview of different particulate agents will be provided together with a discussion on how the physicochemical properties of the biomaterials from which they are composed, influences their behaviour during handling and administration, flow and occlusion properties, tissue interactions and therapeutic delivery capability.

Speaker
Biography:

Dr. Youssef received his Ph.D. in Mechanical Engineering from University of California Los Angeles in 2010. Before joining SDSU, he was faculty member at California State University Northridge. His research is in the area of experimental mechanics of nontraditional materials, which include polymers, composites and smart materials. He is currently leading research on the application of composite materials in bioengineering, integration of smart materials in roughness control, and effect of environmental conditions on mechanical performance of protective polymeric coatings.

Abstract:

In the United States, the National Institute of Health estimated the economic impact of lower back pain to range between $19- and $71-billion per annum, where such pain has been associated with the degeneration of intervertebral discs. At advanced stages of degeneration, surgical intervention is required to alleviate the pain and allow patients to regain functionality for some of their daily activities. The focus of this research is to uncover the fundamental physical significance of the anatomical structure of the natural annulus fibrosus and its impact on the mechanical behavior of the annulus to resist common physiological loads. The approach was to focus the research on three consecutive phases. First, mechanics of engineering composite materials were used to predict the deformation resistance properties and failure behavior based on data available in the literature. Second, a new E-glass/PDMS composite laminate was manufactured using wet-layup processes, where the fiber volume fraction was set to 50% with the ability to be tailored based on the desired properties. Finally, Digital Image Correlation was integrated in a new experimental setup that applies uniform pressure on the internal surface of an E-glass/PDMS surrogate annulus. It was found that the predications using the constitutive relationship of orthotropic materials show good agreement with experimentally measured stiffness and failure strains. The newly proposed E- glass/PDMS material was also found to match the behavior of the native annulus, while being mildly anisotropic. Also, it provided the global properties of the biological structure.

Speaker
Biography:

Hugh is a Senior Manager within the Non-Clinical Development department at BTG. Within this role he oversees the planning and management of non-clinical and bio-analytical studies to assess the safety and efficacy of medical devices, which are then used to support the regulatory submission. He has over 15 years experience as a non-clinical study manager of GLP toxicology studies for the registration of pharmaceutical, veterinary, agrochemical and industrial materials.

Abstract:

Embolisation bead prototypes possessing significantly higher compression stiffness than commercially-available products were compared in vitro in a flowing glass-plate model to assess their penetration potential and bead size, not stiffness, was shown to be the influential factor. The comparative arterial distribution of prototypes in the 40-90 m and 70-150 m size range, together with commercially-available products (Embozene(TM)) was performed in a rabbit renal arterial embolisation model. Kidneys were embolised in 9 rabbits with beads of a particular size. Following embolisation of the second kidney with the comparator product, the animals were sacrificed and histologic evaluation performed. Three radial tissue slices, evenly distributed from the upper to lower poles, were sectioned from each kidney and stained with haematein-eosin-saffron. The pathology evaluation assessed: (a) The arterial distribution pattern in histology according to a division of the kidney in 5 zones of diminishing vessel diameter; (b) Diameter of the occluded vessels; (c) Number of beads present in occluded vessel sections; and (d) In vivo deformation of the beads. The model could clearly differentiate between the distribution patterns of beads of different sizes. Measurements of the diameter of occluded vessels highlighted that in all cases, the smaller bead sizes occluded more distally than larger beads. In addition, this model allowed for a comparison between beads of different stiffness but similar diameter and supported the in vitro data from the glass plate model that size and not stiffness was the biggest influence on depth of penetration and distribution.

Speaker
Biography:

Oscar Carvalho born and lives in Portugal. Obtained from the University of Minho Degree in Physics and Chemistry, MSc in Chemistry, MSc in Mechanical Engineering and postgraduate in Management. Obtained the PhD in Mechanical and fatigue properties of sintered Nanotube-based functionally graded materials on same institution . Have scientific professional experience on research in the mechanical engineering, materials, and chemistry at the University of Minho and it is currently participating in the project "Multi-laser sintering materials for the production of Functional Graded Structures". It is also invited professor at the University of Minho and is post doc member of Centre for Micro-Electro Mechanical Systems (MEMS) University of Minho, Portugal.

Abstract:

Although titanium and titanium alloys are the materials most often used in dental implants, mainly due to mechanical properties and biocompatibility, ceramics are becoming very attractive as new materials for this area. Zirconia seems to be a suitable dental implant material once it can overcome the main drawbacks of titanium implants, like metallic coloration, corrosion and in some cases, the cause of allergies. Zirconia seems also be more biocompatibility and avoids some problems found in titanium implants like autoimmunity and cellular sensitization and due to continuous scientific research, ceramic’s mechanical strength is improving, becoming more feasible for dental implants. Like titanium, Zirconia does not stimulate bone regeneration around the implant, due to its bioinertness. In this context, this work is focused in the development of Zirconia substrates doped with hydroxyapatite (HA) in order to promote earlier and stronger fixation. The substrates were prepared with laser CO2 laser to create cavities, where HA was then introduced, being afterwards sintered by the action of the same laser. This techique brings a huge advantage in materials processing, once by controlling the laser path; velocity and power it is possible to obtain cavities (patterning/machining) and also sinter different materials over the surface and cavities (Selective laser sintering / melting). Results showed that the cavities, roughness and laser power influence the adhesion and degradation of HA.

Speaker
Biography:

Dr. Ankush Anand is an Assistant Professor in the School of Mechanical Engineering at the Shri Mata Vaishno Devi University, Katra, J&K, India. Dr. Anand obtained Ph.D in 2011 with research work published in ASME. His basic research area is Design Through Life Cycle Engineering and he has published extensively in this area.Dr. Anand is also carrying out research investigations in the area of biotribology and biomaterials sustainable design though Tribology. He has also presented his research work in Conferences abroad which include ASME/STLE joint Tribology conference (USA).He has also reviewed research papers and was a session chair in conference abroad.

Abstract:

This research article presents a holistic approach for evaluating and selecting biomaterials from and among the variety of materials available. Biomaterials selection has become a major thrust area for designers and tribologists during the past few decades. The procedure proposed in this article helps in evaluation and ranking of biomaterials used for various application areas. The factors which influence the performance of system are identified and are called biomaterial factors. These factors of a biomaterial are expressed by means of a biomaterial graph. The graph is represented by a one-to-one matrix of the biomaterial factors. A procedure is developed for evaluating and comparing two biomaterials. The procedure is not only useful for selection and evaluation of biomaterials at operational stage, but can also be used for the design and development of a biomaterial at conceptual design stage from the biotribology point of view. The procedure is illustrated by means of an example.

Speaker
Biography:

Marcus is an Innovation Scientist at BTG. Initially focusing on analytical method development and validation, he is currently completing a part-time PhD with the University of Southampton in Applied Biomimetic Microfluidics and focusing on the application of this project to advancing treatment in the field of interventional oncology and pulmonology.

Abstract:

The primary purpose of Trans-Arterial Chemoembolization (TACE) is to restrict blood supply to hyper vascularised tumours whilst delivering a chemotherapeutic drug in a localised, consistent and efficacious regimen. Clinical opinion is divided regarding the primary mode of action: physical embolic or controlled drug release. Both the use of ethiodized oil emulsions mixed with doxorubicin (conventional cTACE) and ionically loaded Drug-Eluting Beads (DEB-TACE) provide proven clinical efficacy. Recent developments in emulsion stabilisation have posed the question of whether the safety of reduced systemic drug exposure provided by DEB could be combined with oil emulsions to provide a therapeutic benefit in patients. In a study conducted by Takayasu et al. n=11,030 patients treated with oil emulsions vs. emulsions and particulates presented an overall survival benefit in the particulate combination therapy[1]. This study evaluates novel radiopaque DEB in combination with oil emulsions using in vitro – in vivo flow distribution, drug release profiles and physiochemical stability. Bead-stabilised emulsions were easily prepared and doxorubicin loading into the DEB was rapid. In vitro DEB emulsions exhibited enhanced physical embolic abilities with slower drug elution kinetics vs. c-TACE. In vivo VX2 tumour model confirmed low systemic doxorubicin, anti-tumour activity and CT imaging at 7 days clearly showed oil droplets remaining throughout the liver lobe and targeted arteries filled with radiopaque beads. Fluroscopy in a porcine hepatic arterial and in vitro vascular flow model indicated comparible flow characteristics during administration to that of c-TACE.

Ing-Hong Ooi

International Medical University, Malaysia

Title: Folate-conjugated star branched PLLA-b-(PEG)2 copolymer as nanocarrier for targeted delivery

Time : 13:05-13:30

Speaker
Biography:

Ing-Hong Ooi obtained his PhD in 1998 from the University of Akron, Ohio, USA. He is currently a head of the department of Pharmaceutical chemistry and senior lecture in the school of Pharmacy, International Medical University, Kuala Lumpur, Malaysia

Abstract:

Folate-conjugated star-branched poly(L-lactide)-block-[poly(ethylene glycol)] copolymer are of interest as tumor-specific drug delivery system, targeting cancerous tumors overexpressed with folate receptors via receptor-mediated cellular uptake mechanism.The primary objective of this study was to synthesis and characterize folate-conjugated four-arm star-branched PLLA-b-(PEG)2 copolymers. The 4-arm star-branched copolymers with folate groups attached to the PEG chain ends were synthesized by a multi-step procedure using ring-opening polymerization and carbodiimide chemistry strategies. Briefly, in the first step, four-arm star branched PLLA was synthesised by a ring-opening polymerization of L-lactide in the presence of pentaerythritol as initiator and 4-dimethylaminopyridine DMAP/DMAP HOSO2CF3 as catalyst. The resulting polymer was activated with 4-nitrophenyl chloroformate (4-NPC), which was then reacted with aminoadipic acid (AAA) to afford AAA-terminated four-arm PLLA (P1). α-amino-ω-Folate-PEG was conjugated to P1 via carbodiimide chemistry to produce the title star-branched PLLA-b-(PEG)2 copolymer (P2). All synthesized polymers were precipitated in diethyl ether/methanol mixture followed by centrifugation and then purification by membrane dialysis against deionized water, using Spectra/Por membrane of appropriate molecular weight cut-off size, before being freeze-dried. FTIR and 1H NMR and GPC techniques were used to characterize and confirmed the synthesised intermediates as well as the target polymer P2. The nanoparticles of P2 loaded with a model drug were fabricated by using a modified emulsion solvent evaporation technique. The resulting nanoparticles average sizes ranged from 178-211 nm, with PDIs from 0.121 to 0.235, and zeta potentials from -13.2 to -19.9 mV before and after freeze drying. The drug release and cytotoxicity studies of the nanoparticles will be presented.

Break: Lunch Break 13:30-14:20

Theoni K. Georgiou

Imperial College, London

Title: Thermoresponsive triblock copolymers as injectable gels

Time : 14:20-14:45

Speaker
Biography:

Theoni obtained a BSc in Chemistry from the University of Cyprus in 2001, followed by a PhD in 2006 in Polymer Chemistry She then worked as a Postdoctoral Fellow with Professor Antonios G. Mikos at the Department of Bioengineering at Rice University in the USA. In October 2007, after she was awarded an RCUK Academic Fellowship, she moved to UK to join the Department of Chemistry at the University of Hull. In January 2014 she joined the Department of Materials at ICL. Her research interests involve synthesis and characterisation of polymers and their evaluation in a variety of biological applications.

