Annual Conference and Expo on Biomaterials March 14-16, 2016 London, UK

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.

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.

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.

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 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.

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 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.

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.

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.

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

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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. Moreover, variations in the administration style of the physician have been shown to play a significant part in the intra-tumoural distribution. 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.

Elena Kharapudtchenko has completed her Bachelor course at the age of 22 years from National Research Tomsk State University and is taking her Master course from National Research Tomsk Polytechnic University Physical Technical Institute. She is a young researcher, taking part in some projects realized by the university.

Hybrid multilayer coatings were obtained on titanium substrates by the combination of two methods: the micro-arc oxidation in phosphoric acid solution with the addition of calcium compounds to high supersaturated state and RF magnetron sputtering (13.56 MHz) of the target made of synthetic hydroxyapatite. 16 different types of coatings were formed and in vitro studies were conducted in accordance with ISO 23317. The studies of the coatings roughness, SEM, XRF of the samples before and after exposure to SBF were performed. The features of morphology, chemical and phase composition of the studied coatings were shown.