Description

The Journal of Biomaterial Applications is at the forefront of reporting on new developments in the materials technology that supports new and improved biomaterials and medical devices. Peer-reviewed articles by biomedical specialists from around the world cover: New developments in biomaterials R&D, properties and performance, evaluation and applications; Applications in biomedical materials and devices - from sutures and wound dressings to biosensors and cardiovascular devices; Current findings in biological compatibility/incompatibility of biomaterials. The Journal of Biomaterials Applications publishes original articles that emphasize the development, manufacture and clinical applications of biomaterials. Biomaterials continue to be one of the most rapidly growing areas of research in plastics today and certainly one of the biggest technical challenges, since biomaterial performance is dependent on polymer compatibility with the aggressive biological environment. The Journal cuts across disciplines and focuses on medical research and topics that present the broadest view of practical applications of biomaterials in actual clinical use.

Publisher details

SAGE Publications

Publications in this journal

• Synthesis and biocompatibility properties of polyester containing various diacid based on isosorbide.

  Authors: Hyung-Seok Park, Myoung-Seon Gong, Jonathan C Knowles

  Journal of biomaterials applications.

  Biocompatibility polyesters were prepared from isosorbide, various aliphatic diacid via a simple non-solvent polycondensation with a low toxicity catalyst. The successful synthesis of the polyestersBiocompatibility polyesters were prepared from isosorbide, various aliphatic diacid via a simple non-solvent polycondensation with a low toxicity catalyst. The successful synthesis of the polyesters was confirmed by gel permeation chromatography, (1)H-nuclear magnetic resonance and Fourier transform infrared spectroscopes, and differential scanning calorimetry. The degradation tests were performed at 37°C in phosphate buffer solution (approximately pH 7.3). The in vitro cytocompatibility test results following culture of osteoblasts on the polymer surface showed that relative cell number on poly(isosorbide sebacate) and poly(isosorbide adipate) films after 5 days of culture on polymer films proliferated at least as well as those on a culture plate.

• Preparation and in vitro characterization of dexamethasone-loaded poly(D,L-lactic acid) microspheres embedded in poly(ethylene glycol)-poly({varepsilon}-caprolactone)-poly(ethylene glycol) hydrogel for orthopedic tissue engineering.

  Authors: Min Fan, Qingfa Guo, Jingcong Luo, Feng Luo, Ping Xie, Xiaohai Tang, Zhiyong Qian

  Journal of biomaterials applications.

  The corium is decreased to about half of its thickness in skin defects and wrinkles due to gravity and environment. In this study, dexamethasone/poly(D,L-lactic acid) (Mn = 160,000) microspheres wereThe corium is decreased to about half of its thickness in skin defects and wrinkles due to gravity and environment. In this study, dexamethasone/poly(D,L-lactic acid) (Mn = 160,000) microspheres were incorporated into poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (Mn = 3300) hydrogel to prepare an injectable hydrogel composite. The composite was designed to increase the thickness of the corium. Dexamethasone/poly(D,L-lactic acid) microspheres were prepared by oil-in-water emulsion/solvent evaporation technique. The properties of microspheres were investigated by size distribution measurement, scanning electron microscope and x-ray diffraction. Drug loading, encapsulation efficiency, and drug delivery behavior of microspheres were also studied in detail. Cell adhesion of microspheres was investigated by NIH3T3 cell in vitro. The properties of hydrogel composite were investigated by scanning electron microscope, rheological measurements and methyl thiazolyl tetrazolium assay. Drug release from composite was determined by HPLC-UV analysis. These results suggested that poly(D,L-lactic acid) microspheres encapsulating dexamethasone embedded in poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) hydrogel might have prospective application in orthopedic tissue engineering field.

• Polyelectrolyte based molecular carriers : The role of self-assembled proteins in permeability properties.

  Authors: Neda Habibi, Laura Pastorino, Oscar Herrera Sandoval, Carmelina Ruggiero

  Journal of biomaterials applications.

  Polyelectrolyte capsules are seen as promising nanotechnology based drug delivery systems. In previous works, we have demonstrated the possibility to fabricate bio-activated surface layer containingPolyelectrolyte capsules are seen as promising nanotechnology based drug delivery systems. In previous works, we have demonstrated the possibility to fabricate bio-activated surface layer containing capsules with improved features in terms of biocompatibility. In this study, we have characterized the permeability properties of such capsules towards low and high molecular weight molecules, including proteins. The results indicated that the presence of the surface layer strongly affects the permeability properties of the capsules in terms of loading capacity which was found to be higher compared to that of plain capsules. These properties make such systems interesting candidates as drug delivery platforms.

• Nanoformulation of paclitaxel to enhance cancer therapy.

  Authors: Quanrong Gu, James Z Xing, Min Huang, Xiaojing Zhang, Jie Chen

  Journal of biomaterials applications.