Abstract:

Thermoresponsive polymers i.e. temperature-responsive polymers can be used an injectable gels in tissue engineering because they have the ability to in-situ encapsulate stem cells. Thus a scaffold can be created in the body without using invasive surgical techniques to implant it. The gelation point i.e.e the temperature that the gel is been informed is critical and need to be controlled well in order for the polymers to be applicable for this application. In our group we have synthesised and characterised a variety of thermoresponsive multiblock copolymers where the structural parameters (molar mass, composition, architecture and chemistry) were systematically varied to mainly investigate how the gelation point is affected by these structure parameters. T The optimum molar mass was found to be around 7000 g/mol and the optimum hydrophobic content around 35 wt%. Interestingly the position of the block within the polymer, thus the polymer architecture also influenced the thermoresponsive, sol-gel transition of the polymer. Specifically it was demonstrated that when the hydrophobic block is in the middle that results in a more clear and sharp sol-gel transition. In summary we were able to prove that the sol-gel transition and the gelation temperature can be tailored that is essential for the application by tailoring the structural properties of the polymer.

Speaker
Biography:

Andrew is Director of R&D in Innovation at BTG. He specialises in the development of advanced biomedical polymer systems, for instance, to enhance the biocompatibility of implants or to modulate delivery of active agents in the body. These technologies have been applied to novel drug-device combination products for use in interventional therapies in the treatment of cardiovascular disease and cancer. He has published ~200 papers (H-index 46), 11 book chapters and 50 patent families/applications in the fields of polymers, biomaterials and drug delivery. He was recently awarded the Chapman Medal for distinguished research in the field of biomedical materials.

Abstract:

We have taken human mesenchymal stem cells (hMSCs) that have been genetically engineered to produce Glucagon-like Peptide-1 (GLP-1) fusion peptide and encapsulated them within an alginate microcapsule to provide immunoprotection (CellBeads). The CellBeads were evaluated in a range of models of cardiovascular disease in order to ascertain if the implanted cells could illicit a beneficial therapeutic effect through the secretion and localised release of paracrine factors from hMSCs. In models of Acute Myocardial Infarction (AMI), CellBeads were infused intraarterially, in either a swine embolisation model of left ventricular dysfunction [1], or balloon occlusion models of moderate and severe acute myocardial infarction, with histological analyses and effects on functional recovery compared with relevant controls [2,3]. In a model of Vein Graft Disease (VGD), CellBeads were applied periadventially around a swine vein-into-artery interpositon graft and the effect on neointiamal formation and adventitial angiogenesis evaluated [4]. To evaluate potential application in Critical Limb Ischemia (CLI), the therapeutic activity of perivascular transplantation of CellBeads was assessed in an immunocompetent mouse model of limb ischemia [5]. In each of the models, implantation of the CellBeads was associated with notable functional improvement due to sustained delivery of locoregional paracrine factors secreted from the hMSCs, that supports the potential use of the technology in treatment of these disease states. Moreover, in each case there was an additional statistically significant increase in new blood vessels formation. This was identified as a consequence of Vascular Endothelial Growth Factor A (VEGF-A) secretion from the hMSCs.

Break: Lunch Break
Speaker
Biography:

Alice Hagan is a scientist at Biocompatibles UK Ltd and in her 2nd year studying for a PhD at the University of Brighton. Her research focuses on novel drug-device combinations for the treatment of liver tumours. In 2014, Alice was awarded an industrial fellowship from the Royal Comission for the Exhibition of 1851, in order to pursue her research and development of drug-eluting bead products in partnership with Biocompatibles.

Abstract:

DEBs are embolic agents that can be loaded with anti-cancer drugs, which are subsequently released over time at the tumour site following administration into the arteries that feed liver malignacies, using a technique known as transarterial chemoembolisation (TACE). The most commonly loaded drugs into DEB are doxorubicin and irinotecan, both cytotoxic agents that interfere with DNA replication. However, it is also possible to load DEB with certain targeted agents such as TKIs. Due to the chemical structure and properties of these compounds, it is necessary to use different methodological approaches to incorporate them into the bead matrix. We describe the loading of DC Bead™ with vandetanib, an antiangiogenic multi-targeted TKI. The molecule may exist in several pH-dependent charge states, which affects both its solubility in water and capacity to occupy drug binding sites within the beads. Maximum drug loading capacity of vandetanib into DC Bead™ and a novel radiopaque version was investigated at varying pH. Uniform distribution of the drug throughout the bead was confirmed by SEM-EDX analysis. The effect of drug loading on physicochemical properties of the beads such as size, radiopacity and compressibility was examined, as well as the characteristics of in vitro drug release. In order to mimic ischaemia after embolization, the effect of vandetanib on HepG2 cell viability under hypoxic conditions was investigated by MTT assay. Vandetanib showed equipotency in hypoxia and normoxia across a range of concentrations, with an IC50 of approximately 6.25µM, confirming its suitability for delivery from a DEB.

Speaker
Biography:

David A. Roberson, Ph.D. is an Assistant Professor in the Department of Metallurgical and Materials Engineering at The University of Texas at El Paso. He currently directs the Polymer Extrusion Lab in the W.M. Keck Center for 3D Innovation where he performs research related to the development of novel polymer matrix composites and polymer blends for additive manufacturing applications. Prior to his academic career, Dr. Roberson spent eight years working as an engineer in the semiconductor industry for Intel Corporation (2001-2006) and Qimonda NA (2006-2009). Dr. Roberson earned his B.S. in Metallurgical and Materials Engineering (1999), his M.S. in Metallurgical and Materials Engineering (2001), and his Ph.D. in Materials Science and Engineering (2012) from The University of Texas at El Paso.

Abstract:

The plant-derived biopolymer, polylactic acid (PLA) has experienced a rapid growth in the area disposable food container applications due to its biodegradability. In the area of consumer-grade 3D printing based on fused deposition modeling (FDM) technology, PLA is rapidly becoming the material of choice due in part to its perceived safety as compared to acrylonitrile butadiene styrene (ABS). As is the case with many other polymers, the applicability of PLA is hindered due to restrictions related to the physical properties of the material. The work presented here explores the modification of PLA through the addition of sustainable additives. Retaining compatibility with 3D printing systems while at the same time augmenting the physical properties of the biopolymer is addressed. Materials characterization of the novel PLA-based composites involving mechanical testing and fractography carried out through scanning electron microscopy (SEM) with be used to understand the effect of the additives on physical strength and failure modes. The effect of additives on biodegradability of 3D printed test coupons will also be presented.

Speaker
Biography:

Prof. Dr. Farah Kanwal obtained her Master degree in Chemistry from Punjab University in 1989. She earned her Ph.D (Polymer, Physical Chmeistry) from Strathclyde University, Glasgow, UK in 1995. She joined Govt. College University in 2000. She joined the Institute of Chemistry in 2004 as an Assistant Professor and presently serving as Professor of Physical Chemistry. She has published more than 50 research papers in the Journals of international repute. Major areas of her research interests are: Synthesis and characterization studies of polymers, polymer blends, conducting polymers, biopolymers, composites and nano-composites, polymer degradation, adsorption studies of dyes on polymer composites.

Abstract:

Nickel ferrite, NiFe2O4 nanoparticles (NFNPs) have been synthesized by chemical co-precipitation method. To enhance biomaterial potential of nickel ferrite NPs, their surface was tuned with biocompatible food grade polysaccharide polymer called glucomannan. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and thermal gravimetric analysis (TGA) were used to probe the effect and nature of coating on surface of nickel ferrite NPs. The surface morphology and dispersion of native and coated NFNPs was studied by scanning electron microscope (SEM), atomic force microscopy (AFM) and dynamic light scattering (DLS) respectively. Vibrating Sample Magnetometer (VSM) studies reveals that no particular effect of coating was observed on magnetic saturation (Ms),76.22 emu/g and ferromagnetic behaviour of NFNPs. Cell culture studies are exhibiting the less cytotoxicity mode of glucomannan coated NFNPs(NFNPs-Glu) over uncoated ferrite nanocrystals when tested against Chinese hamster ovary (CHO) cell line upto 2.2 mg/ml. The non-toxic, monodisperse, magnetic and biocompatible behaviour of glucomannan modified NFNPs make them a promising candidate for biomaterial applications as a contrast agent in magnetic resonance imaging (MRI) and drug delivery.

Speaker Slot Available

biomaterials@insightconferences.com

Title: Contact Program Co-ordinator: Vivian Elizabeth
Speaker
Biography:

Biography: Biography in a narrative manner in not more than 100 words

Abstract:

Abstract: Research abstract in not more than 300 words

Speaker Slot Available

biomaterials@insightconferences.com

Title: Contact Program Co-ordinator: Vivian Elizabeth
Speaker
Biography:

Biography: Biography in a narrative manner in not more than 100 words

Abstract:

Abstract: Research abstract in not more than 300 words

Speaker
Biography:

Marcus is an Innovation Scientist at BTG. Initially focusing on analytical method development and validation, he is currently completing a part-time PhD with the University of Southampton in Applied Biomimetic Microfluidics and focusing on the application of this project to advancing treatment in the field of interventional oncology and pulmonology.

Abstract:

In vitro biomimetic models have become increasingly utilised in the evaluation of medical devices over the last 30 years. Application in the field of Interventional Oncology for modelling purposes has been limited by the complexity of recreating biological vascular systems. Interventional Oncology and specifically embolisation, varies significantly in terms of its administration methodology. The specific process of blocking the primary blood supply to a hyper-vascularised tumour is anything but simple in terms of reproducibility and translation between patients, clinics and devices. Flow properties of drug-loaded embolic microspheres have been shown to influence the distribution, contact diffusion and spatial drug elution kinetics within tumours [1]. Moreover, variations in the administration style of the physician have been shown to play a significant part in the intra-tumoural distribution [2]. To model the unique flow properties of various embolic products, novel in vitro microfluidic test systems have been developed. Through compartmentalised recreations of clinical conditions, it becomes possible to predict and evaluate relevant flow properties prior to use in vivo. This presentation will analyse the effect of channel flow rate (Reynold’s number) and embolic size of doxorubicin loaded DC Bead™ 70-150µm and 100-300µm within in vitro flow channels of sizes representative of distal hepatic microvasculature. The effect of whole bead distribution is considered as a vehicle for distal drug distribution utilising clinically representative injection volumes for modelling bolus effects. A significantly higher dose (p=0.017) is observed in smaller flow channels with 70-150µm vs. 100-300µm trending with increased flow rates.

  • Track-17: 3D Printing of Biomaterials

Session Introduction

Speaker Slot Available

biomaterials@insightconferences.com

Title: Contact Program Co-ordinator: Vivian Elizabeth
Speaker
Biography:

Biography: Biography in a narrative manner in not more than 100 words

Abstract:

Abstract: Research abstract in not more than 300 words

Speaker
Biography:

Don has more than 30 years’ experience working in blue chip organisations holding senior scientific posts in ICI, Zeneca, Avecia and Polymer Laboratories. More recently he founded Chromatide where he worked as Chief Scientific Officer for 3 years and is credited as the sole inventor of all of the company's intellectual property. In 2009 he founded his second company, Spheritech which has already established a strong IP portfolio. Don is an internationally recognised authority on peptide synthesis, polymer design and chromatography. He is the author of numerous texts and book chapters and is the author of 'A Practical Handbook of Preparative HPLC'. With a track record of innovation he is the main inventor on 19 patents and the sole inventor on all patents filed by SpheriTech to-date. Apart from the inventive nature exemplified by published intellectual property Don has been instrumental in the concept, design, building and launch of equipment for batch-wise and continuous flow based solid phase synthesis over the last two decades. More recently Don has introduced new concepts in biotechnology based applications of continuous reactors which will be published in due course.

