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

• Carbon Coatings for Cardiovascular Applications: Physico-Chemical Properties and Blood Compatibility.

  Authors: Mariangela Fedel, Antonella Motta, Devid Maniglio, Claudio Migliaresi

  Journal of biomaterials applications.

  Two different types of carbon coatings for cardiovascular applications were characterized both as regards to their physico-chemical properties and blood compatibility upon contact with human plasmaTwo different types of carbon coatings for cardiovascular applications were characterized both as regards to their physico-chemical properties and blood compatibility upon contact with human plasma and platelets. The samples were analyzed by means of a wide range of techniques, including scanning electron microscopy (SEM) and atomic force microscopy (AFM), contact angle goniometry, Raman spectroscopy and X-ray Diffraction (XRD). Multiple tests have been performed to evaluate plasma protein adsorption and platelets adhesion and activation, and to investigate possible correlations between the surface properties of the materials and their blood compatibility. We proposed a similar mechanism of blood/material interaction for the carbon-based materials tested. It has been suggested that the characteristic wettability and surface heterogeneity of the coatings guide protein adsorption and retention onto the carbon surfaces, promoting a preferential, extensive and tight adsorption of albumin molecules, that in turn leads to surface passivation and inhibits subsequent platelets adhesion and activation.

• Evaluation by Bone Scintigraphy of Osteogenic Activity of Commercial Bioceramics (Porous {beta}-TCP and HAp Particles) Subcutaneously Implanted in Rats.

  Authors: Hitoshi Nakayama, Tomoyuki Kawase, Hiroyuki Kogami, Kazuhiro Okuda, Hikaru Inoue, Takaaki Oda, Kazuhide Hayama, Makoto Tsuchimochi, Larry F Wolff

  Journal of biomaterials applications.

  Osteogenic potential of biomaterials used in bone regenerative therapy has been mainly examined in an animal-implantation study. We have here evaluated the applicability of bone scintigraphy inOsteogenic potential of biomaterials used in bone regenerative therapy has been mainly examined in an animal-implantation study. We have here evaluated the applicability of bone scintigraphy in imaging ectopic bone formation, especially its initial phase, by beta-tricalcium phosphate (beta-TCP) particles that were implanted in rat dorsal subcutaneous tissues. In implanted osteogenic osteosarcoma cells used as a positive control, osteoid formation was found by histological examination and bone scintigraphy using (99m)Tc- hydroxymethyl diphosphonate (HMDP) at 2 and 3 weeks post-implantation, respectively, while the microfocus-computed tomography (microCT) system required further mineralization, which occurred at 4 weeks. Implantation of beta-TCP particles alone induced only faint biomineralization inside the particles, which could be microscopically detected by calcein chelation at 2 weeks post-implantation, but not by other histological examinations (e.g., HE staining) or microCT. However, the bone scintigraphy successfully detected this microscopic change at 1 week. Implanted hydroxyapatite (HAp) particles alone used as a negative control did not induce mineralization at microscopic levels, and therefore nothing was detected by either calcein chelation or bone scintigraphy. In conclusion, the bone scintigraphic methodology, although exhibiting less quantitation and resolution, would be applicable as a non-invasive, highly sensitive methodology in detecting the initial, microscopic changes associated with mineralization.

• Biological Response of Osteosarcoma Cells to Size-Controlled Nanostructured Hydroxyapatite.

  Authors: Zhongli Shi, Xin Huang, Bing Liu, Huimin Tao, Yurong Cai, Ruikang Tang

  Journal of biomaterials applications.

  Osteosarcoma is a primary malignant bone tumor, most prevalent in children and adolescents, and is usually highly aggressive and eventually lethal. Despite multimodal therapies, there is no effectiveOsteosarcoma is a primary malignant bone tumor, most prevalent in children and adolescents, and is usually highly aggressive and eventually lethal. Despite multimodal therapies, there is no effective approach to treat this malignant disease. In this study, we observed the biological response of osteosarcoma cells to two kinds of hydroxyapatite nanoparticles (Nano HA), NanoHA-S and NanoHA-L. These nanospheres have the same crystallinity (phase) and morphology, but they differ in size. Cells treated with two kinds of Nano HA were inhibited and mainly led to apoptotic cell death. Caspase-9-dependent intrinsic apoptotic pathway plays a role. It was interesting that the suppression and the apoptosis of osteosarcoma cells was directly related to the size of nanoparticles and that the larger-sized Nano HA exhibited more effectiveness than the smaller one. This in vitro study suggested the potential of size-controlled calcium phosphate nanoparticles for use in therapeutic replacement and reconstruction of bone merits after osteosarcoma extraction.

• Montmorillonite-Alginate Nanocomposites as a Drug Delivery System: Intercalation and In Vitro Release of Vitamin B1 and Vitamin B6.

  Authors: Bhavesh D Kevadiya, Ghanshyam V Joshi, Hashmukh A Patel, Pravin G Ingole, Haresh M Mody, Hari C Bajaj

  Journal of biomaterials applications.