  Paclitaxel is a microtubule inhibitor causing mitotic arrest and is widely used in cancer chemotherapy. However, its poor water solubility restricts its direct clinical applications. In this article,Paclitaxel is a microtubule inhibitor causing mitotic arrest and is widely used in cancer chemotherapy. However, its poor water solubility restricts its direct clinical applications. In this article, we report paclitaxel-loaded nanoparticles that are water soluble and that can improve the drug's bio-distribution and therapeutic efficacy. Paclitaxel-loaded nanoparticles were synthesized by using Pluronic copolymers (F-68 and P-123) and surfactant (Span 40) as nanocarrier. The toxicity and cellular uptake of paclitaxel-loaded nanoparticles were evaluated. The paclitaxel-loaded nanoparticles can completely disperse into phosphate buffer saline to produce a clear aqueous suspension. Based on HPLC analysis, the drug-loading rate is 9.0 ± 0.1% while drug encapsulation efficiency is 99.0 ± 1.0%. The cytotoxicity assay was performed using breast cancer MCF-7 and cervical cancer Hela cells. For MCF-7 cells, the half maximal inhibitory concentrations (IC(50)) of paclitaxel-loaded nanoparticles and paclitaxel are 8.5 ± 0.3 and 14.0 ± 0.7 ng/mL at 48 hours and 3.5 ± 0.4 and 5.2 ± 0.5 ng/mL at 72 hours across several runs. IC(50) of paclitaxel-loaded nanoparticles and paclitaxel for Hela cells are 5.0 ± 0.3 and 8.0 ± 0.3 ng/mL at 48 hours and 2.0 ± 0.1 and 6.5 ± 0.3 ng/mL at 72 hours. In-vitro studies show that the drug's nanoformulation gives obvious enhancements in the drug's efficiency at killing cancer cells over paclitaxel alone. Materials of the nanocarrier used for nanoformulation are approved with low toxicity according to the result of cell studies. Conclusion: paclitaxel-loaded nanoparticles greatly improved the physicochemical properties of paclitaxel without modifying its chemical structure, allowing for deep-site cancer drug delivery and enhancing the drug therapeutic efficiency.

• The effects of hyaluronic acid incorporated as a wetting agent on lysozyme denaturation in model contact lens materials.

  Authors: Andrea Weeks, Adrienne Boone, Doerte Luensmann, Lyndon Jones, Heather Sheardown

  Journal of biomaterials applications.

  Conventional and silicone hydrogels as models for contact lenses were prepared to determine the effect of the presence of hyaluronic acid on lysozyme sorption and denaturation. Hyaluronic acid wasConventional and silicone hydrogels as models for contact lenses were prepared to determine the effect of the presence of hyaluronic acid on lysozyme sorption and denaturation. Hyaluronic acid was loaded into poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) hydrogels, which served as models for conventional and silicone hydrogel contact lens materials. The hyaluronic acid was cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide in the presence of dendrimers. Active lysozyme was quantified using a Micrococcus lysodeikticus assay while total lysozyme was determined using 125-I radiolabeled protein. To examine the location of hyaluronic acid in the gels, 6-aminofluorescein labeled hyaluronic acid was incorporated into the gels using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry and the gels were examined using confocal laser scanning microscopy. Hyaluronic acid incorporation significantly reduced lysozyme sorption in poly(2-hydroxyethyl methacrylate) (p < 0.00001) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) (p < 0.001) hydrogels, with the modified materials sorbing only 20% and 16% that of the control, respectively. More importantly, hyaluronic acid also decreased lysozyme denaturation in poly(2-hydroxyethyl methacrylate) (p < 0.005) and poly(2-hydroxyethyl methacrylate)/TRIS - methacryloxypropyltris (trimethylsiloxy silane) (p < 0.02) hydrogels. The confocal laser scanning microscopy results showed that the hyaluronic acid distribution was dependent on both the material type and the molecular weight of hyaluronic acid. This study demonstrates that hyaluronic acid incorporated as a wetting agent has the potential to reduce lysozyme sorption and denaturation in contact lens applications. The distribution of hyaluronic acid within hydrogels appears to affect denaturation, with more surface mobile, lower molecular weight hyaluronic acid being more effective in preventing denaturation.

• Synthesis and characterization of ZnS: Mn/ZnS core/shell nanoparticles for tumor targeting and imaging in vivo.

  Authors: Zhangsen Yu, Xiying Ma, Bin Yu, Yuefang Pan, Zhaogang Liu

  Journal of biomaterials applications.

  Fluorescence imaging technique has been used for imaging of biological cells and tissues in vivo. The Cd-free luminescent quantum dots conjugating with a cancer targeting ligand has been taken as aFluorescence imaging technique has been used for imaging of biological cells and tissues in vivo. The Cd-free luminescent quantum dots conjugating with a cancer targeting ligand has been taken as a promising biocompatibility and low cytotoxicity system for targeted cancer imaging. This work reports the synthesis of fluorescent-doped core/shell quantum dots of water-soluble manganese-doped zinc sulfide. Quantum dots of manganese-doped zinc sulfide were prepared by nucleation doping strategy, with 3-mercaptopropionic acid as stabilizer at 90°C in aqueous solution. The manganese-doped zinc sulfide nanoparticles exhibit strong orange fluorescence under UV irradiation, resistance to photo-bleaching, and low-cytotoxicity to HeLa cells. The structure and optical properties of nanoparticles were characterized by scanning electron microscope, X-ray diffraction, dynamic light scattering, and photoluminescence emission spectroscopy. Manganese-doped zinc sulfide nanoparticles conjugated with folic acid using 2,2'-(ethylenedioxy)-bis-(ethylamine) as the linker. The covalent binding of both 2,2'-(ethylenedioxy)-bis-(ethylamine) and folic acid on the surface of manganese-doped zinc sulfide nanoparticles probed by Fourier transform infrared spectroscopy detection. Furthermore, in vitro cytotoxicity assessment of manganese-doped zinc sulfide-folic acid probes use HeLa cells. The obtained fluorescent probes (manganese-doped zinc sulfide) were used for tumor targeting and imaging in vivo. The manganese-doped zinc sulfide-folic acid fluorescent probes which targeting the tumor cells in the body of nude mouse tumor model would emit orange fluorescence, when exposed to a 365 nm lamp. We investigate the biodistribution of the manganese-doped zinc sulfide-folic acid fluorescent probes in tumor mouse model by measuring zinc concentration in tissues. These studies demonstrate the practicality of manganese-doped zinc sulfide-folic acid fluorescent probes as promising platform for tumor targeting and imaging in vivo.

