Journal of Biomaterials Applications recent issues

Review Paper: Role of Aluminum in Glass-ionomer Dental Cements and its Biological Effects

Nicholson, J. W., Czarnecka, B. — Fri, 23 Oct 2009 04:11:34 PDT

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 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.

Evaluation of Parenteral Depot Insulin Formulation using PLGA and PLA Microparticles

Naha, P. C., Kanchan, V., Panda, A. K. — Fri, 23 Oct 2009 04:11:35 PDT

PLGA and PLA microparticles entrapping insulin are prepared by solvent evaporation method and are evaluated in diabetes-induced rat for its efficacy in maintaining blood sugar level from a single intramuscular dose. In vitro release of insulin from PLGA and PLA microparticles are 75.35 ± 1.73% and 67.536 ± 2.23%, respectively in 168 h (7 days). Released insulin from polymer particles are mostly in monomeric form without aggregation. Optimal use of stabilizers during particle formulation helps in reducing protein denaturation and thus results in stabilized insulin-loaded polymer particles. Intramuscular administration of insulin-loaded PLGA (50 : 50) and PLA microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxaninduced diabetic rats result in 53.86 ± 4.2% and 39.52 ± 6.7% reduction in blood glucose level, respectively in 96 h. This effect continued up to 7 days in case of PLGA and PLA microparticles.

Enhanced Regeneration of Critical Bone Defects Using a Biodegradable Gelatin Sponge and {beta}-Tricalcium Phosphate with Bone Morphogenetic Protein-2

Fri, 23 Oct 2009 04:11:35 PDT

We examine the osteogenicity of a sponge biomaterial consisting of a biodegradable mixture of gelatin and β-tricalcium phosphate (βTCP) that bound bone morphogenetic protein 2 (BMP-2) in critical-sized bone defects in rats. Gelatin-βTCP sponges containing either phosphate buffered saline or incorporating BMP-2 are implanted into 5 mm diameter bone defects created in rat mandibles. We assess the defects biweekly for 8 weeks following implantation. There is significantly higher osteoinductive activity and significantly more Gla-osteocalcin content at bone-defect healing sites treated with gelatin-βTCP sponges incorporating BMP-2 than there is in those treated with sponges that did not contain BMP-2. Histologically, new bone that contains bone marrow and that is connected to the original bone almost entirely replaces the regenerated bone. These results show that biodegradable gelatin-βTCP incorporating BMP-2 is osteogenic enough to promote healing in large bone defects.

Effect of Cryoprotectant Incubation Time on Handling Properties of Allogeneic Tendons Prepared for Knee Ligament Reconstruction

Henson, J., Nyland, J., Chang, H. C., Caborn, D. N.M. — Fri, 23 Oct 2009 04:11:35 PDT

Soft tissue tendon allografts prepared for anterior cruciate ligament reconstruction are becoming increasingly popular; although concerns exist regarding increased long-term laxity and traumatic rupture rates. This qualitative study evaluated the tissue handling properties of human tibialis posterior tendons prepared using a patented process to improve allograft remodeling and ligamentization under differing cryoprotectant incubation times over 60-min rehydration. Tendons that had been incubated for 8 h had smaller diameters than those that were incubated for 2 h (8.5 ± 1.5 mm vs. 9.1 ± 1.3 mm, p = 0.02). Qualitative tissue handling property results indicated that the 8-h incubation had a negative affect on tissue color. Both incubation time and rehydration time influenced tensile stiffness, compressive resilience, and ease of tissue handling for allograft preparation with the 8-h group displaying poorer results. This study concludes that an 8-h cryoprotectant incubation time is detrimental to qualitative allogeniec tibialis posterior tendon properties. Both groups tended to improve with longer rehydration times, however the 8-h incubation group remained actively dehydrated as evidenced by its smaller diameter and poorer tissue handling properties. Suboptimally rehydrated tendons would be more likely to accrue damage during allograft preparation or during implantation.

Acrylic Copolymers as Candidates for Drug-Eluting Coating of Vascular Stents

Fri, 23 Oct 2009 04:11:35 PDT

The aim of the present work is the synthesis and characterization of polymer materials showing good adhesion, drug loading, and delivery properties, for potential cardiovascular application. In particular, poly(methylmethacrylate-co-acrylic acid) copolymers are prepared in different compositions by a radical polymerization and investigated as potential materials to coat metallic stents and to carry out a local drug release. Films obtained by dissolving the copolymer in an appropriate organic solvent (also loaded with an anti-restenosis drug, such as tacrolimus) are investigated: physicochemical properties, adhesiveness to metallic stent material, and kinetics of drug release in physiological environment are studied.