Abstract:

Tissue engineering is a relatively new tool available to scientists, first appearing in the early 1990’s (1). It was originally conceived as a potential solution to the lack of availability of donor organs and is now also additionally considered as an alternative strategy to animal testing for drug and chemical safety models. A three dimensional (3D) scaffold provides a support for cellular growth in such a way that specific cells form a 3D matrix of tissue which in turn can be transplanted into a patient to allow regeneration of the specified region. Spheritech have developed a novel biopolymer which has found many applications, amongst them is the formation of self-assembled macroporous biodegradable constructs specifically designed to support 3D cell culture. The porosity of the biopolymer is controlled by self-assembly in such a manner as to accommodate cell and nutrient penetration within. The unique features of the 3D cell culture scaffold developed by the company include the fact that it is composed entirely of naturally occurring components. The main backbone of the polymer is poly-ε-lysine which is an edible, non-toxic material currently manufactured on multi-ton scale and used predominantly as a preservative in foodstuffs. Poly-ε-lysine can be readily cross-linked with any multi-functional carboxylic acid and in particular we have found that the naturally occurring bis-carboxylic acids such as sebacic acid and dodecanedioic acid impart advantageous properties on 3D scaffolds. Ultimately the polymer is susceptible to degradation by protease activity to produce lysine and the fatty acid.

Speaker
Biography:

Anand Ramamurthi, PhD is Associate Professor of Molecular Medicine and Biomedical Engineering at the Cleveland Clinic. His research program is focused on developing biomimetic technologies and nanomedicine approaches for regenerative repair of ECM/elastic matrix, in vitro, and at sites of proteolytic disease. He is a Fellow of the American Heart Association (AHA) Council on Basic Cardiovascualr Sciences, and serves as editor/editorial board member of several tissue engineering/ regenerative medicine journals. He has 50 journal publications, several book chapters, is the author of a book on elastin regeneration and is the recipient of extramural research funding from the NIH, NSF, AHA, and other foundations.

Abstract:

Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to chronic breakdown of matrix proteins, such as elastin, via an overexpression of matrix metalloproteases (MMPs), specifically MMP-2 and -9. Auto-regenerative repair of disrupted elastic matrix by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents buildup of new, intact elastic matrix to enable AAA growth arrest or regression to a healthy state. Oral doxycycline (DOX) therapy can inhibit MMPs to slow AAA growth, it has systemwide side-effects and inhibits new elastin deposition within AAA tissue, diminishing prospects for restoring elastin homeostasis and thus arresting/regressing AAA growth. We have thus developed cationic amphiphile (DMAB)-modified nanoparticles (NPs) that unqiuely exhibit pro-elastogenic and anti-proteolytic properties, independent of the encapsulated drug for localized, sustained DOX delivery within AAA tissue at a much lower dose, that we have recently found to augment elastin regenerative repair. To provide greater specificity of NP targeting, we conjugated the DOX-NP surface with an antibody against cathepsin-K, a lysosomal protease that is highly overexpressed within AAA tissue. We determined conditions for efficient cathepsin-K Ab conjugation onto the NP surface, demonstrated improved NP binding to aneurysmal SMCs, the lack of changes to DOX release, and improved pro-elastogenic and anti-proteolytic effects of the cathepsin-K Ab-conjugated DOX-NPs due to improved NP-cell interactions. Ex vivo perfusion studies also indicated significantly greater binding of the modified NPs to the wall of matrix-disrupted porcine aortae. This study has shown that Cathepsin K Ab conjugation is a useful targeting modality for our pro-regenerative NPs. Future studies will investigate NP targeting to the AAA wall in rat model following intravenous or catheter-based infusion to a flow occluded aorta and their efficacy for induced regenerative matrix repair for AAA growth arrest.

Speaker
Biography:

Maria Tomoaia-Cotisel has completed PhD from Babes-Bolyai University (BBU) and postdoctoral studies from London University, King’s College, UK. She was the visiting scientist at Philipps University of Marburg, Germany, State University of New York at Buffalo, US, National Institutes of Health, and Molecular/Structural Biotech., Inc., Bethesda, MD, US. She is the director of Physical Chemistry Center, at BBU. She published over 240 original research papers, 5 patents, and 10 books in physical chemistry, including thermodynamics, chemical structure, biophysics, bionanomaterials, colloids and interfaces. She got awards, Gheorghe Spacu (Academy of Sciences, Romania), Alexander von Humboldt (Germany), Promotion of Science and Technology (Japan Society), Fogarty Award (US).

Abstract:

Innovative nano sized hydroxyapatite: HAP, modified HAP with Si, Mg and Zn: HAP-Si- Mg-Zn, and functional scaffolds of these materials with collagen:COL represent the first report on the effects of Si, Mg and Zn, simultaneously present within the layered ceramic scaffolds in human osteoblasts culture. The 14 scaffolds were manufactured by self-assembling layer by layer technique and fully characterized by XRD, FTIR, FT-Raman, TEM, SEM, and AFM. Scaffolds were tested in cell culture for adhesion and bioactivity of osteoblasts, which were cultivated for different times on scaffolds. For this goal, the cellular expression of osteoblasts markers: like collagen, osteopontin and osteocalcin were visualized by fluorescence microscopy and by using immuno-cytochemical staining methods. The data indicate that the combined scaffolds made of nanoHAP/COL, nanoHAP-Si/COL and nanoHAP-Si-Mg-Zn/COL layers have an improved stimulating activity to osteoblasts compared with native scaffolds (e.g., made only from nanoHAPs), particularly in promoting the formation of mineralized bone matrix. Moreover nanoHAP-Si-Mg-Zn/COL combined layered scaffolds substantially enhanced osteoblasts activity and adhesion, as evidenced by cell expression of collagen, osteopontin and osteocalcin as well as of F-actin stress fibers, in vitro. Thus, the current study clearly demonstrated that the incorporation of Si, Mg and Zn within HAP could be an active, safe and inexpensive tool for new HAPs development with potential clinical applications in orthopedic surgery, bone cancer therapy and nanomedicine.

Speaker
Biography:

Doctor Dora Alicia Cortés-Hernández works at CINESTAV-México, is a member of the National System for Professors has published 85 papers in indexed journals and 100 papers in proceedings. He has supervised and graduated 14 PhD students and 12 MSc students. The research areas of interest are bioactive ceramic systems, antibacterial materials, magnetic nanoparticles and biomimetic coatings.

Abstract:

Magnetic nanoparticles (MNP’s) of iron oxide and other transitions elements are ideal candidates for their use in biomedical areas as contrast agents in magnetic resonance imaging (MRI) and thermoseeds for magnetic hyperthermia treatment. In this work, MNP’s of MnxGa1-xFe2O4 (x= 0-1) were synthesized by sol-gel method using citric acid as chelating agent of metallic precursors. The synthesized powder was identified by X-Ray Diffraction as an inverse spinel structure of Fe1.4Ga1.6O4 where the substitution of manganese ions was observed by slightly reflexions displacements on the diffraction patterns. Magnetization saturation values obtained for the synthesized samples were in the range within 14.2 and 53.7emu/g, while the coercivity field was below 67 Oe in all cases. Transmission Electronic Microscopy allowed the determination of the particle size, which was around 18 nm. Magnetic induction results showed an efficient temperature increase of the nanoparticles under a magnetic field and quantities of 4.5mg of MNPs per mL of liquid medium are enough to increase the temperature at 43.5°C in around 7min. Hemolysis was tested using suspensions of 3.0, 4.5, 6.0 and 10.0mg of magnetic material per mL of solution and the results showed hemolytic values below 2% in all the cases. According to the results discussed above it is expected that these synthesized nanoparticles can be potentially used as thermoseeds for cancer treatment by hyperthermia therapy.

Speaker
Biography:

Dr. Madhu Gupta is a Research associate in Shri RawatPura Sarkar Institute of Pharmacy, Datia. She has about 10 years of research experience and teaching experience. She is pioneer scientist in the field of nanotechnology and drug delivery field. She has judiously exploited bioligands for targeting of bioactives and drug moiety. She has over 30 research publications to her credit published in journals of high scientific impact and contributed 08 chapters in various renowned books and to several international and national books.

Abstract:

Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by confocal laser scanning microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

  • Track-10: Tissue Engineering and Regenerative Medicine
    Track-7: Biomaterials and Nanotechnology
Speaker

Chair

Anand Ramamurthi

Cleveland Clinic, USA

Speaker

Co-Chair

Dora Alicia Cortes Hernandez

CINVESTAV-Mexico, USA

Speaker
Biography:

Anand Ramamurthi, PhD is Associate Professor of Molecular Medicine and Biomedical Engineering at the Cleveland Clinic. His research program is focused on developing biomimetic technologies and nanomedicine approaches for regenerative repair of ECM/elastic matrix, in vitro, and at sites of proteolytic disease. He is a Fellow of the American Heart Association (AHA) Council on Basic Cardiovascualr Sciences, and serves as editor/editorial board member of several tissue engineering/ regenerative medicine journals. He has 50 journal publications, several book chapters, is the author of a book on elastin regeneration and is the recipient of extramural research funding from the NIH, NSF, AHA, and other foundations.

Abstract:

Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to chronic breakdown of matrix proteins, such as elastin, via an overexpression of matrix metalloproteases (MMPs), specifically MMP-2 and -9. Auto-regenerative repair of disrupted elastic matrix by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents buildup of new, intact elastic matrix to enable AAA growth arrest or regression to a healthy state. Oral doxycycline (DOX) therapy can inhibit MMPs to slow AAA growth, it has systemwide side-effects and inhibits new elastin deposition within AAA tissue, diminishing prospects for restoring elastin homeostasis and thus arresting/regressing AAA growth. We have thus developed cationic amphiphile (DMAB)-modified nanoparticles (NPs) that unqiuely exhibit pro-elastogenic and anti-proteolytic properties, independent of the encapsulated drug for localized, sustained DOX delivery within AAA tissue at a much lower dose, that we have recently found to augment elastin regenerative repair. To provide greater specificity of NP targeting, we conjugated the DOX-NP surface with an antibody against cathepsin-K, a lysosomal protease that is highly overexpressed within AAA tissue. We determined conditions for efficient cathepsin-K Ab conjugation onto the NP surface, demonstrated improved NP binding to aneurysmal SMCs, the lack of changes to DOX release, and improved pro-elastogenic and anti-proteolytic effects of the cathepsin-K Ab-conjugated DOX-NPs due to improved NP-cell interactions. Ex vivo perfusion studies also indicated significantly greater binding of the modified NPs to the wall of matrix-disrupted porcine aortae. This study has shown that Cathepsin K Ab conjugation is a useful targeting modality for our pro-regenerative NPs. Future studies will investigate NP targeting to the AAA wall in rat model following intravenous or catheter-based infusion to a flow occluded aorta and their efficacy for induced regenerative matrix repair for AAA growth arrest.