• Technique for internal channelling of hydroentangled nonwoven scaffoldsto enhance cell penetration.

  Authors: Elaine R Durham, Eileen Ingham, Stephen J Russell

  Journal of biomaterials applications.

  An important requirement in thick, high-porosity scaffolds is to maximise cellular penetration into the interior and avoid necrosis during culture in vitro. Hitherto, reproducible control of the poreAn important requirement in thick, high-porosity scaffolds is to maximise cellular penetration into the interior and avoid necrosis during culture in vitro. Hitherto, reproducible control of the pore structure in nonwoven scaffolds has proved challenging. A new, channelled scaffold manufacturing process is reported based on water jet entanglement of fibres (hydroentangling) around filamentous template to form a coherent scaffold that is subsequently removed. Longitudinally-oriented channels were introduced within the scaffold in controlled proximity using 220 µm diameter cylindrical templates. In this case study, channelled scaffolds composed of poly(l-lactic acid) were manufactured and evaluated in vitro. Environmental scanning electron microscope and µCT (X-ray microtomography) confirmed channel openings in the scaffold cross-section before and after cell culture with human dermal fibroblasts up to 14 weeks. Histology at week 11 indicated that the channels promoted cell penetration and distribution within the scaffold interior. At week 14, cellular matrix deposition was evident in the internal channel walls and the entrances remained unoccluded by cellular matrix suggesting that diffusion conduits for mass transfer of nutrient to the scaffold interior could be maintained.

• Modifying three-dimensional scaffolds from novel nanocomposite materials using dissolvable porogen particles for use in liver tissue engineering.

  Authors: Hussamuddin Adwan, Barry Fuller, Clare Seldon, Brian Davidson, Alexander Seifalian

  Journal of biomaterials applications.

  Background: Although hepatocytes have a remarkable regenerative power, the rapidity of acute liver failure makes liver transplantation the only definitive treatment. Attempts to incorporateBackground: Although hepatocytes have a remarkable regenerative power, the rapidity of acute liver failure makes liver transplantation the only definitive treatment. Attempts to incorporate engineered three-dimensional liver tissue in bioartificial liver devices or in implantable tissue constructs, to treat or bridge patients to self-recovery, were met with many challenges, amongst which is to find suitable polymeric matrices. We studied the feasibility of utilising nanocomposite polymers in three-dimensional scaffolds for hepatocytes.Materials and methods: Hepatocytes (HepG2) were seeded on a flat sheet and in three-dimensional scaffolds made of a nanocomposite polymer (Polyhedral Oligomeric Silsesquioxane [POSS]-modified polycaprolactone urea urethane) alone as well as with porogen particles, i.e. glucose, sodium bicarbonate and sodium chloride. The scaffold architecture, cell attachment and morphology were studied with scanning electron microscopy, and we assessed cell viability and functionality.Results: Cell attachment to the scaffolds was demonstrated. The scaffold made with glucose particles as porogen showed a narrower range of pore size with higher porosity and better inter-pore communications and seemed to encourage near normal cell morphology. There was a steady increase of albumin secretion throughout the experiment while the control (monolayer cell culture) showed a steep decrease after day 7. At the end of the experiment, there was no significant difference in viability and functionality between the scaffolds and the control.Conclusion: In this initial study, porogen particles were used to modify the scaffolds produced from the novel polymer. Although there was no significance against the control in functionality and viability, the demonstrable attachment on scanning electron microscopy suggest potential roles for this polymer and in particular for scaffolds made with glucose particles in liver tissue engineering.

• Phase stability and rapid consolidation of hydroxyapatite-zirconia nano-coprecipitates made using continuous hydrothermal flow synthesis.

  Authors: Aqif A Chaudhry, Haixue Yan, Giuseppe Viola, Mike J Reece, Jonathan C Knowles, Kenan Gong, Ihtesham Rehman, Jawwad A Darr

  Journal of biomaterials applications.