Evaluation of Biochemical the Two Cyanoacrylates: An Experimental Study in Rats

Lopez-Jornet, P., Camacho-Alonso, F., Gomez-Garcia, F. — Fri, 04 Sep 2009 07:14:15 PDT

The objective of this work is to study the biochemical effect in liver and kidney 2, 14, and 28 days after applying different tissue adhesives. In a prospective longitudinal study, 20 adult rats are assigned to two groups. After making incisions in the buccal mucosa, n-butyl-2-cyanoacrylate is applied to the first group and 2-octyl-cyanoacrylate (OCA) to the second. The biochemical parameters studied are: albumin (ALB), alanine aminotrasferase (ALT), amylase (AMY), total bilirubin (TBI), blood urea nitrogen (BUN), creatinine (CRE), glucose, globulin, total proteins (TP), and the ions calcium, phosphorus, sodium, and potassium. The group treated with n-butyl-2-cyanoacrylate shows no statistically significant differences with respect to the control, but OCA produces statistically significant alterations in BUN, ALT, TP, TBI, and AMY. The application of n-butyl-2-cyanoacrylate to wounds in the buccal mucosa produces no significant alterations in the hepatic and renal profile of the animals studied, while OCA produces greater changes in the biochemical profile.

Surface Characterization and Cytocompatibility of Three Chitosan/Polycation Composite Membranes for Guided Bone Regeneration

Zheng, Z., Wei, Y., Wang, G., Gong, Y., Zhang, X. — Fri, 04 Sep 2009 07:14:15 PDT

Guided bone regeneration is a promising surgical procedure for reconstructing bone defects. In this study, three chitosan/polycation composite membranes for guided bone regeneration are produced by blending chitosan with poly-L-lysine, polyethyleneimine, and poly-L-ornithine. For all composite membranes, the surface characteristics including surface topography, chemistry, and wettability are examined by atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle assay. Their cytocompatibility is also evaluated with MC3T3-E1 osteoblast-like cells at cell, protein, and gene levels through cell biology assays, western blot, and RT-PCR analysis. On chitosan/poly-L-lysine composite membrane, MC3T3-E1 cells present well-developed cytoskeletal organization and significantly higher adhesion, proliferation, and differentiation than those on chitosan and the other two composite membranes. Furthermore, MC3T3-E1 cells on chitosan/poly-L-lysine membrane exhibit increased phosphorylation levels of focal adhesion kinase and extracellular signal-regulated kinase 1/2, and achieve an enhanced mRNA expression of fibronectin, Runx 2, RhoA, integrin 5, and integrin β1. From our results, we conclude that chitosan/ poly-L-lysine composite membrane possesses improved cytocompatibility with osteoblasts when compared to chitosan and holds potential for guided bone regeneration in the near future.

Effects of Wollastonite on Proliferation and Differentiation of Human Bone Marrow-derived Stromal Cells in PHBV/Wollastonite Composite Scaffolds

Li, H., Zhai, W., Chang, J. — Fri, 04 Sep 2009 07:14:15 PDT

In this study, the effects of wollastonite on proliferation and differentiation of human bone marrow-derived stromal cells (hBMSCs) have been investigated based on a polyhydroxybutyrate-co-hydroxyvalerate (PHBV)/ wollastonite (W) composite scaffolds system. Cell morphology, proliferation, and differentiation were measured. The results showed that the incorporation of wollastonite benefited hBMSCs adhesion, proliferation, and differentiation rate. In addition, an increase of proliferation and differentiation rate was observed when the wollastonite content in the PHBV/W composite scaffolds increased from 10 to 20 wt%. Based on our previous studies on PHBV/W composite discs, the differentiation measurements in this paper further proved that the wollastonite itself can stimulate the hBMSCs to differentiate toward osteoblasts without any osteogenic medium, and the ionic products (Ca and Si) released from wollastonite might contribute to this advantage. It is also suggested that the osteogenic differentiation of the hBMSCs can be affected by adjusting the wollastonite content in the composite scaffolds.