Speaker
Biography:

Doctor Dora Alicia Cortés-Hernández works at CINESTAV-México, is a member of the National System for Professors has published 85 papers in indexed journals and 100 papers in proceedings. He has supervised and graduated 14 PhD students and 12 MSc students. The researche areas of interest are bioactive ceramic systems, antibacterial materials, magnetic nanoparticles and biomimetic coatings.

Abstract:

Magnetic nanoparticles (MNP’s) of iron oxide and other transitions elements are ideal candidates for their use in biomedical areas as contrast agents in magnetic resonance imaging (MRI) and thermoseeds for magnetic hyperthermia treatment. In this work, MNP’s of MnxGa1-xFe2O4 (x= 0-1) were synthesized by sol-gel method using citric acid as chelating agent of metallic precursors. The synthesized powder was identified by X-Ray Diffraction as an inverse spinel structure of Fe1.4Ga1.6O4 where the substitution of manganese ions was observed by slightly reflexions displacements on the diffraction patterns. Magnetization saturation values obtained for the synthesized samples were in the range within 14.2 and 53.7emu/g, while the coercivity field was below 67 Oe in all cases. Transmission Electronic Microscopy allowed the determination of the particle size, which was around 18 nm. Magnetic induction results showed an efficient temperature increase of the nanoparticles under a magnetic field and quantities of 4.5mg of MNPs per mL of liquid medium are enough to increase the temperature at 43.5°C in around 7min. Hemolysis was tested using suspensions of 3.0, 4.5, 6.0 and 10.0mg of magnetic material per mL of solution and the results showed hemolytic values below 2% in all the cases. According to the results discussed above it is expected that these synthesized nanoparticles can be potentially used as thermoseeds for cancer treatment by hyperthermia therapy.

Break: Coffee Break 11:20-11:45
Speaker
Biography:

Don has more than 30 years’ experience working in blue chip organisations holding senior scientific posts in ICI, Zeneca, Avecia and Polymer Laboratories. More recently he founded Chromatide where he worked as Chief Scientific Officer for 3 years and is credited as the sole inventor of all of the company's intellectual property. In 2009 he founded his second company, Spheritech which has already established a strong IP portfolio. Don is an internationally recognised authority on peptide synthesis, polymer design and chromatography. He is the author of numerous texts and book chapters and is the author of 'A Practical Handbook of Preparative HPLC'. With a track record of innovation he is the main inventor on 19 patents and the sole inventor on all patents filed by SpheriTech to-date. Apart from the inventive nature exemplified by published intellectual property Don has been instrumental in the concept, design, building and launch of equipment for batch-wise and continuous flow based solid phase synthesis over the last two decades. More recently Don has introduced new concepts in biotechnology based applications of continuous reactors which will be published in due course.

Abstract:

Tissue engineering is a relatively new tool available to scientists, first appearing in the early 1990’s (1). It was originally conceived as a potential solution to the lack of availability of donor organs and is now also additionally considered as an alternative strategy to animal testing for drug and chemical safety models. A three dimensional (3D) scaffold provides a support for cellular growth in such a way that specific cells form a 3D matrix of tissue which in turn can be transplanted into a patient to allow regeneration of the specified region. Spheritech have developed a novel biopolymer which has found many applications, amongst them is the formation of self-assembled macroporous biodegradable constructs specifically designed to support 3D cell culture. The porosity of the biopolymer is controlled by self-assembly in such a manner as to accommodate cell and nutrient penetration within. The unique features of the 3D cell culture scaffold developed by the company include the fact that it is composed entirely of naturally occurring components. The main backbone of the polymer is poly-ε-lysine which is an edible, non-toxic material currently manufactured on multi-ton scale and used predominantly as a preservative in foodstuffs. Poly-ε-lysine can be readily cross-linked with any multi-functional carboxylic acid and in particular we have found that the naturally occurring bis-carboxylic acids such as sebacic acid and dodecanedioic acid impart advantageous properties on 3D scaffolds. Ultimately the polymer is susceptible to degradation by protease activity to produce lysine and the fatty acid. This new scaffold is being developed for a range of applications including wound dressings, peripheral nerve repair, CNS repair, kidney repair, bone repair and cartilage repair, to name a few. The polymer and these applications will be discussed in detail.

Speaker
Biography:

Maria Tomoaia-Cotisel has completed PhD from Babes-Bolyai University (BBU) and postdoctoral studies from London University, King’s College, UK. She was the visiting scientist at Philipps University of Marburg, Germany, State University of New York at Buffalo, US, National Institutes of Health, and Molecular/Structural Biotech., Inc., Bethesda, MD, US. She is the director of Physical Chemistry Center, at BBU. She published over 240 original research papers, 5 patents, and 10 books in physical chemistry, including thermodynamics, chemical structure, biophysics, bionanomaterials, colloids and interfaces. She got awards, Gheorghe Spacu (Academy of Sciences, Romania), Alexander von Humboldt (Germany), Promotion of Science and Technology (Japan Society), Fogarty Award (US).

Abstract:

Innovative nano sized hydroxyapatite: HAP, modified HAP with Si, Mg and Zn: HAP-Si- Mg-Zn, and functional scaffolds of these materials with collagen:COL represent the first report on the effects of Si, Mg and Zn, simultaneously present within the layered ceramic scaffolds in human osteoblasts culture. The 14 scaffolds were manufactured by self-assembling layer by layer technique and fully characterized by XRD, FTIR, FT-Raman, TEM, SEM, and AFM. Scaffolds were tested in cell culture for adhesion and bioactivity of osteoblasts, which were cultivated for different times on scaffolds. For this goal, the cellular expression of osteoblasts markers: like collagen, osteopontin and osteocalcin were visualized by fluorescence microscopy and by using immuno-cytochemical staining methods. The data indicate that the combined scaffolds made of nanoHAP/COL, nanoHAP-Si/COL and nanoHAP-Si-Mg-Zn/COL layers have an improved stimulating activity to osteoblasts compared with native scaffolds (e.g., made only from nanoHAPs), particularly in promoting the formation of mineralized bone matrix. Moreover nanoHAP-Si-Mg-Zn/COL combined layered scaffolds substantially enhanced osteoblasts activity and adhesion, as evidenced by cell expression of collagen, osteopontin and osteocalcin as well as of F-actin stress fibers, in vitro. Thus, the current study clearly demonstrated that the incorporation of Si, Mg and Zn within HAP could be an active, safe and inexpensive tool for new HAPs development with potential clinical applications in orthopedic surgery, bone cancer therapy and nanomedicine.

Esra Altun

Marmara University, Turkey

Title: Production of a new bio-inspired neuro-regeneration structure

Time : 12:35-12:55

Speaker
Biography:

Esra Altun has completed her bachelor degree at the age of 22 years from department of Biology at Marmara University. She is a master student in Department of Metallurgical and Materials Engineering, Faculty of Technology at Marmara University. Also she is working at Advanced Nanobiomaterials Research Laboratory at Marmara University. She is interested in biology, biomaterials and nanotechnologic systems. At the present time she is working on Bacterial Cellulose and its applications.

Abstract:

Tissue application and regenerative medicine are the basis of engineering and life sciences to improve and repair tissue malfunctions. Functional disorders or loss of sensory and motor function of nerves are included in the research spectrum of tissue engineering with research and development intentions. Recently, Electrospinnig Technique is a rapid and facile duration driven by the electrical power on the surface of polymeric solution, fabricated of polymer nanofibers using an electrostatic force. Electrospinning provides non-wovens to the order of few nanometers with large surface areas, ease of functionalization for various purposes and superior mechanical properties. Cellulose is one of the most plentiful biopolymer found in nature but it can also be synthesized by several bacterial species. In this work, Acetobacter xylinum strain were used. Bacterial Celulose (BCs) is generally water-insoluble, flexible and elastic biopolymer with high tensile strength. Because of those features it has recently became quite popular in scientific researches. Despite previous studies, BCs has been dissolved in unique method within our study. In this study reported that BCs/PCL blend nanofibers were produced using electrospinning technique for replacement to unfunctional nerve tissue. SEM images, FTIR data and mechanical properties of BCs/PCL blend nanofibers with capsules were analyzed. It came to realization that fibers with capsules were branching just like the nerve systems of humans (NSHs). Process outgrowth as such would be a good material for design a new novel nerve cell therapy method (Neuroregeneration method) based on biomimic fundamentals and guide these nanocarrier fibers to where it is needed.

Speaker
Biography:

Xu Yuanhao has completed his BEng and MSc degree at City University of Hong Kong, and is now pursuing his PhD study at the same university. He is currently a member of Centre for Biosystems, Neuroscience, and Nanotechnology.

Abstract:

Natural killer (NK) cells serve an important role in immune system by recognizing and killing potentially malign cells without antigen sensitization, and could be important in cancer therapy. We have designed and fabricated microwell arrays with microchannel connections in polydimethylsiloxane (PDMS) substrates to study the interaction dynamics of NK-92MI cells with MCF7 breast cancer cells using time-lapse imaging by fluorescence microscopy for 15 h. Although cell seeding density is the same, NK cell cytotoxicity was found to be stronger in larger microwells, which is manifested as higher target death ratio (D=NMCF7 Death /NMCF7 Total) and shorter triggering time of first target lysis. Mirochannel connection between adjacent microwell of the same size increased the overall target death ratio by >10%, while connection between microwells of different sizes led to significantly increased target death ratio and delayed first target lysis in smaller mirowells as shown in Fig. 1. Our findings reveal unique cell interaction dynamics such as initiation and stimulation of NK cell cytotoxicity in a confined microenvironment, which is different from population-based study. The results could lead to a better understanding of the dynamics of NK cell cytotoxicity.

Break: Lunch Break 13:15-14:05
Speaker
Biography:

Luanda C Lins is currently a Fellow National Council for Scientific and Technological Development Researcher CNPq, Brazil and PhD Student at the National Institute of Applied Sciences, INSA, France. She has completed her Master's degree in Materials Science and Engineering from the Federal University of Santa Catarina and graduated in Bachelor in the Course of Chemistry and Chemical Technology at UFSC. The main focus of her interdisciplinary research is to develop advanced materials, especially polymers, for the controlled release of drugs and designing systems that sustain, enhance or direct the growth and differentiation of cells for the rapidly growing field of tissue engineering.

Abstract:

Electrospun piezoelectric fibers can be used in neural tissue engineering to mimic the physical, biological and material properties of the native extracellular matrix. In this study, we employed fibers scaffolds for the tissue engineering of the neuro-application. To study the role that three- dimensional scaffolds plays, a rotating drum collector was used to electrospun polyvinylidene difluoride (PVDF) fibers at various rotation speeds and the morphology, orientation, polymorphism and mechanical behavior of the non-aligned and aligned fibers were characterized. We found that the mechanical and columbic force by electrospinning of PVDF induced local conformation change to promote the β-phase. Neural stem cells (NSCs) were seeded on non-aligned and aligned scaffolds and cell morphology, survival and neuronal and glial differentiation were studied by microscopic techniques. We noted that specific degrees of scaffold anisotropy might represent a critical design feature in the fabrication of scaffolds. Our results showed that the survival of NSCs and the capacity of NSCs to differentiate in the neuronal and glial pathways depend on the degree of alignment of the fibers. These results demonstrate that piezoelectric fiber-aligned scaffolds may serve as instructive scaffolds for NSC survival and differentiation and may be valuable tools for the development of cell and scaffold based strategies for neural repair.