  A rapid and continuous hydrothermal route for the synthesis of nano-sized hydroxyapatite rods co-precipitated with calcium-doped zirconia nanoparticles using a superheated water flow at 450°C andA rapid and continuous hydrothermal route for the synthesis of nano-sized hydroxyapatite rods co-precipitated with calcium-doped zirconia nanoparticles using a superheated water flow at 450°C and 24.1 MPa as a crystallizing medium is described. Hydroxyapatite and calcium-doped zirconia phases in the powder mixtures could be clearly identified based on particle size and morphology under transmission electron microscopy. Retention of a nanostructure after sintering is crucial to load-bearing applications of hydroxyapatite-based ceramics. Therefore, rapid consolidation of the co-precipitates was investigated using a spark plasma sintering furnace under a range of processing conditions. Samples nominally containing 5 and 10 wt% calcium-doped zirconia and hydroxyapatite made with Ca:P solution molar ratio 2.5 showed excellent thermal stability (investigated using in situ variable temperature X-ray diffraction) and were sintered via spark plasma sintering to >96% sintered densities at 1000°C resulting in hydroxyapatite and calcium-doped zirconia as the only two phases. Mechanical tests of spark plasma sintering sintered samples (containing 10 wt% calcium-doped zirconia) revealed a three-pt flexural strength of 107.7 MPa and Weibull modulus of 9.9. The complementary nature of the spark plasma sintering technique and continuous hydrothermal flow synthesis (which results in retention of a nanostructure even after sintering at elevated temperatures) was hence showcased.

• Hydroxyapatite nanorods: Soft-template synthesis, characterization and preliminary in vitro tests.

  Authors: Nga Kim Nguyen, Matteo Leoni, Devid Maniglio, Claudio Migliaresi

  Journal of biomaterials applications.

  Synthetic hydroxyapatite nanorods are excellent candidates for bone tissue engineering applications. In this study, hydroxyapatite nanorods resembling bone minerals were produced by usingSynthetic hydroxyapatite nanorods are excellent candidates for bone tissue engineering applications. In this study, hydroxyapatite nanorods resembling bone minerals were produced by using soft-template method with cetyltrimethylammonium bromide. Composite hydroxyapatite/poly(D, L)lactic acid films were prepared to evaluate the prepared hydroxyapatite nanorods in terms of cell affinity. Preliminary in vitro experiments showed that aspect ratio and film surface roughness play a vital role in controlling adhesion and proliferation of human osteoblast cell line MG 63. The hydroxyapatite nanorods with aspect ratios in the range of 5.94-7 were found to possess distinctive properties, with the corresponding hydroxyapatite/poly(D, L)lactic acid films promoting cellular confluence and a fast formation of collagen fibers as early as after 7 days of culture.

• Limited V-shaped cement augmentation of the proximal femur to prevent secondary hip fractures.

  Authors: Ladina Fliri, An Sermon, Dirk Wähnert, Werner Schmoelz, Michael Blauth, Markus Windolf

  Journal of biomaterials applications.

  Patients with a femoral fracture due to osteoporosis are at high risk of sustaining a secondary fracture on the contralateral side. A prophylactic mechanical reinforcement of the contralateral sidePatients with a femoral fracture due to osteoporosis are at high risk of sustaining a secondary fracture on the contralateral side. A prophylactic mechanical reinforcement of the contralateral side during operation of the initial fracture could be of interest for such patients. This biomechanical in vitro study investigates the potential of a limited V-shaped bone cement augmentation to prevent secondary hip fractures by targeting the areas of the proximal femur with the highest stresses during a fall. Five pairs of human cadaveric proximal femora were tested in a configuration simulating a fall on the greater trochanter. The femoral neck of one specimen of each pair was augmented with 8-14 ml polymethylmethacrylate from the lateral cortex towards inferior and superior, spanning a V-shaped cement pattern. Clinical relevant fractures were generated with a 45 kg mass in controlled free fall. Load-displacement data were recorded and energy to fracture, fracture load, yield load and stiffness were statistically evaluated. Augmented samples absorbed 124% more energy until fracture compared to their controls (p = 0.043). No significant differences were found between the two groups for fracture load (p = 0.5), yield load (p = 0.35) and stiffness (p = 0.5). Biomechanically, a limited V-shaped prophylactic cement augmentation carries potential to prevent secondary hip fractures indicated by increased energy absorption until fracture. Further investigations are necessary to minimize interference with the biology and to maximize the mechanical benefit of prophylactic augmentation.

• Biofunctionalisation of polymeric scaffolds for neural tissue engineering.

  Authors: T Y Wang, J S Forsythe, C L Parish, D R Nisbet

  Journal of biomaterials applications.

  Patients who experience injury to the central or peripheral nervous systems invariably suffer from a range of dysfunctions due to the limited ability for repair and reconstruction of damaged neuralPatients who experience injury to the central or peripheral nervous systems invariably suffer from a range of dysfunctions due to the limited ability for repair and reconstruction of damaged neural tissue. Whilst some treatment strategies can provide symptomatic improvement of motor and cognitive function, they fail to repair the injured circuits and rarely offer long-term disease modification. To this end, the biological molecules, used in combination with neural tissue engineering scaffolds, may provide feasible means to repair damaged neural pathways. This review will focus on three promising classes of neural tissue engineering scaffolds, namely hydrogels, electrospun nanofibres and self-assembling peptides. Additionally, the importance and methods for presenting biologically relevant molecules such as, neurotrophins, extracellular matrix proteins and protein-derived sequences that promote neuronal survival, proliferation and neurite outgrowth into the lesion will be discussed.

• Enhanced visualization of biodegradable polymeric vascular scaffolds by incorporation of gold, silver and magnetite nanoparticles.