  Sustained intestinal delivery of thiamine hydrochloride (Vitamin B1; VB1) and pyridoxine hydrochloride (Vitamin B6; VB6) seems to be a feasible alternative to existing therapy. The vitamins (VB1/VB6)Sustained intestinal delivery of thiamine hydrochloride (Vitamin B1; VB1) and pyridoxine hydrochloride (Vitamin B6; VB6) seems to be a feasible alternative to existing therapy. The vitamins (VB1/VB6) intercalated in montmorillonite (MMT) and intercalated VB1/VB6-MMT hybrid is further used for synthesis of VB1/VB6-MMT-alginate nanocomposite beads by gelation method and in vitro release in the intestinal environment. The structure and surface morphology of the synthesized VB1/VB6-MMT hybrid, VB1/VB6-alginate and VB1/VB6-MMT-alginate nanocomposite beads were characterized by XRD, FT-IR, TGA and SEM. In vitro release experiments revealed that the VB1/VB6 releases suddenly from VB1/VB6-MMT hybrid and is pH dependent. The controlled release of VB1/VB6 from VB1/VB6-MMT-alginate nanocomposite beads was observed to be controlled as compared to their release from VB1/VB6-MMT hybrid and VB1/VB6-alginate beads.

• Role of Aluminium in Glass-ionomer Dental Cements and its Biological Effects.

  Authors: John W Nicholson, Beata Czarnecka

  Journal of biomaterials applications.

  The role of aluminum in glass-ionomers and resin-modified glass-ionomers for dentistry is reviewed. Aluminum is included in the glass component of these materials in the form of Al2O3 to conferThe role of aluminum in glass-ionomers and resin-modified glass-ionomers for dentistry is reviewed. Aluminum is included in the glass component of these materials in the form of Al2O3 to confer basicity on the glass and enable the glass to take part in the acid-base setting reactions. Results of studies of these reactions by FTIR and magic-angle spinning (MAS)-NMR spectroscopy are reported and the role of aluminum is discussed in detail. Aluminum has been shown to be present in the glasses in predominantly 4-coordination, as well as 5- and 6-coordination, and during setting a proportion of this is converted to 6-coordinate species within the matrix of the cement. Despite this, mature cements may contain detectable amounts of both 4- and 5-coordinate aluminum. Aluminum has been found to be leached from glass-ionomer cements, with greater amounts being released under acidic conditions. It may be associated with fluoride, with which it is known to complex strongly. Aluminum that enters the body via the gastro-intestinal tract is mainly excreted, and only about 1% ingested aluminum crosses the gut wall. Calculation shows that, if a glass-ionomer filling dissolved completely over 5 years, it would add only an extra 0.5% of the recommended maximum intake of aluminum to an adult patient. This leads to the conclusion that the release of aluminum from either type of glass-ionomer cement in the mouth poses a negligible health hazard.

• Phenotypic Re-expression of Near Quiescent Chondrocytes: The Effects of Type II Collagen and Growth Factors.

  Authors: Chin-Chean Wong, Li-Hsuan Chiu, Wen-Fu T Lai, Tsung-Tan Tsai, Chia-Lang Fang, Shih-Ching Chen, Yu-Hui Tsai

  Journal of biomaterials applications.

  After extensively expanding in monolayer culture, the cultured chondrocytes become quiescent. The aim of this study was to establish the hypothesis that the phenotypic function of extensivelyAfter extensively expanding in monolayer culture, the cultured chondrocytes become quiescent. The aim of this study was to establish the hypothesis that the phenotypic function of extensively expanded primary chondrocytes may be restored with extracellular matrix (ECM) compositions with or without growth factors. The restoring effects of these microenvironmental factors on the near quiescent passage 9 (P9) chondrocyte were investigated. The data showed that exogenous type I collagen and type II collagen at 1 : 1 ratio stimulate cell proliferation greatly while type II collagen alone was enough to revive most of cartilaginous functions of near quiescent P9 chondrocytes. Exogenous type II collagen by itself was more effective in restoring cell proliferation rate, elevating glycosaminoglycan (GAG) accumulation and promoting the re-expression of type II collagen mRNAs in the near quiescent chondrocytes. The supplement of P9 chondrocytes with type II collagen plus TGF-beta1 and IGF-I appeared essential for the re-expression of aggrecan and type II collagen mRNA in monolayer culture. In 3D type II collagen construct, P9 chondrocytes appeared healthy as chondrocytes and showed clear lacuna. However, in 3D type I collagen matrix, only some P9 chondrocytes exhibited lacuna. The cartilaginous microenvironments are crucial to restoring chondrocyte-phenotypic features of the quiescent or 'dedifferentiated' chondrocytes, implicating the potential of expanding a scarcity of healthy chondrocytes for cartilage repair or regeneration.

• Effect of a New Titanium Coating Material (CaTiO3-aC) Prepared by Thermal Decomposition Method on Osteoblastic Cell Response.