Speaker
Biography:

Shima Salmasi is a PhD student and research associate at the Centre of Nanotechnology and Regenerative Medicine, University College London. She completed her Master of Science in Nanotechnology & Regenerative Medicine and now, as part of her PhD, is researching on an innovative translational project with the aim of improving the current standards of spinal fusion surgery. This is a very interesting project with great potentials to provide a clinically effective solution to overcome the shortcomings of the currently available techniques of spinal fusion surgery using tissue engineering and nanotechnology.

Abstract:

As the majority of the biological reactions in human body occur on the surface or interference of a biomaterial or device, surface properties such as nanotopography can play critical role in determining the success of their implantation. As the result, the emerging fields of tissue engineering and regenerative medicine can greatly benefit from manipulation of nano-surface characteristics of implants and devices in order to guide and control the growth and differentiation of various cell types. For instance, it has been shown that the function of mesenchymal stem cells, multipotent stromal cells with the ability to differentiate to various cell types, could be regulated through physical interactions with specific nanotopographical cues such as surface roughness or stiffness. Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU), a new breed of novel nanocomposite material, developed by researchers at the University College London, has shown enhanced biocompatibility, superior mechanical engineering properties and augmented resistance. This novel polymer has already been successfully tested in vitro, in vivo and in human as a scaffold for bioartifical organs as well as a coating for medical devices. Here, we report of an investigation on the role of nano-surface characteristics of nanohydroxyapatite/POSS-PCU nanocomposite scaffolds for the purpose of bone tissue engineering. Our results indicate that by etching the surface of our scaffolds and/or introducing porosity, we are able to design surfaces with optimum roughness, stiffness and structure, which could then be used to guide and control cell attachment, growth and differentiation for the purpose of repairing or regenerating large bone defects.

Speaker
Biography:

Julian Dye graduated in Biochemistry from The University of Oxford and gained a PhD in Physiology from Imperial College London for work on human placental mcirovascular endothelial behaviour. He then worked for a research charity in the field of reconstructive plastic surgery, where he invented a novel pro-angiogenic synthetic dermal replacement, Smart Matrix. He took the project through development, scale-up and translation to clinical cleanroom manufacuture and pre-clinical evaluation and commercialisation. Julian then joined the Open University and recently moved to a lectureship at IBME Oxford, to pursue research on bio-intelligent scaffolds.

Abstract:

A novel solution has been developed for the unment clinical need for an effctive pro-angiogenic bio-intelligent biomaterial for reconstruction of skin loss wounds. Firstly the application of fibrin as a pro-angiogenic biomaterial was identified by 3D endothelial cell migration assays. A surgically feasible porous cross-linked fibrin-alginate biomaterial scaffold, Smart Matrix (SM), was formulated. Potential cytotoxicity was prevented by washing with a reducing agent, established by cytotoxicity and cell adhesion assays. Prototype material supported rapid ingress of endothelial cells in vitro. Engraftment of SM into porcine full thickness (FT) excision wounds demonstrated rapid vasculogenesis at 750 – 900μm depth from the wound bed over the first 7 days. The extent of celularisation and vascularisation in the FT model was maximised by optimisating formulation and manufacturing. Open porosity, 100μm pore diameter, enabled complete integration of 1mm thick material within 7d. This allowed a single step reconstruction with overgrafting of 150μm split-thickness skin graft. Resorption of the material takes 3-5wk which matches the rate of collagen deposition and remodelling. Wound contracture was around 35%, similar to refernece materials. The effect of SM was evaluated in a novel partial burn excision model of delayed wound healing. This demonstrated accelerated healing and switch from internal inflammatory granulation to exudatve regenerative neodermal tissue formation. This work exemplifies the value of such emergent strategies to develop bio-intelligent biomaterials. The approach has resulted in a vasculogenic bio-material which produces a non-fibrotic neodermis for full thickness skin reconstruction, with pre-clinical evidence of stimulating healing of delayed wounds.

Speaker
Biography:

Dr. Madhu Gupta is a Research associate in Shri RawatPura Sarkar Institute of Pharmacy, Datia. She has about 10 years of research experience and teaching experience. She is pioneer scientist in the field of nanotechnology and drug delivery field. She has judiously exploited bioligands for targeting of bioactives and drug moiety. She has over 30 research publications to her credit published in journals of high scientific impact and contributed 08 chapters in various renowned books and to several international and national books.

Abstract:

Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by confocal laser scanning microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

  • Track-11: Biomaterials for Therapeutic and Investigative Delivery
    Track-12: Biomaterials in Delivery Systems
    Track-4: Properties of Biomaterials
Speaker

Chair

Xiaohui Zhang

Lehigh University, USA

Speaker
Biography:

Xiaohui “Frank” Zhang received his doctorate in Physiology and Biophysics from the University of Miami in 2003. From 2004 to 2008, Dr. Zhang received his postdoctoral training at Harvard Medical School with Prof. Timothy A. Springer. Prior to joining the Lehigh faculty, he served as a principal investigator at the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences. His work has been published over 40 research articles in journals such as Science, Nature, and PNAS. Zhang’s research and teaching focus on the structural and biomechanical properties of proteins, protein engineering, biomechanics, physiology, and biophysics.

Abstract:

The large, multimeric plasma protein von Willebrand Factor (VWF) plays an essential role in capturing platelets onto the damaged vascular wall, allowing the initiation of blood clotting. VWF effectively senses blood flow, changing conformation in high flow from an inactive, compact globule to an elongated shape that allows VWF to interact with both platelets and damaged vascular wall. Although basic biological properties of VWF have been elucidated, little is known about the detailed biomechanical properties of vWF and how these properties dictate its structure and function in flow environments. We have adapted single-molecule force measurement approaches to study how mechanical aspects of VWF relate to its biological functions. Herein, we employed single-molecule optical tweezers to monitor in real time the structural stability of VWF. We demonstrated that the A2 domain of vWF unfolds in response to tensile force and exposes its Tyr842-Met843 scissile bond for cleavage by ADAMTS13, a metalloprotease found in the circulating blood. Such process provides an important mechanism to convert the highly thrombogenic, ultra large vWF multimers in blood shear to smaller multimeric forms and, consequently, to prevent overgrown thrombus. In addition, we have directly observed the force-induced conformational change in VWF that is essential for VWF’s activation under blood flow. Together, the study has revealed the biomechanical properties of VWF, with significant insight for the design of synthetic molecules based on VWF in pursuit of targeted drug therapies.

Speaker
Biography:

Marcus is an Innovation Scientist at BTG. Initially focusing on analytical method development and validation, he is currently completing a part-time PhD with the University of Southampton in Applied Biomimetic Microfluidics and focusing on the application of this project to advancing treatment in the field of interventional oncology and pulmonology.

Abstract:

In vitro profiling using microfluidic models has become increasingly utilised in the evaluation of medical devices over the last 30 years. To evaluate the unique flow properties of embolic products, bespoke in vitro microfluidic test systems have been developed. A traditional issue associated with angiographic guided administration of embolic products has been visualising real-time vascular positioning post-delivery. This issue has been addressed with the development of a novel radiopaque beads. The fundamental physiochemical properties of these novel embolic agents have been presented by Duran et al 2016 [1]. However the flow properties and user handling considerations have not been fully compared to non-radiopaque embolics in vitro. This presentation will focus on the characterisation of novel radiopaque microspheres and the profiling methods that have aided in their development. It will also cover the specific advantages provided clinically through extensive in vitro profiling of flow distribution, CT visualisation and deliverability studies compared to in vivo distribution data. The flow properties of RO Bead in terms of final distal location have been shown to be comparable to DC Bead™ under a variety of in vitro tests and in vivo models however physiochemical properties inherent to the radiopacity functionality have been shown to alter the compressibility, suspension and interchannel packing characteristics in vitro. These physical properties have not been shown to influence the in vivo physical penetration end-points, administration user response or distribution pattern of representative sizes of either embolic in vitro.

Speaker
Biography:

Tanya Swaine is a 2nd year PhD researcher at the University of Huddersfield, executing a project in coloboration with Biocompatibles UK Ltd. Prior to the commencement of her PhD, she gained five years industrial experience working with medical devices, before pursuing her interests at doctorate level. Prior to the completion of her first year in research, she had already published a paper in the well reputed international journal of pharmaceutics.

Abstract:

A novel flow through elution method mimicking embolization was developed to quantify drug elution from Drug-Eluting Beads (DEB). This study intends to overcome limitations of existing techniques and to provide more in vivo-like drug elution profiles for DEB evaluation. DEB of various sizes loaded with doxorubicin at clinically relevant concentrations were tested. The developed method used a temperature controlled continuous open-loop flow through extraction cell, through which the elution medium was driven by a peristaltic pump, and drug elution was monitored by a UV detector. Historically, elution rates have been generated largely on a closed-loop system, which are highly dependent upon the method and conditions used, making comparisons very difficult. USP II [1] and IV [2] methods offer comparative or quality control data due to rapid drug extraction and automation, whereas the T-apparatus [3] mimics the in vivo situation correlating to systemic exposure but has some practical limitations. Our method generates reproducible data, allowing more effective DEB elution over a practical time period. Elution remains faster the smaller the beads size but the difference in release rates is less pronounced than the other methods which are highly dependent on bead surface area exposure. This new method was used to characterize the elution of drug from a number of different DEB for comparison with published in vivo data and offered more clinically-relevant conditions than existing methods. It allowed for evaluation of various parameters (drug, extraction flow rate, size, geometry, novel DEB materials etc.) ultimately aiding in the development of more sophisticated products for the clinician.

Break: Coffee Break 16.25-16.45
Speaker
Biography:

Currently she is a fellow National Council for Scientific and Technological Development researcher (CNPq, Brazil - http://www.cnpq.br/), PhD student at the National Institute of Applied Sciences (INSA - https://www.insa-lyon.fr/en/) - France. She has master's degree in Materials Science and Engineering from the Federal University of Santa Catarina and graduated in bachelor in the Course of Chemistry and Chemical Technology at UFSC. The main focus of her interdisciplinary research is to develop advanced materials, especially polymers, for the controlled release of drugs, and designing systems that sustain, enhance, or direct the growth and differentiation of cells for the rapidly growing field of tissue engineering.

Abstract:

Electrospun piezoelectric fibers can be used in neural tissue engineering to mimic the physical, biological and material properties of the native extracellular matrix. In this study, we employed fibers scaffolds for the tissue engineering of the neuroaplication. To study the role that three- dimensional scaffolds plays, a rotating drum collector was used to electrospun polyvinylidene difluoride (PVDF) fibers at various rotation speeds, and the morphology, orientation, polymorphism and mechanical behavior of the non-aligned and aligned fibers were characterized. We found that the mechanical and columbic force by electrospinning of PVDF induced local conformation change to promote the β-phase. Neural stem cells (NSCs) were seeded on non- aligned and aligned scaffolds and cell morphology, survival and neuronal and glial differentiation were studied by microscopic techniques. We noted that specific degrees of scaffold anisotropy might represent a critical design feature in the fabrication of scaffolds. Our results showed that the survival of NSCs and the capacity of NSCs to differentiate in the neuronal and glial pathways depend on the degree of alignment of the fibers. These results demonstrate that piezoelectric fiber- aligned scaffolds may serve as instructive scaffolds for NSC survival and differentiation, and may be valuable tools for the development of cell-and-scaffold-based strategies for neural repair.