  Authors: Frank Luderer, Ivonne Begerow, Wolfram Schmidt, Heiner Martin, Niels Grabow, Carsten M Bünger, Wolfgang Schareck, Klaus-Peter Schmitz, Katrin Sternberg

  Journal of biomaterials applications.

  Due to improved tissue regeneration and the enabling of post-operative minimally invasive interventions in the same vessel segment, biodegradable polymeric scaffolds represent a competitive approachDue to improved tissue regeneration and the enabling of post-operative minimally invasive interventions in the same vessel segment, biodegradable polymeric scaffolds represent a competitive approach to permanent metallic stents in vascular applications. Despite these advantages some challenges, such as the improvement of the scaffold mechanics and enhancement of scaffold visibility during the implantation procedure, are persisting. Therefore, the scope of our studies was to investigate the potential of gold, silver and magnetite nanoparticles incorporated in a polymeric blend of poly(L-lactide)/poly(4-hydroxybutyrate) for image enhancement in X-ray, magnetic resonance or near-infrared imaging. Their impact on mechanical properties of such modified scaffold materials was also evaluated.

• CAD-CAM-generated hydroxyapatite scaffold to replace the mandibular condyle in sheep: Preliminary results.

  Authors: Leonardo Ciocca, Davide Donati, Massimiliano Fantini, Elena Landi, Adriano Piattelli, Giovanna Iezzi, Anna Tampieri, Alessandro Spadari, Noemi Romagnoli, Roberto Scotti

  Journal of biomaterials applications.

  In this study, rapid CAD-CAM prototyping of pure hydroxyapatite to replace temporomandibular joint condyles was tested in sheep. Three adult animals were implanted with CAD-CAM-designed porousIn this study, rapid CAD-CAM prototyping of pure hydroxyapatite to replace temporomandibular joint condyles was tested in sheep. Three adult animals were implanted with CAD-CAM-designed porous hydroxyapatite scaffolds as condyle substitutes. The desired scaffold shape was achieved by subtractive automated milling machining (block reduction). Custom-made surgical guides were created by direct metal laser sintering and were used to export the virtual planning of the bone cut lines into the surgical environment. Using the same technique, fixation plates were created and applied to the scaffold pre-operatively to firmly secure the condyles to the bone and to assure primary stability of the hydroxyapatite scaffolds during masticatory function. Four months post-surgery, the sheep were sacrificed. The hydroxyapatite scaffolds were explanted, and histological specimens were prepared. Different histological tissues penetrating the scaffold macropores, the sequence of bone remodeling, new apposition of bone and/or cartilage as a consequence of the different functional anatomic role, and osseointegration at the interface between the scaffold and bone were documented. This animal model was found to be appropriate for testing CAD-CAM customization and the biomechanical properties of porous, pure hydroxyapatite scaffolds used as joint prostheses.

• Clinical assessment of calcium phosphate cement to treat tibial plateau fractures.

  Authors: Xiaofan Yin, Jianyong Li, Jun Xu, Zhongyue Huang, Ke Rong, Cunyi Fan

  Journal of biomaterials applications.

  The aim of this study was to examine histological changes in bone morphology after surgical treatment of tibial plateau fractures using calcium phosphate cement as a substitute for autologous boneThe aim of this study was to examine histological changes in bone morphology after surgical treatment of tibial plateau fractures using calcium phosphate cement as a substitute for autologous bone grafting. A total of 42 patients with tibial plateau fractures were treated with open reduction, internal fixation, and calcium phosphate cement. A further 34 control patients underwent open reduction and internal fixation. Bone samples for histology were obtained during the surgery. Bone healing and functional recovery were assessed. Bone cell counts were significantly higher in samples obtained during the second surgery (81.2) compared with the first surgery (45.4, p < 0.001). Bone healing scores significantly increased with time after surgery (p < 0.001). Mean Hospital for Special Surgery knee scores were rated "good" for both the calcium phosphate cement group (82.3) and control group (79.4) in 12 months, and were not significantly different between groups. Histological examination of samples obtained during the second surgery revealed well-arranged trabeculae, in addition to new bone and blood vessel formation. These histological, radiological, and functional findings suggest that calcium phosphate cement may be an effective substitute for autologous bone grafting to treat tibial plateau fractures.

• Effectiveness of antibacterial copper additives in silicone implants.

  Authors: Martin Gosau, Ralf Bürgers, Tobias Vollkommer, Thomas Holzmann, Lukas Prantl

  Journal of biomaterials applications.

  Staphylococcus epidermidis plays a major role in capsular contractures of silicone breast implants. This in vitro study evaluates the antibacterial effect of copper on S. epidermidis in siliconeStaphylococcus epidermidis plays a major role in capsular contractures of silicone breast implants. This in vitro study evaluates the antibacterial effect of copper on S. epidermidis in silicone implants. Specimens of a silicone material used for breast augmentation (Cu0) and specimens coated with different copper concentrations (Cu1, Cu2) were artificially aged. Surface roughness and surface free energy were assessed. The specimens were incubated in an S. epidermidis suspension. We assessed the quantification and the viability of adhering bacteria by live/dead cell labeling with fluorescence microscopy. Additionally, inhibition of bacterial growth was evaluated by agar diffusion, broth culture, and quantitative culture of surface bacteria. No significant differences in surface roughness and surface free energy were found between Cu0, Cu1 and Cu2. Aging did not change surface characteristics and the extent of bacterial adhesion. Fluorescence microscopy showed that the quantity of bacteria on Cu0 was significantly higher than that on Cu1 and Cu2. The ratio of dead to total adhering bacteria was significantly lower on Cu0 than on Cu1 and Cu2, and tended to be higher for Cu2 than for Cu1. Quantitative culture showed equal trends. Copper additives seem to have anti-adherence and bactericidal effects on S. epidermidis in vitro.