  Authors: Miho Inoue, Andrea P Rodriguez, Tohru Takagi, Naoki Katase, Midori Kubota, Noriyuki Nagai, Hitoshi Nagatsuka, Masahisa Inoue, Noriyuki Nagaoka, Shin Takagi, Kazuomi Suzuki

  Journal of biomaterials applications.

  Titanium and hydroxyapatite (HA) are widely used as biomaterials for dental and medical applications. HA-coated titanium implants have excellent biocompatibility and mechanical properties. However,Titanium and hydroxyapatite (HA) are widely used as biomaterials for dental and medical applications. HA-coated titanium implants have excellent biocompatibility and mechanical properties. However, the adherence of HA film formed on titanium substrate is weak because of the lack of chemical interaction between HA and titanium. A solution to this problem is to form an intermediate film on titanium substrate, which provide excellent adherence to both titanium substrate and HA. We developed a novel biomaterial called calcium titanate-amorphous carbon (CaTiO3-aC) coating prepared by modified thermal decomposition method. The purpose of this study was to evaluate the effect of CaTiO3-aC and HA coating (positive control), and Ti (negative control) on osteoblastic (MT3T3-E1) cell responses. An increased cellular proliferation was observed in CaTiO3-aC coating compared to HA coating. The maximum expressions of ALP activity, Col I and ALP mRNA were higher and achieved in shorter period of time in CaTiO3-aC coating compared to others. These results demonstrated that CaTiO3-aC promoted better cell attachment, cellular proliferation, and osteoblastic differentiation compared with HA. In conclusion, we suggested that CaTiO3-aC could be considered as an important candidate as a coating material.

• In vitro Proliferation and Osteogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells Cultured with Hardystonite (Ca2ZnSi2O7) and {beta}-TCP Ceramics.

  Authors: Hongxu Lu, Naoki Kawazoe, Tetsuya Tateishi, Guoping Chen, Xiaogang Jin, Jiang Chang

  Journal of biomaterials applications.

  The effects of hardystonite (Ca2ZnSi2O7, CSZn) and tricalcium phosphate (beta-TCP) on the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) wereThe effects of hardystonite (Ca2ZnSi2O7, CSZn) and tricalcium phosphate (beta-TCP) on the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) were compared by directly culturing MSCs on ceramic disks (contact mode) or separately culturing cells with ceramic disks (non-contact mode). In non-contact mode, the CSZn ceramic supported MSC proliferation more strongly than did the beta-TCP ceramic. However, in contact mode, the MSCs proliferated more quickly on the beta-TCP ceramic than they did on the CSZn ceramic. Alkaline phosphatase (ALP) staining and osteogenic gene expression analysis showed that the CSZn and beta-TCP ceramics had significant effects on the promotion of the osteogenic differentiation of MSCs in both non-contact and contact mode. Furthermore, in contact mode, the CSZn disk promoted the osteogenic differentiation of MSCs more strongly than did the beta-TCP disks. Even without the induction of dexamethasone and beta-glycerophosphate, CSZn stimulated the osteogenic differentiation of MSCs. These results suggest that CSZn ceramic would be a useful candidate material for bone regeneration and hard tissue engineering.

• The Biocompatibility of Sulfobetaine Engineered Poly(Ethylene Terephthalate) by Surface Entrapment Technique.

  Authors: Anand P Khandwekar, Mukesh Doble, Deepak P Patil, Yogesh S Shouche

  Journal of biomaterials applications.

  Sulfobetaine-modified poly(ethylene terephthalate) (PET) systems were created by physically entrapping the zwitterionic species on the PET surface. The presence of the sulfobetiane molecules on theseSulfobetaine-modified poly(ethylene terephthalate) (PET) systems were created by physically entrapping the zwitterionic species on the PET surface. The presence of the sulfobetiane molecules on these surfaces were verified by ATR-FTIR and SEM-EDAX analysis, while wettability of the films was investigated by water contact angle measurements. The blood compatibility of the modified films was evaluated by platelet adhesion in human platelet-rich plasma (PRP). The adhesion and inflammatory response of Mouse RAW 264.7 macrophage cells were studied. The surface induced cellular inflammatory response was determined by quantifying the expression levels of proinflammatory cytokines namely TNF-alpha and IL-1beta by measuring their mRNA profiles in the cells using real time polymerase chain reaction normalized to the housekeeping gene GAPDH. L-929 fibroblast cells were used to assess the propensity of the materials to support the fibroblast cell adhesion. A lower platelet adhesion and activation were observed on the sulfobetaine-modified PET film incubated in PRP after 2h when compared to control. The modified film reduced cellular adhesion events (p < 0.05) with respect to the base material, which could be linked to the reduced protein adsorption observed on this surface. The cellular inflammatory response was suppressed on sulfobetaine-modified substrate. Expression levels of pro-inflammmatory cytokines (TNF-alpha and IL-1beta) was found to be upregulated on bare PET, while it was significantly lower on modified PET (p < 0.001). Thus the sulfobetaine entrapment process can be applied on PET in order to achieve low biointeractions and reduced inflammatory host response for various biomedical and biotechnological applications.