Speaker
Biography:

Dr. Beata Chertok is an Assistant Professor of Pharmaceutical Sciences and Biomedical Engineering at the University of Michigan, where she directs the Laboratory for ‘Remote and Image-Guided Therapeutics”. Beata Chertok received her Ph.D. from the University of Michigan and trained as an NIH/NIBIB Postdoctoral Fellow at the Massachusetts Institute of Technology. Her research expertise is in engineering advanced biomaterials at the nanometer and micrometer scales for targeted, image-guided and personalized drug delivery. Dr. Chertok is a recipient of multiple research awards including the MIT Cancer Center for Nanotechnology Excellence Award (2010), the NIH/NIBIB National Research Service Award for Postdoctoral Fellows (2012) and St. Baldrick’s Scholar Award in pediatric oncology research (2015).

Abstract:

Development of biomaterial-based carriers for drugs and genes is an exciting area of research at the interface of pharmaceutical sciences and biomedical engineering. Drug carriers are sought to encapsulate a drug cargo, protect it from elimination and degradation, and ferry it to the site of pathology, while minimizing potentially harmful detours to healthy organs. However, success in these tasks is at odds with the normal human physiology, which has evolved to eliminate harmful pathogens and xenobiotics. Although many “passive” drug carriers have been devised in an attempt to achieve targeted delivery of drugs and genes to diseased tissues, the mission of these carriers is often compromised by elimination mechanisms and multiple transport barriers obstructing their access to target cells. Our research focuses on development of “active” biomaterial drug platforms that combine sensitivity to external stimuli with visibility to medical imaging modalities. Such platforms can be externally activated on -demand to prevail over transport barriers at the site of pathology and non-invasively monitored to visualize arrival of carriers at the target site. In my talk, I will illustrate our strides in this domain through examples of magnetically- and acoustically-responsive and image-visible biomaterials we are currently developing. I will describe the process of implementing a biomaterial drug carrier with desired in vivo performance from an idea to material fabrication to proof-of-concept demonstration of functionality in animal models.

Speaker
Biography:

Dr. Omoruyi Idemudia is a post-doctoral fellow. He received the prestigious NRF/SIF innovation PDF award in 2014 and he is with the University of Fort Hare, South Africa. He obtained his BSc. Hons degree in Industrial Chemistry at the University of Benin, Nigeria. His research has involved but not restricted to the synthesis of compounds/materials with novel properties, their coordination with metal ions, identification and their biological studies. Omoruyi has co-authored over 15 research publications and have several conferences (international/national) attendance to his credit.

Abstract:

The development of new molecules (materials) with novel properties, having broad spectrum therapeutic activities that will become alternative medicinal drugs have attracted a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance to them and their toxicity effects among others. Also compounds containing metal centres (e.g cis-platin) have been employed for many years as therapeutic agents because of their biological activities, and as such synthesized organic/inorganic compounds are coordinated with metal ions in an effort to increase their potency. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have being well established. Through a condensation reaction with amines they form a more chelating and superior group of compounds known as azomethines. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with sulphanilamide to get a new sulphanilamide azomethine which was further reacted with palladium and platinum, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized/identified by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. The bidentate ON ligand forms a square planar geometry on coordinating with metal ions. Using the disc diffusion technique to screen the synthesized compounds at 20 mg/ml against selected bacterial isolates in triplicates, potential bactericides were identified. Their bioactivity vary, with the metal complexes showing higher antibacterial activity at an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to Ascorbic acid (standard drug).

Speaker
Biography:

Oladele Isiaka Oluwole has completed his PhD at the age of 43 years from Federal University of Technology Akure and he is still searching for a place to carry out postdoctoral studies. He is the Sub-Dean, School of Engineering and Engineering Technology, Federal University of Technology, Akure. He has published more than 40 papers in reputed journals.

Abstract:

This work was carried out to investigate comparatively the effects of carbonized and unmodified cow bone particles on the mechanical properties of polyester matrix composites in order to investigate the suitability of the materials as biomaterial. Cow bones were procured from an abattoir, sun dried for 4 weeks and crushed. The crushed bones were divided into two, where one part was carbonized by being burnt to ashes while the other part was pulverized with laboratory ball mill before the two grades were sieved using 75 µm sieve size. Bone ash and bone particle reinforced tensile and flexural composite samples were developed from pre-determined proportions of 2, 4, 6, and 8 %. The samples after curing were striped from the moulds and were allowed to further cure for 3 weeks before tensile and flexural tests were performed on them. The tensile test result showed that, 8 wt % bone particle reinforced polyester composites has higher tensile properties except for modulus of elasticity where 8 wt % bone ash particle reinforced composites has higher value while for flexural test, bone ash particle reinforced composites demonstrate the best flexural properties. The results show that these materials are structurally compatible.

  • Workshop on Direct Digital Manufacturing of Biomaterials
    Geoffrey Robert Mitchell
    Centre for Rapid and Sustainable Product Development
    Portugal
  • Poster Presentations

Session Introduction

Aurica P. Chiriac

Petru Poni Institute of Macromolecular Chemistry, Romania

Title: Strategy for polymer network preparation and ensuring intramolecular conditions for further coupling applications
Speaker
Biography:

Aurica P. Chiriac has completed her PhD in 1994. She has published more than 100 papers in reputed journals and she is member in editorial board of some reputed journals. She has participated in more than 15 Romanian Projects and 5 European Projects.

Abstract:

The synthesis of “smart” molecules is current areas of research as their specific functions can significantly improve their performance in various applications. This study is devoted to synthesis and investigations of poly(N,N dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) as “smart” macromolecular compound in order to evaluate the physico-chemical characteristics in terms of temperature and pH sensitive abilities, as well its rheological, dielectric and spectroscopic properties. The new system can be included into the “smart” polymer class owing to the gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability, biocompatibility, good films forming, pH sensitive response which is able for. This study evaluates the physiochemical characteristics of poly(N,N-dimethyl- acrylamide-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) (PDMA_U) in terms of temperature-sensitive abilities, rheological and dielectrical properties, for bringing useful information for further specific use of these compounds. The stereochemistry of the copolymer network ensures intramolecular strategies for further coupling processes and as well to become a multi-sensitive drug delivery system. In this context quercetin was imprinted into the polymer network and the antioxidant character of the new system was tested. The bio-compatibility was tested in vivo, and granuloma test in rats was performed correlated with the activity of enzymes involved in oxidative stress as well as immunologic effects of tested supramolecular complexes that include quercetin as therapeutic agent.

Speaker
Biography:

Aurica P. Chiriac has completed her PhD in 1994. She has published more than 100 papers in reputed journals and she is member in editorial board of some reputed journals. She has participated in more than 15 Romanian Projects and 5 European Projects.

Abstract:

The study reports the preparation of the new drug carrier gel system based on poly(itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) (PITAU) copolymer and hyaluronic acid (HA-PITAU). In relation with its composition PITAU has specific conformational structure owing to the unsaturated double bond of 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane comonomer and the spiroacetal moiety, giving macromolecular chains with network type structures. SEM microscopy and chemical imagining evidence the homogeneous porous structure of the new 3D network. NIR-chemical imaging technique prove the successful preparation of polymeric drug delivery system by using indomethacin (IND) as bioactive model substance. The dissolution data revealed the interdependence of the ratio between the two compounds and attaining optimum loading capacity. In vivo study demonstrated that HA_ PITAU and HA_ PITAU_IND determined similar blood parameters modifications and biochemical responses with distilled water, after intraperitoneal administration in mice. Systemic administration of the tested substances in mice did not modify their immune reactivity comparing with control group. All these results reveal a good in vivo biocompatibility. The bioactive compound caused a significant antinociceptive effect occurring after 60 minutes and lasts about 3 hours in tail flick test.

Speaker
Biography:

Giulia Neri obtained her Masters Degree in Pharmaceutical Chemistry and Technology from the University of Messina in 2013, where she is currently a PhD student in Chemical Sciences. Her work focuses on the development of new nanobioteranostic drug-delivery systems based on graphene nanomaterials and hyaluronic acid. At present she is working at the National Physical Laboratory (London, UK), on the development of peptide-based self-assembly systems for drug delivery.

Abstract:

Multifunctional nanoplatforms employed for active and passive tumor targeting represent important devices to overcome some of the critical issues related to the cancer therapy, such as the inherent limitations of drugs to cross anatomical and patho-physiological barriers, and to improve the specific drug delivery to tumor tissues. Graphene (G) and its multifunctional derivatives may offer passive targeting toward tumor sites, whereas hyaluronic acid (HA), that counts several specific receptors typically over-expressed on the surface membranes of various tumor cells, is the ideal component of multifunctional platforms for active targeting. Herein, we report the conjugation of Silibinin (Sil), the most active component of a complex of flavonoids contained into silymarin employed mainly as hepatoprotective agent but with application that goes beyond liver diseases and expands to cancer, to G-based and HA-based materials (Fig. 1). The biocompatibility of new platforms has been evaluated on Human Mesenchymal Stem cells and their anticancer effects have been studied on Human Osteosarcoma and Human Breast Cancer cell lines.

Speaker
Biography:

Anna Constantinou has obtained a BSc in Chemistry from the University of Cyprus in 2014 and an MSc in Advanced Materials Science and Engineering from Imperial College London (ICL). She is currently doing a PhD in Polymer Chemistry at the Department of Materials at ICL.

Abstract:

Thermo-responsive polymers which respond to the temperature by forming physical gels are popular candidates for 3-D printing. The sol phase facilitates the loading of the polymer-containing ink into the needle, whereas the gel phase contributes to the maintenance of the formed 3-D structure. In this project, thermo-responsive ABC triblock copolymers polymers were synthesised via group transfer polymerisation (GTP). The A, B, and C blocks were based on a poly(ethylene glycol) (PEG) methacrylate, n-butyl methacrylate (BuMA), and 2-(dimethylamino)ethyl methacrylate (DMAEMA). Three different PEG based monomers were used as the A block; di(ethylene glycol) methyl ether methacrylate, penta(ethylene glycol) methyl ether methacrylate, and nona(ethylene glycol) methyl ether methacrylate, which are abbreviated as DEGMA, PEGMA, and NEGMA, respectively. Systematic studies of the composition as well as the length of PEG side group were carried out. Three different compositions as well as three different PEG based monomers were used, resulting in nine ABC triblock copolymers. The molecular weight (MW) and the architecture were kept constant. Their values were determined by previous studies carried out by the group which showed that these parameters induce the clearest sol-gel transition. The effect of the PEG side group length and the composition on the thermoresponsive behaviour of the resulted polymers was investigated. Both parameters proved to affect the sol-gel transition. More specifically, the thermo-responsive behaviour was favoured by decreasing the PEG side group length and by increasing the hydrophobic content, as expected.

Hyun-Do Jung

Korea Institute of Industrial Technology, Korea

Title: Densified titanium implants embedded with BMP-2
Speaker
Biography:

Hyun-Do Jung has completed his PhD from Seoul National University and postdoctoral studies from Seoul National University. He is the senior researcher of Korea Institute of Industrial Technology, a premier national laboratory in Korea. He has published more than 15 papers in reputed journals and is now working on producing metal scaffold by 3D printing.