• Impact of polyelectrolytes and their corresponding multilayers to human primary endothelial cells.

  Authors: Andrea Nolte, Susanne Hossfeld, Birgit Schroeppel, Anne Mueller, Dieter Stoll, Tobias Walker, Hans Peter Wendel, Rumen Krastev

  Journal of biomaterials applications.

  The layer-by-layer technique, which allows simple preparation of polyelectrolyte multilayers, came into the focus of research for development of functionalized medical devices. Numerous literatureThe layer-by-layer technique, which allows simple preparation of polyelectrolyte multilayers, came into the focus of research for development of functionalized medical devices. Numerous literature exist that concentrate on the film build-up and the behaviour of cells on polyelectrolyte multilayers. However, in case of very soft polyelectrolyte multilayers, studies of the cell behaviour on these films are sometimes misleading with regard to clinical applications because cells do not die due to cytotoxicity but due to apoptosis by missing cell adhesion. It turns out that the adhesion in vitro, and thus, the viability of cells on polyelectrolyte multilayers is mostly influenced by their mechanical properties. In order to decide, which polyelectrolyte multilayers are suitable for implants, we take this problem into account by putting the substrates with soft films on top of pre-cultured human primary endothelial cells ('reverse assay'). Hence, the present work aims giving a more complete and reliable study of typical polyelectrolyte multilayers with regard to clinical applications.In particular, coatings consisting of hyaluronic acid and chitosan as natural polymers and sulfonated polystyrene and polyallylamine hydrochlorite as synthetic polymers were studied. The adsorption of polyelectrolytes was characterized by physico-chemical methods which show regular buildup. Biological examination of the native or modified polyelectrolyte multilayers was based on their effect to cell adhesion and morphology of endothelial cells by viability assays, immunostaining and scanning electron microscopy.Using the standard method, which is typically applied in literature - seeding cells on top of films - shows that the best adhesion and thus, viability can be achieved using sulfonated polystyrene/polyallylamine hydrochlorite. However, putting the films on top of endothelial cells reveals that hyaluronic acid/chitosan may also be suitable for clinical applications: This result is especially remarkable, since hyaluronic acid and chitosan mediate per se no cytotoxic effects, whereas the individual polyelectrolytes, sulfonated polystyrene and polyallylamine hydrochlorite, and their complexes show slight cytotoxicity.

• In vivo chondrocyte and transforming growth factor-β1 delivery using the thermosensitive chitosan/starch/β-glycerol phosphate hydrogel.

  Authors: Atchariya Faikrua, Sakchai Wittaya-Areekul, Bovornlak Oonkhanond, Jarupa Viyoch

  Journal of biomaterials applications.

  In present study, the chitosan/starch/β-glycerol phosphate hydrogel was investigated as an effective carrier for chondrocytes and delivery of transforming growth factor-β1. In vitro study indicatedIn present study, the chitosan/starch/β-glycerol phosphate hydrogel was investigated as an effective carrier for chondrocytes and delivery of transforming growth factor-β1. In vitro study indicated that transforming growth factor-β1 was released sustainably for 14 days with its biological activity to stimulate chondrocyte functions, as indicated by the strong expression of type II collagen protein. Subcutaneous implantation to rats revealed the strong expressions of type II collagen and aggrecan messenger ribonucleic acids, and also type II collagen protein was observed in the hydrogel in combination with transforming growth factor-β1 within 2 weeks. Our collective results showed the potential of chitosan/starch/β-glycerol phosphate hydrogel for effective delivery of chondrocytes and transforming growth factor-β1, and preserve chondrocytes' phenotype and functions in vitro.

• Differential cellular and microbial responses to nano-/micron-scale titanium surface roughness induced by hydrogen peroxide treatment.

  Authors: Abdulaziz E Daw, Hizbullah Aa Kazi, John S Colombo, Wendy G Rowe, David W Williams, Rachel J Waddington, David W Thomas, Ryan Moseley

  Journal of biomaterials applications.

  This study investigated the effects of combined titanium nano-/micron-scale roughness, induced by hydrogen peroxide pre-treatments, on bone marrow stromal cell responses and Porphyromonas gingivalisThis study investigated the effects of combined titanium nano-/micron-scale roughness, induced by hydrogen peroxide pre-treatments, on bone marrow stromal cell responses and Porphyromonas gingivalis adherence in vitro. Untreated surfaces exhibited nano-scale features, while hydrogen peroxide treatments promoted increased nano-/micron-scale roughness. Bone marrow stromal cell attachment and proliferation were maintained with 6 h and 24 h treatments, but significantly decreased on 1-week and 4-week-treated surfaces. Bone marrow stromal cells on 6 h-4 week-treated titanium demonstrated enhanced osteogenic differentiation versus untreated surfaces. P. gingivalis adherence was significantly increased on 24 h-4 week surfaces. Results suggest that 6 h but less than 24 h treatments maintain or promote bone marrow stromal cell responses while minimizing microbial adherence, potentially enhancing titanium surface bio-activation for osseointegration.