• Biomechanical and Radiographic Comparison of Demineralized Bone Matrix, and a Coralline Hydroxyapatite in a Rabbit Spinal Fusion Model.

  Authors: Robert A Dodds, Amanda M York-Ely, Rasa Zhukauskas, Travis Arola, John Howell, Caroline Hartill, Ronald Cobb, Casey Fox

  Journal of biomaterials applications.

  The use of bone grafts is an essential component in spinal fusion. Autologous bone has been shown to result in long-term stable arthrodesis between spinal motion segments. However, autograft can beThe use of bone grafts is an essential component in spinal fusion. Autologous bone has been shown to result in long-term stable arthrodesis between spinal motion segments. However, autograft can be associated with significant morbidity and a limited supply. Alternatives, such as allogeneic demineralized bone matrix (DBM), are a potential source and supplement to autograft bone. The current study compares the ability of a DBM product (BioSet((R)) RT) and a coralline hydroxyapatite (Pro Osteon((R)) 500R), for inducing spinal fusion in a rabbit model. BioSet((R)) RT, alone or in combination with autograft, and Pro Osteon((R)) 500R were implanted in the posterior lateral inter-transverse process region of the rabbit spine. The spines were evaluated at 18 weeks for fusion of the L4-L5 transverse processes using a total of 33 skeletally mature male rabbits; 4 naïve animals were also included in the study. Samples were evaluated radiographically, histologically, by palpation, and through mechanical strength testing. Radiographical, histological, and palpation measurements demonstrated the ability of BioSet((R)) RT to induce new bone formation and bridging fusion comparable to autograft. This material performed well alone or in combination with autograft material. Despite significantly higher biomechanical testing results, minimal bone formation and fusion was recorded for the Pro Osteon((R)) 500R-treated group. This in vivo study demonstrates the ability of BioSet((R)) RT to induce new bone formation, and there was a clear relationship between bridging bone and mechanical strength.

• Femtosecond Laser Fabricated Spike Structures for Selective Control of Cellular Behavior.

  Authors: Sabrina Schlie, Elena Fadeeva, Jürgen Koch, Anaclet Ngezahayo, Boris N Chichkov

  Journal of biomaterials applications.

  In this study we investigate the potential of femtosecond laser generated micrometer sized spike structures as functional surfaces for selective cell controlling. The spike dimensions as well as theIn this study we investigate the potential of femtosecond laser generated micrometer sized spike structures as functional surfaces for selective cell controlling. The spike dimensions as well as the average spike to spike distance can be easily tuned by varying the process parameters. Moreover, negative replications in soft materials such as silicone elastomer can be produced. This allows tailoring of wetting properties of the spike structures and their negative replicas representing a reduced surface contact area. Furthermore, we investigated material effects on cellular behavior. By comparing human fibroblasts and SH-SY5Y neuroblastoma cells we found that the influence of the material was cell specific. The cells not only changed their morphology, but also the cell growth was affected. Whereas, neuroblastoma cells proliferated at the same rate on the spike structures as on the control surfaces, the proliferation of fibroblasts was reduced by the spike structures. These effects can result from the cell specific adhesion patterns as shown in this work. These findings show a possibility to design defined surface microstructures, which could control cellular behavior in a cell specific manner.

• Bone Cell Responses of Titanium Blasted with Bioactive Glass Particles.

  Authors: Chang-Rak Choi, Hye-Sun Yu, Chul-Hwan Kim, Jae Hoon Lee, Chung-Hun Oh, Hae-Won Kim, Hae-Hyoung Lee

  Journal of biomaterials applications.

  Surface modification of Ti-based metals is an important issue in improving the bone cell responses and bone-implant integration. Blasting Ti with granules (mostly alumina) is commonly used to prepareSurface modification of Ti-based metals is an important issue in improving the bone cell responses and bone-implant integration. Blasting Ti with granules (mostly alumina) is commonly used to prepare a clean surface and provide a level of roughness. In this study, glass granules with a bioactive composition were used as the blasting source to improve the surface bioactivity and biocompatibility of a Ti substrate. Bioactive glass particles with a composition of 70SiO2 . 25CaO . 5P2O5 were prepared using a sol-gel method. A Ti disc was blasted with glass particles using a dental blasting unit (BG-Ti). A Ti disc blasted with commercial spherical-shaped glass (G-Ti) and a disc without blasting (Ti) were also prepared for comparison. The blasted Ti contained a large number of glass particles after the blasting process. The surface roughness of the samples in ascending order was G-Ti > BG-Ti > Ti. Murine-derived preosteoblasts (MC3T3-E1) were seeded on the samples, and the cell growth, differentiation, and mineralization behaviors were observed. The osteoblastic cells attached well and spread actively over all the sample groups with extensive cytoskeletal processes. The level of cell growth on the BG-Ti showed a continual increase with culturing up to 7 days, showing good cell viability. However, there was no significant difference (ANOVA, p < 0.05) with respect to the G-Ti and Ti groups. In particular, the alkaline phosphatase (AP) activity of the cells was significantly higher on the BG-Ti than on the other groups after culturing for 14 days. Moreover, the mineralization behavior of the cells, as assessed by Alizarin S Red, was superior on the BG-Ti to that observed on the other groups after culturing for 14 and 28 days. Overall, the blasting of Ti with a bioactive glass composition is considered beneficial for producing substrates with enhanced osteogenic potential.

