Day 2 :
- Track-10: Tissue Engineering and Regenerative Medicine
Track-7: Biomaterials and Nanotechnology
Chair
Anand Ramamurthi
Cleveland Clinic, USA
Co-Chair
Dora Alicia Cortes Hernandez
CINVESTAV-Mexico, USA
Session Introduction
Anand Ramamurthi
Cleveland Clinic, USA
Title: Cathepsin-K antibody-conjugated pro-matrix regenerative nanoparticles for abdominal aortic aneurysm repair
Time : 10:30-10:55
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.
Dora Alicia Cortés Hernández
CINESTAV-México, USA
Title: Synthesis and characterization of MnGaFe2O4 magnetic nanoparticles for their potential use in biomedical applications
Time : 10:55-11:20
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.
Donald A Wellings
SpheriTech Ltd, UK
Title: Novel bioresorbable scaffolds for 3D cell culture and tissue repair
Time : 11:45-12:10
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.
Maria Tomoaia-Cotisel
Cluj-Napoca, Romania
Title: Innovative substituted hydroxyapatites and collagen scaffolds for enhanced adhesion, growth and proliferation of human osteoblasts in vitro
Time : 12:10-12:35
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
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.
Xu Yuanhao
City University of Hong Kong,Hong Kong
Title: Dynamics of Natural Killer Cells Cytotoxicity in Microwell Arrays with Connecting Channels
Time : 12:55-13:15
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.
Luanda C Lins
Université de Lyon, France
Title: Electrospinning of PVDF aligned fibers and their potential in neural tissue engineering
Time : 14:05-14:25
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.
Shima Salmasi
University College London, UK
Title: The role of nanotopography on the design of an optimum nanohydroxyapatite/polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane nanocomposite scaffold for bone tissue engineering.
Time : 14:25-14:45
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.
Julian F Dye
University of Oxford, UK
Title: Emergent design of an hierarchically structured bio-intelligent scaffold for vasculogenesis and accelerated healing
Time : 14:45-15:10
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.
Madhu Gupta
Dr. H.S. Gour University, India
Title: Cyclic NGR peptide anchored block co-polymeric nanoparticles for site specific drug delivery for solid tumour therapy
Time : 12.00-12.25
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
Chair
Xiaohui Zhang
Lehigh University, USA
Session Introduction
Xiaohui Zhang
Lehigh University, USA
Title: Biomechanical characterization of von Willebrand factor – a giant multimeric plasma protein
Time : 15:10-15:35
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.
Marcus Caine
Biocompatibles UK Ltd, UK
Title: In vitro methods for evaluation of novel radiopaque embolic flow properties
Time : 15:35-16:00
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.
Tanya Sian Swaine
Biocompatibles UK Ltd, UK
Title: Novel method for the evaluation of drug release from drug-eluting beads
Time : 16:00-16:20
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.
Luanda Chaves Vieira Lins
National Institute of Applied Sciences, France
Title: Electrospinning of PVDF aligned fibers and their potential in neural tissue engineering
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.
Beata Chertok
University of Michigan, USA
Title: Engineering active biomaterial platforms for targeted and image-monitored drug delivery
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.
Omoruyi. G. Idemudia
University of Fort Hare, South Africa
Title: Design of new 4-benzoylpyrazolone based sulfanilamide azomethine and its Pd/Pt complexes; synthesis, characterization and therapeutic studies.
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).
Oladele Isiaka Oluwole
Federal University of Technology, Nigeria
Title: Impact of carbonized and unmodified cow bone on the mechanical properties of reinforced polyester composites for biomedical applications
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.
- 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
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.
Aurica P Chiriac
“Petru Poni†Institute of Macromolecular Chemistry, Romania
Title: Preparation of a new drug delivery carrier based on hydrogels of hyaluronic acid crosslinked with poly(itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) copolymers
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.
Giulia Neri
University of Messina, Italy
Title: Silibinin-conjugated graphene and hyaluronic acid platforms for osteosarcoma targeting
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.
Anna Constantinou
Imperial College London, UK
Title: Thermo-responsive ABC triblock terpolymers for 3-D printing
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
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.
Iordana Neamtu
Petru Poni Institute of Macromolecular Chemistry, Romania
Title: Functionalized copolymer matrix based on poly(maleic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) with potential biomedical applications
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.
Mehmet Onur Aydogdu
Marmara University, Turkey
Title: Production of the polyurethane/zeolite nanocomposites with electrospinning method for biomedical engineering applications
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.
Yabin Zhu
Ningbo University, China
Title: Biocompatible surgical meshes from de-cellularized amniotic membrane and polyurethane
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
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 castingâ€. 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.
Sandra Pietri
Bone Therapeutics, Belgium
Title: Osteogenic potential of ALLOB® combined with bioceramics in spinal fusion
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.