• Surface-functionalized diatom microcapsules for drug delivery of water-insoluble drugs.

  Authors: Moom Sinn Aw, Manpreet Bariana, Yang Yu, Jonas Addai-Mensah, Dusan Losic

  Journal of biomaterials applications.

  Naturally available and biocompatible materials are potential substitutes for synthetic mesoporous materials as suitable drug carriers for the development of cost-effective drug delivery systems.Naturally available and biocompatible materials are potential substitutes for synthetic mesoporous materials as suitable drug carriers for the development of cost-effective drug delivery systems. This work investigates the application of a porous silica material derived from diatoms, also known as diatomaceous earth. The aim is to explore the surface functionalization of diatom microcapsules and their impact on the drug loading and release characteristics of water-insoluble drugs. Indomethacin was used as the model for poorly soluble drug. The surface modification on diatoms was performed with two organosilanes; 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine and phosphonic acids (2-carboxyethyl-phosphonic acid and 16-phosphono-hexadecanoic acid) providing organic surface hydrophilic and hydrophobic properties. Extensive characterizations using scanning electron microscopy, X-ray photoelectron spectroscopy and differential scanning calorimetry was performed to confirm covalent grafting of monolayer aminosilane and phosphonic acid on the diatom surfaces. Differences in loading capacity of diatoms (15-24%) and release time (6-15 days) were observed which is due to the presence of different functional groups on the surface. It was found that 2-carboxyethyl-phosphonic acid, 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine render diatom surfaces hydrophilic, due to polar carboxyl functional group (COOH) and active amine species (NH and NH(2)) that favor drug adsorption; better encapsulation efficiency and prolonged release of drugs, over the hydrophobic surface created by 16-phosphono-hexadecanoic acid. This work demonstrates diatom porous silica as a promising drug carrier, with possibility to further improve their performances by tailoring their surface functionalities to achieve the required drug loading and release characteristics for different therapeutic conditions.

• Calcium sulfate spinal cord scaffold: a study on degradation and fibroblast growth factor 1 loading and release.

  Authors: Jonas Åberg, Olof Eriksson, Erika Spens, Jonathan Nordblom, Per Mattsson, Johan Sjödahl, Mikael Svensson, Håkan Engqvist

  Journal of biomaterials applications. 26(6):667-85.

  Currently, there is no regenerative strategy for the spinal cord that is part of clinical standard of core. Current paths usually include combinations of scaffold materials and active molecules. In aCurrently, there is no regenerative strategy for the spinal cord that is part of clinical standard of core. Current paths usually include combinations of scaffold materials and active molecules. In a recent study, a permanent dental resin scaffold for treatment of spinal cord injury was designed. The results from studies on rats were promising. However, for potential clinical use, a biodegradable scaffold material that facilitates drug delivery and the regeneration of the spinal cord needs to be developed. Also a biodegradable material is expected to allow a better evaluation of the efficacy of the surgical method. In this article, the suitability of hardened calcium sulfate cement (CSC) for use as degradable spinal cord scaffolds is investigated in bench studies and in vitro studies. Compressive strength, degradation and microstructure, and the loading capability of heparin-activated fibroblast growth factor 1 (FGF1) via soaking were evaluated. The CSC could easily be injected into the scaffold mold and the obtained scaffolds had sufficient strength to endure the loads applied during surgery. When hardened, the CSC formed a porous microstructure suitable for loading of active substances. It was shown that 10 min of FGF1 soaking was enough to obtain a sustained active FGF1 release for 20-35 days. The results showed that CSC is a promising material for spinal cord scaffold fabrication, since it is biodegradable, has sufficient strength, and allows loading and controlled release of active FGF1.

• Biosynthesis of calcium hydroxylapatite coating on sputtered Ti/TiN nano multilayers and their corrosion behavior in simulated body solution.

  Authors: Balasubramanian Subramanian, Perumal Dhandapani, Sundaram Maruthamuthu, Muthirulandi Jayachandran

  Journal of biomaterials applications. 26(6):687-705.

  Titanium/titanium nitride (Ti/TiN) nanoscale multilayered films were deposited onto 316L stainless steel substrates by reactive magnetron sputtering using a Ti target. Coatings characterized by X-rayTitanium/titanium nitride (Ti/TiN) nanoscale multilayered films were deposited onto 316L stainless steel substrates by reactive magnetron sputtering using a Ti target. Coatings characterized by X-ray diffraction showed that the stack possesses centered cubic structure. The X-ray photoelectron spectroscopy survey spectra on the etched surfaces of the stack film on steel exhibited the characteristic Ti2p, N1s, and O1s peaks at the corresponding binding energies 454.5, 397.0, and 530.6 eV, respectively. Platelet adhesion experiments were carried out to examine the interaction between blood and the materials in vitro. The results indicated that the smoothness and lower isoelectric point contribute to better hemocompatibility of the Ti/TiN nanoscale multilayered coating. The biomediated synthesis of calcium hydroxylapatite (HA) was carried out on coated substrates using calcium-depositing bacteria. The observation of low corrosion current density (I(corr)) for the calcium HA-coated Ti/TiN specimens in simulated body fluid confirmed their highly resistive nature under the testing condition.