• Novel Scaffolds of Collagen with Bioactive Nanofiller for the Osteogenic Stimulation of Bone Marrow Stromal Cells.

  Authors: Seok-Jung Hong, Hye-Sun Yu, Kyung-Tae Noh, Sun-Ae Oh, Hae-Won Kim

  Journal of biomaterials applications.

  The properties of scaffolds and their roles in regulating functions of tissue cells are considered to be of utmost importance in the successful recovery of damaged tissues. Herein, novel scaffolds ofThe properties of scaffolds and their roles in regulating functions of tissue cells are considered to be of utmost importance in the successful recovery of damaged tissues. Herein, novel scaffolds of collagen and bioactive inorganic nanofiller were produced for bone tissue engineering. In addition, the in vitro responses of bone marrow-derived stromal cells (BMSCs) on these scaffolds were investigated. Glasses with bioactive compositions were prepared in nanofibrous form and homogenized with a collagen to produce hybridized porous scaffolds. The glass fibrous filaments with diameters of a few hundred nanometers were embedded well within the collagen network, characterizing a typical nanocomposite. The scaffolds showed the characteristics of a hydrogel with remarkable water uptake and swelling degree, which were similar to those of the pure collagen. In addition, the scaffolds induced the precipitation of bone-like minerals on the surface under a body-simulating medium, showing the sign of in vitro bone bioactivity. BMSCs adhered and spread well over the scaffold surface and migrated deep into the scaffold network. The osteogenic marker, alkaline phosphatase, was strongly expressed on the hybrid scaffolds, with the level higher than that on pure collagen. Overall, the collagen-inorganic nanofiller scaffolds are considered to find potential utility in bone tissue engineering.

• Editorial.

  Authors: Jonathan Knowles

  Journal of biomaterials applications. 24(1):5.

• Procoagulant Behavior and Platelet Microparticle Generation on Nanoporous Alumina.

  Authors: Natalia Ferraz, Jaan Hong, Marjam Karlsson Ott

  Journal of biomaterials applications.

  In the present work, we have investigated platelet microparticle (PMP) generation in whole blood after contact with nanoporous alumina. Alumina membranes with pore sizes of 20 and 200 nm in diameterIn the present work, we have investigated platelet microparticle (PMP) generation in whole blood after contact with nanoporous alumina. Alumina membranes with pore sizes of 20 and 200 nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200 nm pore size alumina, while PMP were practically absent on the 20 nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein-platelet interactions are taking place. A clear difference in procoagulant activity between the membranes could also be seen, 20 nm alumina showed 100% higher procoagulant activity than 200 nm membrane. By combining surface evaluation and flow cytometry analyses of the fluid phase, we are able to conclude that 200 nm pore size alumina promotes PMP generation and adhesion while the 20 nm membrane does not appreciably cause any release or adhesion of PMP, thus indicating a direct connection between PMP generation and nanoporosity.

• Histological and Radiographic Evaluations of Demineralized Bone Matrix and Coralline Hydroxyapatite in the Rabbit Tibia.

  Authors: Rasa Zhukauskas, Robert A Dodds, Caroline Hartill, Travis Arola, Ronald R Cobb, Casey Fox

  Journal of biomaterials applications.

  Complex fractures resulting in bone loss or impaired fracture healing remain problematic in trauma and orthopedic surgeries. Many bone graft substitutes have been developed and are commerciallyComplex fractures resulting in bone loss or impaired fracture healing remain problematic in trauma and orthopedic surgeries. Many bone graft substitutes have been developed and are commercially available. These products differ in their osteoconductive and osteoinductive properties. Differential enhancement of these properties may optimize the performance of these products for various orthopedic and craniofacial applications. The use of bone graft substitutes offers the ability to lessen the possible morbidity of the harvest site in autografts. The objective of the present study was to compare the ability of two bone graft substitutes, BioSet((R)) RT, an allograft demineralized bone matrix formulation, and ProOsteon((R)) 500R, a coralline hydroxyapatite, in a rabbit critical tibial defect model. BioSet((R)) RT and ProOsteon((R)) 500R were implanted into a unicortical proximal metaphyseal tibial defect and evaluated for new bone formation. Samples were analyzed radiographically and histologically at 1 day, 6 weeks, 12 weeks, and 24 weeks post surgery. Both materials were biocompatible and demonstrated significant bone growth and remodeling. At 12 weeks, the BioSet((R)) RT implanted sites demonstrated significantly more defect closure and bone remodeling as determined by radiographic analyses with 10 out of 14 defects being completely healed versus 1 out of 14 being completely healed in the ProOsteon((R)) 500R implanted sites. At 24 weeks, both materials demonstrated complete closure of the defect as determined histologically. There were no statistical differences in radiographic scores between the two implanted materials. However, there was an observable trend that the BioSet((R)) RT material generated higher histological and radiographic scores, although not statistically significant. This study provides evidence that both BioSet((R)) RT and ProOsteon((R)) 500R are biocompatible and able to induce new bone formation as measured in this rabbit model. In addition, this in vivo study demonstrates the ability of BioSet((R)) RT to induce new bone formation in a shorter timeframe than ProOsteon((R))500R.