Abstract:

Titanium (Ti) and its alloys are used extensively for orthopedic and dental implants, owing to their good mechanical and biological properties. Recently, biomedical implants were improved osteoinductivity incorporating with growth factors such as bone morphogenetic proteins (BMPs). However, growth factors deposited on the implant surface are often easily released with a rapid burst. In this study, we fabricated BMPs-embedded titanium implants using new techniques and improve the potential for embedment of growth factors. For growth factor loading, porous Ti discs were soaked in BMP-2 in a vacuum and then air-dried. After drying, coated porous Ti discs were pressed by uniaxial press. The BMP-2 release test was performed in PBS at 37 °C for 90 days. In vitro test were monitored by MTS assay and ALP activity. After pressing, the Ti was well densified without any noticeable defects such as cracking or large voids. It should be noted that the porosity decreased as pressure increased and that the Ti was almost densified when the pressure reached to 1500 Mpa. The BMP-2 was coated in the inside of pores before pressing and released through micropores slowly. From the release kinetics it is clearly evident that the BMPs-embedded Ti remarkably reduces the initial burst release of Ti compared to porous Ti. This release trend can be explained on the basis of the narrow pores like an ant tunnel when pressed. These narrow pores allows for a more controlled and long-termed release. The cell viability after culturing for 3 days was not influenced very much by embedded BMP. However, the ALP activity of the cells cultured for 7 days on embedded Ti was significantly higher than that on the bare Ti for the same period of time. In vivo performances of the Ti embedded with BMPs were assessed using a cortical defect model in rabbit proximal femur.

Speaker
Biography:

Iordana Neamtu has published more than 50 papers in quotated journals and participated in more than 15 Romanian Projects.

Abstract:

Utilization of polymers as biomaterials is greatly impacted the progress of modern medicine. In order to fit functional demand, materials with desired physical, chemical, biological, biomechanical and degradation properties must be selected. Luckily, a wide range of natural and synthetic degradable polymers are investigated for biomedical applications with novel materials constantly being developed to meet new challenges. The present study is focused on the poly(anhydride maleic-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane) new copolymer synthesis by radical polymerization in dioxane, using 2,2′-azobis(2-methylpropionitrile) as free-radical initiator. The polymer matrix is subsequently modified with meso-erythritol to open maleic anhydride ring, with the aim to afford supplementary functions necessary for polymer matrix coupling with bioactive substances. Antioxidant characteristics are conferred, too. Both comonomers are able for generating special effects as for example network formation, biodegradability and biocompatibility, gel formation capacity, binding properties, amphiphilicity, good oxidative and thermal stability, good film formers, and temperature and pH sensitivity. The resulted structure is evidenced by common spectroscopic analyses, while the dual pH and temperature sensitivity is evaluated by determining the hydrodynamic radius and zeta potential. The antioxidant character is evaluated measuring the scavenger properties of the functionalized copolymer with erythritol against the 2,2-diphenyl-1-picrylhydrazyl radicals. The acute toxicity of the synthesized macromolecular compounds is estimated in vivo by mice oral administration followed by medial lethal dose determination (LD50). The obtained data include the compounds into the group of moderately toxic accordingly to Hodge and Sterner toxicity scale.

Speaker
Biography:

Mehmet Onur Aydogdu has completed his Bachelor’s degree from the Department of Biology at Marmara University. He is working at Advanced Nanomaterials Research Laboratory at Marmara University. He is interested in biology, biomaterials, design and applications of nanofiber structures for drug delivery and controlled release systems.

Abstract:

Polyurethane (PU) is one of the most popular and broadly used synthetic polymers due to its endurance, elasticity, fatigue resistance, biocompatibility and acceptance-tolerance in the body. On the other hand zeolites are aluminosilicate crystals with micro-sized porous structures. Thermally and chemically zeolites are more stable compared to the polymers. Furthermore, zeolites were reported having anti-bacterial, anti-viral effects and anti-fungal effects inside the body and on the skin. Therefore, their direct usage in biomedical application with an accompanying polymer, which includes carrier properties, may be promising. This study focuses using the electrospinning method to fabricate PU nanofibers, which enhanced by zeolite crystals. Electrospinning is a simple, effective and low cost technique, which produces both nano and micro sized scaffolds. As the results of this technique final products becomes improved with the advantages of nanotechnology. For instance, maximizing the surface to unit volume ratio is done to achieve better mechanical properties due to their very small diameter. The PU/Zeolite nanocomposite fibers were prepared in different blend ratios in order to analyze the different parameters. Each individual sample was characterized by SEM, XRD, IR and tensile measurements. Zone inhibition tests were performed in order to detect the antimicrobial activity and cell viability studies were also performed. Results indicated that PU/zeolite nanocomposite is not only more biocompatible but also has better physical properties than pure PU. Moreover, it allows the normal development and growth of cells and exhibits antimicrobial effect against bacterial strains. This nanocomposite structure is promising for their potential usage and value in biomedical engineering applications.

Speaker
Biography:

Yabin Zhu is working as professor at Medical School of Ningbo University. She was a research fellow in Biomedical engineering research centre (BMERC), Nanyang Technological University, Singapore. She has completed her B.S from Ningbo University, M.S. from Jilin University and received her Ph.D. from Zhejiang University, China. Her research interests include biomaterials, medical devices and drug delivery techniques.

Abstract:

Meshes play important roles to repair human tissue defect. In this work, human amniotic membrane (HAM) was decellularized and explored the efficacy as an implantable biological mesh. Surfactant, hypertonic saline, lipase and DNAase were used individually or collectively to remove all cell components and remain the extracellular matrix. Results of H&E and DAPI staining demonstrated that the method of surfactant and lipase combining with DNAase is the most effective treatment for HAM decellularization. Primary smooth muscle cells were seeded to evaluate the decellularized HAM’s (dHAM) in vitro cytocompatibility. The in vivo test was performed via implantation at rabbits’ uterus with clinic polypropylene mesh (PP) as the control. The results indicated that dHAM possessed good biocompatibility and will be a potential candidate for biological mesh.

Hyun-Do Jung

Korea Institute of Industrial Technology, Korea

Title: Dynamic Freeze Casting using Titanium (Ti) Powders for producing Porous Ti
Speaker
Biography:

Hyun-Do Jung has completed his PhD from Seoul National University and postdoctoral studies from Seoul National University. He is the senior researcher of Korea Institute of Industrial Technology, a premier national laboratory in Korea. He has published more than 15 papers in reputed journals and is now working on producing metal scaffold by 3D printing.

Abstract:

Freeze casting has recently received increasing interest, as it can endow porous ceramics with well-defined pore structures, such as a controlled pore size, perfect interconnections between pores. Particularly, the use of camphene as the freezing vehicle makes it possible to freeze a ceramic slurry at near room temperature, thus allowing for more flexible processing. However, camphene-based freeze casting can only be applied to ceramic powders because dispersant can be activated by electrostatic effect when using ceramic powders. So it suffers from the considerable sedimentation of relatively large metal powders during solidification, resulting in an inhomogeneous porous structure. Therefore, this study reports how porous Ti scaffolds can be produced with a uniform porous structure by freezing a Ti/camphene slurry in rotation, which is denoted as “dynamic freeze casting”. Ti/camphene slurries with Ti powder content (15vol.%) were prepared by stirring at 60 °C for 30 min. Prepared slurries were poured into cylindrical molds and frozen at 44 °C dynamically in order to avoid segregating powder from camphene. During this process, camphene crystals can nucleate and grow extensively until the slurry has solidified completely, while preserving the walls made of Ti powders, particularly due to freezing in rotation. After de-molding, the green bodies were pressed using a cold isostatic press to produce the green compact specimens. They were freeze dried to remove the frozen camphene. The 3-dimensionally interconnected large pores can be created after removing the camphene crystals. Thereafter, the samples were heated up to 1300°C, and heat treated for 2 h. The porous structures and morphology of the samples were characterized using scanning electron microscopy (SEM) and a micro–computed tomography (micro-CT). In order to evaluate their mechanical properties, their compressive stress–strain behaviors were also monitored.

Speaker
Biography:

Sandra Pietri has authored and co-authored scientific papers and completed her PhD in Pharmaceutical and Biomedical Sciences at the Université Libre de Bruxelles (ULB, Belgium) in 2010. She serves as Preclinical manager of Bone Therapeutics SA, an advanced biotechnology company with a unique approach to the development of cell therapy products for bone fracture repair and fracture prevention. She started her career at Bone Therapeutics in 2011 where she was supervisor of the in vivo preclinical department. She has acquired a broad experience in bone and cartilage scientific knowledge, in vivo disease model development and stem/ stromal cell differentiation.

Abstract:

Bone Therapeutics develops innovative osteoblastic cell therapy products for the treatment of orthopedic and spinal conditions. The company is currently evaluating its human allogeneic osteoblastic cell therapy product, ALLOB®, in spinal fusion. Although spinal fusion is routine procedure, non-union and persisting pain is still frequent irrespective of the procedure and bone graft used. The local implantation of osteoblastic cells (such as ALLOB®) in combination with bioceramics granules is expected to provide the necessary osteogenic, osteoinductive and osteoconductive properties for the enhancement of bone formation and fusion. Preclinical studies with ALLOB® have shown excellent safety and efficacy results. For example, in a mouse model of osteotomy, combining granules with ALLOB® significantly accelerates and increases the bone formation and fusion rates as compared to granules alone (fusion was observed in 40% vs. 17% at 4 weeks and in 60% vs. 0% at 8 weeks for the animals treated with ALLOB®/bioceramics and with bioceramics alone respectively). Bone Therapeutics has initiated a proof-of-concept Phase IIA open-label study to assess the safety and efficacy of ALLOB® in patients requiring spinal fusion procedures. Sixteen patients with symptomatic lumbar disc disease will be treated with a single dose of ALLOB® combined with β-TCP granules to promote bone formation and fusion of the vertebral bodies. The ALLOB®-treated patients will be evaluated over a 12-month period using both clinical and radiological parameters. To date, the first two patient cohorts have been treated without any complications or safety issues.

  • Track-1: Advanced Biomaterials
    Track-8: Biomaterials Engineering
    Track-3: Dental Biomaterials
    Track-9: Biomaterials: Synthesis and Characterization
    Track-13: Biomaterials in Biological Engineering

Session Introduction

Georgina Miranda

University of Minho, Portugal

Title: Designing Ti6Al4V doped hydroxyapatite structures for dental applications
Speaker
Biography:

Georgina Miranda earned her PhD in Mechanical Engineering from University of Minho in 2015. She has 16 papers published in ISI journals. Her PhD thesis focused on the development and characterization of aluminum composites reinforced with metals or/and ceramics. Her main research interests include metal matrix composites; interfaces; powder metallurgy; laser sintering; shape memory alloys and functionally graded materials. In January 2016 she will lead a new project on the Development of smart designed adaptive prosthesis for Orthopaedic Applications. She works as invited professor in the Mechanical Engineering Department of University of Minho and is a postdoctoral researcher in the Centre for Micro-Electro Mechanical Systems (MEMS).

Abstract:

Dental implants osteointegration is a current topic that is known to be influenced by several factors like the surgical procedure, the loading upon implantation, the implant surface and coatings and also the implant design. Ti6Al4V alloy chemical stability, mechanical properties and biocompatibility explain the great use of this alloy in dental implants. Additionally, these implants surfaces can be coated with bioactive materials like hydroxyapatite, β-TCP or bioactive glass in order to increase the cell attachment to the metal implant surface. Traditional hydroxyapatite coatings (e.g. by sol-gel dip coating) are proven to be adequate for obtaining high-quality coatings on metal substrates, however when used in dental implants, due to the implantation process, these coatings can be detached from the metal surface. In this context, a surface design that could avoid this scenario can bring advantages when regarding dental implants. Laser technology can be used for the production of a designed machined metal surface, where bioactive material can be allocated and afterwards used to sinter the hydroxyapatite powders. This work presents a new design approach for the production of Ti6Al4V doped hydroxyapatite structures for dental applications, by using laser technology.