• Bactericidal effect of silver-reinforced carbon nanotube and hydroxyapatite composites.

  Authors: Mohammad Atif Faiz Afzal, Sushma Kalmodia, Pallavi Kesarwani, Bikramjit Basu, Kantesh Balani

  Journal of biomaterials applications.

  Bacterial infection remains an important risk factor after orthopedic surgery. The present paper reports the synthesis of hydroxyapatite-silver (HA-Ag) and carbon nanotube-silver (CNT-Ag) compositesBacterial infection remains an important risk factor after orthopedic surgery. The present paper reports the synthesis of hydroxyapatite-silver (HA-Ag) and carbon nanotube-silver (CNT-Ag) composites via spark plasma sintering (SPS) route. The retention of the initial phases after SPS was confirmed by phase analysis using X-ray diffraction and Raman spectroscopy. Energy dispersive spectrum analysis showed that Ag was distributed uniformly in the CNT/HA matrix. The breakage of CNTs into spheroid particles at higher temperatures (1700°C) is attributed to the Rayleigh instability criterion. Mechanical properties (hardness and elastic modulus) of the samples were evaluated using nanoindentation testing. Ag reinforcement resulted in the enhancement of hardness (by ∼15%) and elastic modulus (∼5%) of HA samples, whereas Ag reinforcement in CNT, Ag addition does not have much effect on hardness (0.3 GPa) and elastic modulus (5 GPa). The antibacterial tests performed using Escherichia coli and Staphylococcus epidermidis showed significant decrease (by ∼65-86%) in the number of adhered bacteria in HA/CNT composites reinforced with 5% Ag nanoparticles. Thus, Ag-reinforced HA/CNT can serve as potential antibacterial biocomposites.

• Evaluation of nano-biphasic calcium phosphate ceramics for bone tissue engineering applications: In vitro and preliminary in vivo studies.

  Authors: Sujatha Reddy, Samiksha Wasnik, Avijit Guha, Jerald Mahesh Kumar, Arvind Sinha, Shashi Singh

  Journal of biomaterials applications.

  Reconstruction of critical sized bone injuries is a major problem that continues to inspire the design of new materials and grafts. Natural ceramics (hydroxyapatite (HA) coralline HA, or syntheticReconstruction of critical sized bone injuries is a major problem that continues to inspire the design of new materials and grafts. Natural ceramics (hydroxyapatite (HA) coralline HA, or synthetic HA) and β-tricalcium phosphate (β-TCP) are being explored for use as scaffolds in bone tissue engineering, among several other materials. The present study evaluated the bone forming capacity of nanosize bioceramics synthesized in situ in poly-vinyl alcohol (PVA) with different ratios of HA and β-TCP; the Ca/P ratio was 1.62 for bioceramic P1, 1.60 for P2 and 1.58 for P3. Further osteogenesis in vitro with mesenchymal stem cells (MSC) acquired from different sources for osteogenesis in vitro and their bone healing properties in vivo were also evaluated. MSC isolated from human placenta, Wharton's jelly from umbilical cord, fetal bone marrow and adipose tissue, cultured in the presence of nanosize bioceramic particles, were monitored for osteogenic differentiation. Placental cells showed the best osteogenic potential of the different MSC studied on the basis of expression of osteogenic markers. Complete regeneration of the damaged region was observed in vivo when MSC derived from placenta were used with nanoceramic (Ca/P ratio 1.58) in the experimental defect created in the femur of Wistar rats. Even small variation in the Ca/P ratio can alter the outcome of tissue constructs.

• Nanofiber scaffold gradients for interfacial tissue engineering.

  Authors: Murugan Ramalingam, Marian F Young, Vinoy Thomas, Limin Sun, Laurence C Chow, Christopher K Tison, Kaushik Chatterjee, William C Miles, Carl G Simon

  Journal of biomaterials applications.

  We have designed a 2-spinnerette device that can directly electrospin nanofiber scaffolds containing a gradient in composition that can be used to engineer interfacial tissues such as ligament andWe have designed a 2-spinnerette device that can directly electrospin nanofiber scaffolds containing a gradient in composition that can be used to engineer interfacial tissues such as ligament and tendon. Two types of nanofibers are simultaneously electrospun in an overlapping pattern to create a nonwoven mat of nanofibers containing a composition gradient. The approach is an advance over previous methods due to its versatility - gradients can be formed from any materials that can be electrospun. A dye was used to characterize the 2-spinnerette approach and applicability to tissue engineering was demonstrated by fabricating nanofibers with gradients in amorphous calcium phosphate nanoparticles (nACP). Adhesion and proliferation of osteogenic cells (MC3T3-E1 murine pre-osteoblasts) on gradients was enhanced on the regions of the gradients that contained higher nACP content yielding a graded osteoblast response. Since increases in soluble calcium and phosphate ions stimulate osteoblast function, we measured their release and observed significant release from nanofibers containing nACP. The nanofiber-nACP gradients fabricated herein can be applied to generate tissues with osteoblast gradients such as ligaments or tendons. In conclusion, these results introduce a versatile approach for fabricating nanofiber gradients that can have application for engineering graded tissues.

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