• Feasibility and Tailoring of Bioactive Glass-ceramic Scaffolds with Gradient of Porosity for Bone Grafting.

  Authors: Chiara Vitale-Brovarone, Francesco Baino, Enrica Verné

  Journal of biomaterials applications.

  The aim of this research study is the preparation and characterization of graded glass-ceramic scaffolds that are able to mimic the structure of the natural bone tissue, formed by cortical andThe aim of this research study is the preparation and characterization of graded glass-ceramic scaffolds that are able to mimic the structure of the natural bone tissue, formed by cortical and cancellous bone. The material chosen for the scaffolds preparation is a glass belonging to the system SiO2-P2O5-CaO-MgO-Na2O-K2O (CEL2). The glass was synthesized by a conventional melting-quenching route, ground, and sieved to obtain powders of specific size. The scaffolds were fabricated using different methods: polyethylene burn-off, sponge replication, a glazing-like technique, and combinations of these methods. The scaffolds were characterized through morphological observations, density measurements, volumetric shrinkage, mechanical tests, and in vitro bioactivity tests. The features of the scaffolds prepared using the different methods were compared in terms of morphological structure, pores content, and mechanical strength. The proposed scaffolds effectively mimic the cancellous/cortical bone system in terms of structure, porosity, and mechanical strength, and they exhibit a highly bioactive behavior. Therefore, these graded grafts have a great potential for biomedical applications and can be successfully proposed for the substitution of load-bearing bone portions.

• Biocompatibility Evaluation of Chitosan-based Injectable Hydrogels for the Culturing Mice Mesenchymal Stem Cells in vitro.

  Authors: Jihong Yan, Liu Yang, Guirong Wang, Yang Xiao, Baohong Zhang, Nianmin Qi

  Journal of biomaterials applications.

  A thermosensitive polymer can be held liquid before being injected to deliver living cells or therapeutic agents and formed monolithic gels when injected in vivo. In this study, chitosan-basedA thermosensitive polymer can be held liquid before being injected to deliver living cells or therapeutic agents and formed monolithic gels when injected in vivo. In this study, chitosan-based thermosensitive hydrogels were prepared, characterized and the biocompatibility for culturing mice bone mesenchymal stem cells (BMSC) on 2D films and within 3D hydrogel were investigated. The gelation temperature and biocompatibility could be modulated by addition hydroxyethyl cellulose (HEC) to chitosan-glycerophosphate (CH-GP) formulation. The CH-GP-HEC liquid solution can turn into gel at body temperature and has highly compatible with BMSC. Therefore, the CH-GP-HEC gel could be used as an attractive injected in-situ forming scaffold for future applications of delivering biologically active therapeutics for tissue engineering filed.

• Viscoelastic Behaviors of Ultrahigh Molecular Weight Polyethylene under Three-Point Bending and Indentation Loading.

  Authors: Meng Deng, Kathryn M Uhrich

  Journal of biomaterials applications.

  Dynamic mechanical properties under three-point bending and deformation behavior under indentation loading of an ultrahigh molecular weight polyethylene (UHMWPE) were investigated in this study.Dynamic mechanical properties under three-point bending and deformation behavior under indentation loading of an ultrahigh molecular weight polyethylene (UHMWPE) were investigated in this study. Dependence of its viscoelastic properties on temperature, frequency, load level, specimen geometry and heating rates were examined. The results showed that temperature and frequency had significant effects on the response of UHMWPE to the dynamic load. With the increase in temperature, the storage modulus (E') was decreased and the loss angle (tan delta) was increased, indicating an increase in the trend in viscoelastic response of the polymer at high temperature. On the other hand, when frequency was increased, higher E' and lower tan delta were observed, suggesting that the material behaved more elastically. While the two heating rates of 5 degrees C/min and 10 degrees C/min had little effect on E' and tan delta, the load level significantly influenced the dynamic mechanical properties of the polymer. UHMWPE showed quite different responses at 0.5 and 20 Hz than at 1-10 Hz, which is worth further investigation. The results from indentation experiment showed that temperature, specimen geometry and load level had significant effects on the response of UHMWPE to the indentation load. With the increase in temperature, the penetration depth was increased, indicating an increase in the deformation trend in the polymer at high temperature. High load led to high penetration. The time-temperature superposition (TTS) method could be used to predict the long-term penetration behaviors of the polymer. From TTS analysis, the activation energy associated with penetration deformation was obtained. Further analysis showed that it might be possible to increase the resistance of UHMEPE to indentation deformation by increasing the thickness and/or decreasing the diameter of the polymer samples.