Speaker
Biography:

Dr. Purita is director of Institute of Regenerative and Molecular Orthopedics (www.stemcellorthopedic.com) in Boca Raton, Florida. The Institute specializes in the use of Stem Cells and Platelet Rich Plasma injections. Dr. Purita is a pioneer in the use of Stem Cells and Platelet Rich Plasma. The Institute has treated some of the most prominent professional athletes from all major sports in both the U.S.A. and abroad. He received a B.S. and MD degree from Georgetown Univ. Dr. Purita is board certified in Orthopedics by ABOS. He is a Fellow American College of Surgeons, Fellow American Academy Orthopedic Surgeons, and a Fellow American Academy of Pain Management. He is also certified in Age Management Medicine. He has lectured and taught extensively throughout the world on the use of Stem Cells and Platelet Rich Plasma. He has been instrumental in helping other countries in the world establish guidelines for the use of Stem Cells in their countries. He has been invited to lecture on these techniques throughout the world as a visiting professor.

Abstract:

The presentation concerns PRP and Stem Cell (both bone marrow and adipose) injections for musculoskeletal conditions in an office setting. Indications are given as to which type of cell and technique to use to accomplish repair. Stem cells, both bone marrow derived (BMAC) and adipose, are used for the more difficult problems. PRP injections are utilized for the less severe problems. Indications are given when to use Stem Cells verses PRP and when to use both. The newest concepts in stem cell science are presented. These concepts include the clinical use of MUSE cells, exosomes, and Blastomere like stem cells. Basic science of both PRP and stem cells are discussed. This presentation defines what constitutes an effective PRP preparation. Myths concerning stem cells are dispelled. One myth is that mesenchymal stem cells are the most important stem cell. This was the initial interpretation of Dr. Arnold Caplan the father of mesenchymal stem cell science. Dr. Caplan now feels that MSCs have an immunomodulation capacity which may have a more profound and immediate effect on joint chemistry and biology. We now learn in the talk that the hematopoietic stem cells are the drivers of tissue regeneration. Also discussed are adjuncts used which enhance the results. These therapies include supplements, LED therapy, lasers, electrical stimulation, and cytokine therapy. The scientific rationale is presented for each of these entities as to how they have a direct on stem cells.

  • Track-1: Advanced Biomaterials
    Track-8: Biomaterials Engineering
    Track-3: Dental Biomaterials
    Track-9: Biomaterials: Synthesis and Characterization
    Track-13: Biomaterials in Biological Engineering
Speaker

Chair

Stella W Pang

City University of Hong Kong, Hong Kong

Session Introduction

Stella W. Pang

City University of Hong Kong, Hong Kong

Title: Promoting cell migration in confined channels with bends

Time : 15:55-16:20

Speaker
Biography:

Stella W. Pang is Chair Professor and Center Director for Biosystems, Neuroscience, and Nanotechnology at City University of Hong Kong. Previously, she was Professor and Associate Dean at University of Michigan in Ann Arbor, USA. She is a Fellow of the IEEE, ECS, and AVS.

Abstract:

Controlling cell movement and positioning are crucial for biosystems. Here we have designed channel structures to control cell migration characterisitics, which form the fundamental building block for cell positioning. A microstructured polydimethylsiloxane (PDMS) substrate was bonded to another PDMS slab by oxygen plasma, forming sealed channels with a height of 15 µm and a width of 10 μm as shown in Fig. 1(a). MC3T3-E1 osteoblast cells were seeded through an entrance port at one end of the channels, and were allowed to attach to the substrate overnight. Fig. 1(b) shows the overlapped cell migration tracks in the channels. As shown in Fig. 1(c), cells in channels with 135° bends traveled significantly further as compared to those in channels with 45° bends or in straight channels. We hypothesize that such phenomenon is cell type-specific. As we continue to build in guiding features in the channels, this will be the basis for “smart” platform or biomaterial which is capable of sorting adherent cells to predesigned locations or screening cells without applying chemical gradient or fluidic flow.

Break: Coffee Break @ Foyer Area 15:55-16:20

Horatiu Rotaru

Iuliu Hațieganu University of Medicine and Pharmacy, Romania

Title: Biocompatibility of new fiber-reinforced composite materials for craniofacial bone reconstruction

Time : 16:20-16:45

Speaker
Biography:

Horatiu Rotaru, DDS, MD, PhD is a young and proficient maxillofacial surgeon. He is head of the Department of Oral and Maxillofacial Surgery in Cluj-Napoca, Romania. He has a PhD degree since 2008. He qualified as an experienced researcher in the area of biomaterials, medical imaging, 3D engineered reconstructions. By now, he has already been a team member in 14 national and European projects, showing his particular interest in reconstructive surgery, advanced biomaterials, medical imaging and tissue engineering. He published more than 45 articles and he is also co-author in 6 books of cranio-maxillofacial surgery.

Abstract:

This study aims to assess the biocompatibility of new advanced fiber-reinforced composites (FRC) to be used for custom-made cranial implants. Four new formulations of FRC were obtained using polymeric matrices (combinations of monomers bisphenol A glycidylmethacrylate (bis-GMA), urethane dimethacrylate (UDMA), triethylene glycol dimethacrylate (TEGDMA), hydroxyethyl methacrylate (HEMA)) and E-glass fibres (300g/mp). Every FRC contains 65% E-glass and 35% polymeric matrix. Composition of polymeric matrices are: bis-GMA (21%), TEGDMA (14%) for FRC1; bis-GMA (21%), HEMA(14%) for FRC2; bis-GMA (3.5%), UDMA (21%), TEGDMA (10.5%) for FRC3 and bis-GMA (3.5%), UDMA(21%), HEMA (10.5%) for FRC4. Cytotoxicity test was performed on both human dental pulp stem cells and dermal fibroblasts. Viability was assessed by tetrazolium dye colorimetric assay. Subcutaneous implantation test was carried out on forty male Wistar rats, randomly divided into 4 groups, according to the FRC tested. Each group received subcutaneous dorsal implants. After 30 days, intensity of the inflammatory reaction, tissue repair status and presence of the capsule were the main criteria assessed. Both cell populations showed no signs of cytotoxicity following the FRC exposures. Among the FRC formulations, the best results were obtained with FRC3, followed by FRC2. FRC3 showed the mildest inflammatory reaction and this correlated both with the non-cytotoxic behavior and the presence of a well-organized fibrous capsule (Z= -3.16, p=0.002). The composite biomaterials developed may constitute an optimized alternative of the similar materials used for the reconstruction of craniofacial bone defects. According to our studies, we conclude that FRC3 is the best formulation regarding the biological behavior.

Speaker
Biography:

Mehdi Razavi is Postdoctoral Research Fellow in Biomaterials with the BCAST at Brunel University London. Prior to this appointment he joined Oklahoma State University as Research Scholar. He holds a PhD from Isfahan University of Technology in 2014. Dr. Razavi has authored over 30 peer-reviewed journal articles, 7 conference proceedings, 2 Book Chapters and 2 Books. He has been cited ~ 349 times, has an h-index: 12, and i-10 index: 13. He also serves as the author, reviewer, chief editor and member of editorial boards of numerous recognized international journals, Books and Funding agencies.

Abstract:

Development of β-type titanium (Ti) alloys with a lower elastic modulus and better ductility than common medical titanium alloys have recently attracted much attention for biomaterials applications. The aim of this in vitro research was to analyse the cellular behaviour of human embryonic kidney 293T (HEK293T) cells grown on the β-type Ti-35.5Nb-5.7Ta alloy using Alamar Blue assay to verify the cytocompatibility of this alloy. In this research, hip implants of β-type Ti-35.5Nb-5.7Ta alloy were fabricated by powder metallurgy. An advanced surface treatment technology of Laser Engineered Net Shaping (LENS) was used to apply a ZrO2/Zr coating on the implant surfaces where relative movement takes place between the implant and the bone, in order to enhance the wear resistance. The present work was conducted to evaluate the cytotoxicity of uncoated and ZrO2/Zr coated β-type Ti-35.5Nb-5.7Ta alloy in both indirect and direct contact of HEK293T cells. The cellular response was quantified by cell viability assessments using Alamar Blue assay and cell attachment. Cytotoxicity experiments did not show any toxic response of the alloys on surviving cells. HEK293T cells displayed appropriate survival rates, good cell adhesion and spreading. These results indicate good cyto-compatibility of the uncoated and ZrO2/Zr coated β-type Ti-35.5Nb-5.7Ta alloy, which allowed adhesion and proliferation of HEK293T cells to occur in both indirect and direct contact cell culture methods by Alamar Blue assay.

Speaker
Biography:

Born in Popayan, Colombia, Felipe Delgado studied medicine in the Universidad del Cauca (1984) under his father’s (Dr. José María Delgado) supervision; who was a master in human anatomy. His passion for human anatomy and biomechanics was born from his father’s influence. He makes part of the prestigious Corin Academy of UK; which has allowed his work centre (Sant Celoni) to be recognized as an excellence centre. He is also interested in aseptic loosening in THA and its relationship with THA stability. He is currently researching tribology and the design of a new prosthetic concept for hip replacement.

Abstract:

Surgical Technique: Modified Anterolateral Approach for Stable Hip (MAASH) is a novel surgical concept focused on the anatomy and biomechanics of the hip capsule. It specifically preserves all of the posterior capsule, the anterior Iliofemoral lateral ligament and the pubofemoral ligament by excising only the central third of the hip capsule (the non-innervated space or weak area) along the femoral head-neck axis. MAASH provides a novel surgical technique to all THA approaches and changes the focus from muscle balancing to capsular balancing (the box concept). This capsular approach philosophy can be used as a standard for all THAs. Objectives: Background: Dislocation, leg length limb discrepancy and aseptic loosening are major complications following total hip arthroplasty (THA). Many surgical approaches, complex surgical devices as well as computer navigation techniques have been previously described for THA. However, none of them have offered an approach that results in a wide capsular surgical working area that can assure good capsular exposure and the preservation of capsule integrity. Methods: We collected data from November 2007 to April 2015 from n= 250 patients that underwent THA using the MAASH technique. Surgical outcomes, statistical analysis, complications and conclusions of this new concept in THA approach were analyzed and reported. Results: MAASH technique offers to hip surgeons a reliable and reproducible THA approach that assures excellent leg length discrepancy results and high stability in all range of motion without impingement. Only one dislocation (0.4%) and 5 major complications (2%) were reported in the MAASH cohort, most of which occurred at the early stages of technique development. Conclusions: The MAASH technique is an anterior capsular concept for the anterolateral approach in total hip arthroplasty, which may be advantageous for active THA candidates and for patients with a high risk of dislocation as it does not rely solely on muscle balancing. The capsular balancing concept is the key factor that MAASH offers. It provides maximum stability, excellent leg length discrepancy and minimizes wear (no micro motion), which allows patients to recover fastersafer and can potentially diminish the economic burden on patients and the overall healthcare system.

  • Scientific Networking and B2B Meetings