• Preparation and Evaluation of Nimesulide-loaded Ethylcellulose and Methylcellulose Nanoparticles and Microparticles for Oral Delivery.

  Authors: B Madhusudhan, N R Ravikumara, T S Nagaraj, N P Aditya, Shobarani Hiremat, Gargi Raina

  Journal of biomaterials applications.

  The present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were preparedThe present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD), polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC nanoparticles prepared by desolvation method produced discrete particles and they were characterized by SEM, AFM, and FTIR studies. The particles mean size diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC nanoparticles, respectively. Studies on drug: polymer ratio showed a linear relationship between drug concentration and percentage of loading in nanoparticles. The encapsulation efficiency decreased with the increase of nimesulide concentration with respect to polymer concentration. Encapsulation efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The in vitro release of drug-loaded nanoparticles was found to be a first order. This was significantly increased in EC nanoparticles (95.50%) in comparison with MC nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis tests of nanoparticles were carried out to ascertain the hemocompatibility and shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC formulations with nimesulide was found to be promising with slow and sustained drug release.

• Development of self-assembled nanoceramic carrier construct(s) for vaccine delivery.

  Authors: S P Vyas, Amit K Goyal, Kapil Khatri, Neeraj Mishra, Abhinav Mehta, Bhuvaneshwar Vaidya, Shailja Tiwari, Rishi Paliwal, Shivani Paliwal

  Journal of biomaterials applications.

  Hydroxyapatite (HA) has been extensively investigated as scaffolds for tissue engineering, as drug delivery agents, as non-viral gene carriers, as prosthetic coatings, and composites. Recent studiesHydroxyapatite (HA) has been extensively investigated as scaffolds for tissue engineering, as drug delivery agents, as non-viral gene carriers, as prosthetic coatings, and composites. Recent studies in our laboratory demonstrated the immunoadjuvant properties of HA when administered with malarial merozoite surface protein-119 (MSP-119). HA nanoceramic carrier was prepared by co-precipitation method that comprises of sintering and spraydrying technique. Prepared systems were characterized for crystallinity, size, shape, and antigen loading efficiency. Small size and large surface area of prepared HA demonstrated good adsorption efficiency of immunogens. Prepared nanoceramic formulations also showed slower in vitro antigen release and slower biodegrability behavior, which may lead to a prolonged exposure to antigen-presenting cells and lymphocytes. Furthermore, addition of mannose in nanoceramic formulation may additionally lead to increased stability and immunological reactions. Immunization with MSP-119 in nanoceramic-based adjuvant systems induced a vigorous immunoglobulin G (IgG) response, with higher IgG2a than IgG1 titers. In addition considerable amount of IFN-gamma and IL-2 was observed in spleen cells of mice immunized with nanoceramic-based vaccines. On the contrary, mice immunized with MSP-119 alone or with alum did not exhibit a significant cytotoxic response. The antibody responses to vaccine co-administered with HA was a mixed Th1/Th2 compared to the Th2-biased response obtained with alum. The prepared HA nanoparticles exhibit physicochemical properties that appear promising to make them a suitable immunoadjuvantto be used as antigen carriers for immunopotentiation.

• Development of Nano-hydroxyapatite/Polycarbonate Composite for Bone Repair.

  Authors: Yubao Li, Jianguo Liao, Li Zhang, Yi Zuo, Huanan Wang, Jidong Li, Qin Zou

  Journal of biomaterials applications.

  In this study, nano-hydroxyapatite (n-HA) combined polycarbonate was synthesized by a novel method. The physical and chemical property of the composite was tested. The results indicated the n-HA aIn this study, nano-hydroxyapatite (n-HA) combined polycarbonate was synthesized by a novel method. The physical and chemical property of the composite was tested. The results indicated the n-HA a crystal has the similar grain size, phase composition and crystal structure as. TEM photos results show the n-HA crystals were uniformly distributed in the polymer matrix. Then, the chemical bond between inorganic n-HA and polycarbonate was investigated and discussed. Proliferation of MSCs/composite cultured for up to 11 days the adhesion were tested by MTT and SEM. The in vitro test confirmed that the n-HA/PC composite was biocompatible and no negative effect on MSCs has found. The composite is proved to be osteoconductive, and can stimulate the growth of new bone. These results indicated that the composite meet the basic requirement of bone substitute material, and be potentially applied for clinic.

• Ectopic Bone Formation in Adipose-derived Stromal Cell-seeded Osteoinductive Calcium Phosphate Scaffolds.

  Authors: Jinfeng Yao, Xiaoyu Li, Chongyun Bao, Chaoliang Zhang, Zhiqing Chen, Hongsong Fan, Xingdong Zhang

  Journal of biomaterials applications.

  The phenomenon of osteoinduction by biomaterials has been proven and used in animals. However, whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improvesThe phenomenon of osteoinduction by biomaterials has been proven and used in animals. However, whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improves the performance of such osteoinductive biomaterial as a scaffold for tissue-engineered (TE) bone remains unclear. In this study, we compared ectopic bone formation by combining autologous adipose-derived stromal cells (ADSCs) with an osteoinductive and a nonosteoinductive biphasic calcium phosphate (BCP) ceramic to create a tissue engineering construct in the muscle of dogs. Two groups of BCP scaffolds (BCP1 and BCP2) were prepared. In each group, ADSCs were seeded, and the scaffolds without seeded cells served as controls. All implants were implanted in the back muscle of 10 adult dogs for 8 weeks and 12 weeks. Microcomputed tomography (Micro-CT) analysis and histomorphometry were performed to evaluate and quantify ectopic bone formation. The results indicated that the osteoinductive BCP1 performed significantly better compared to the nonosteoinductive BCP2 in cell-based TE bone formation ectopically. The ADSCs had a significantly positive effect on the ectopic bone formation. In addition, the usefulness of Micro-CT for the efficient and nondestructive analysis of mineralized bone and calcium phosphate scaffold was confirmed.

• Cytocompatibility and Effect of Increasing MgO Content in a Range of Quaternary Invert Phosphate-Based Glasses.

  Authors: Ifty Ahmed, Andrew Parsons, Ian Jones, Gavin Walker, Colin Scotchford, Chris Rudd

  Journal of biomaterials applications.

  Recently, phosphate-based glass (PBG) fibers have been used to reinforce the biodegradable polymers polycaprolactone and polylactic acid, in order to fabricate materials suitable for use asRecently, phosphate-based glass (PBG) fibers have been used to reinforce the biodegradable polymers polycaprolactone and polylactic acid, in order to fabricate materials suitable for use as resorbable bone fracture fixation devices. However, the PBG fibers investigated tended to degrade too quickly for application. Therefore, more durable PBG formulations were sought with emphasis remaining firmly placed on their biocompatibility. In this study, four invert PBG formulations (in the system P2O5-CaO-MgO-Na2O) were produced with fixed phosphate and calcium content at 40 and 25 mol%, respectively. MgO was added at 10-30 mol% in place of Na2O and the maximum divalent cation to phosphate ratio obtained was 1.375. Thermal analyses showed a linear increase in Tg with increasing MgO content. This was proposed to be due to an increase in the cross-link density of the glass network, which also improved the chemical durability of the glass. EDX analyses were also conducted to verify the final composition of the glass. XRD analyses confirmed the amorphous nature of the glasses investigated. Rapid quenching of the Mg30 glass revealed a degree of surface crystallization, which was shown to be a CaMgP2O7 phase. The degradation rates of the glasses investigated decreased with increasing MgO content. The decrease in rate seen was almost two orders of magnitude (a x50 difference was seen between glass Mg0 and Mg30). The cytocompatibility studies of the formulations investigated showed good cellular response over time for up to 14 days. Statistical analysis revealed that the formulations investigated gave a response comparable to the tissue culture plastic control. It is suggested that invert PBG provide degradation profiles and the cytocompatibility response desired to make these glasses useful for bone repair applications.

• Structured drug-eluting bioresorbable films: microstructure and release profile.

  Authors: M Zilberman, Y Shifrovitch, M Aviv, M Hershkovitz

  Journal of biomaterials applications. 23(5):385-406.

  Bioresorbable drug-eluting films can be used in many biomedical applications. Examples for such applications include biodegradable medical support devices which combine mechanical support with drugBioresorbable drug-eluting films can be used in many biomedical applications. Examples for such applications include biodegradable medical support devices which combine mechanical support with drug release and antibiotic-eluting film coatings for prevention of bacterial infections associated with orthopedic implants or during gingival healing. In the current study, bioresorbable drug-loaded polymer films are prepared by solution processing. Two film structures are studied: A polymer film with large drug crystals located on its surface (A-type) and a polymer film with small drug particles and crystals distributed within the bulk (B-type). The basic mode of drug dispersion/location in the film (A or B-type) is found to be determined mainly by the process of film formation and depends mainly on the solvent evaporation rate, whereas the drug's hydrophilicity has a minor effect on this structuring process. Most release profiles from A-type films exhibit a burst effect of approximately 30% and a second release stage that occurs at an approximately constant rate and is determined mainly by the polymer weight loss rate. An extremely high burst release is exhibited only by a very hydrophilic drug. The matrix (monolithic) nature of the B-type film enables release profiles that are determined mainly by the host polymer's degradation profile, with a very low burst effect in most of the studied systems. In addition to the drug location/ dispersion in the film, the host polymer and drug type also strongly affect the drug's release profile from the film. It has been demonstrated that appropriate selection of the process parameters and film components (polymer and drug) can yield film structures with desirable drug release behaviors. This can lead to the engineering of new bioresorbable drug-eluting film-based implants for various applications.

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