A Nerve Cuff Electrode for Controlled Reshaping of Nerve Geometry

Caparso, A. V., Durand, D. M., Mansour, J. M. — Fri, 04 Sep 2009 07:14:15 PDT

The purpose of this study is the development of a nerve electrode that reorganizes nerve geometry slowly and controllably. The Flat Interface Nerve Electrode (FINE) can reshape the nerve into an elongated oval and provide selective stimulation. However, the rate of closure of this electrode is difficult to control. The Slowly Closing - FINE (SC-FINE) is designed with an opening height larger than the size of the nerve to accommodate initial swelling. The electrode closes slowly to reshape the nerve into the desired flat geometry. The SC-FINE is created by combining the reshaping properties of the FINE and the controllable degradation of Poly (DL lactic-co-glycolic) acid (PLGA). Bonding 50/50 or 65/35 PLGA to a stretched FINE increased the opening heights (OH) on average from 0.1 mm to 1.66 ± 0.45 and 2.05 ± 0.55 mm respectively. The addition of the PLGA films controls the time course of closure over a period of 16 ± 1 days and 14 to 16 hours for the 50/50 and 65/35 SC-FINEs respectively in vitro. An in vivo chronic experiment using 50/50 SC-FINEs implanted in 28 rats with an average OH of 1.87 ± 0.34 mm show that the reshaping periods in vivo and in vitro are similar.

Pluronic F-127 as a Cell Carrier for Bone Tissue Engineering

Fri, 04 Sep 2009 07:14:15 PDT

The objective of this study is to report the effect of Pluronic F-127 on osteoblast viability and phenotype maintenance in vitro. MG-63 cells are suspended in Pluronic F-127, and MTT assay, alkaline phosphatase activity, prostaglandin E₂ production, collagen-I, and cyclo-oxygenase-2 expression are assessed up to 6 days. Pluronic F-127 leads to a significant decrease in osteoblast viability throughout the 6-day experiment, without altering osteoblast phenotype. The addition of platelet-rich plasma to the polymer/cell construct leads to increased cell survival. When supplemented with bioactive factors, Pluronic F-127 could potentially be used as a cell carrier in bone tissue engineering.

C-Graft in Regeneration of Periodontal Tissue in Intrabony Periodontal Defect in Dog

Nakanishi, S., Ota, M., Shibukawa, Y., Yamada, S. — Wed, 02 Sep 2009 06:18:30 PDT

The aim of this study was to investigate the effect of C-Graft particles on formation of new cementum and bone in periodontal bone defects in dog. Healing and tissue change were histologically determined at 2, 4, 8, and 16 weeks. Little bone or cementum formation was observed in the control group. A statistically significant increase in bone and cementum formation was seen in the C-Graft group compared to the control group (75.4% vs. 44.9%, p<50.01, 80.4% vs. 46.7%, p<50.05, respectively). These findings suggest that C-Graft particles provide a scaffold for the regeneration of new bone and cementum.

Bioactive Composites Consisting of PEEK and Calcium Silicate Powders

Ill Yong Kim, , Sugino, A., Kikuta, K., Ohtsuki, C., Sung Baek Cho, — Wed, 02 Sep 2009 06:18:30 PDT

Bioactive bone-repairing materials with mechanical properties analogous to those of natural bone can be obtained through the combination of bioactive ceramic fillers with organic polymers. Previously, we developed novel bioactive microspheres in a binary CaO—SiO₂ system produced through a sol—gel process as filler for the fabrication of composites. In this study, we fabricate bioactive composites in which polyetheretherketone is reinforced with 0—50 vol% 30CaO · 70SiO₂ (CS) microspheres. The prepared composites reinforced with CS particles form hydroxyapatite on their surfaces in simulated body fluid. The induction periods of hydroxyapatite formation on the composites decrease with increasing amount of CS particles. The mechanical properties of the composites are evaluated by three-point bending test. The composites reinforced with 20 vol% CS particles show 123.5 MPa and 6.43 GPa in bending strength and Young’s modulus, respectively.

Surface Modification of Bioactive Glasses and Preparation of PDLLA/Bioactive Glass Composite Films

Gao, Y., Chang, J. — Wed, 02 Sep 2009 06:18:30 PDT

In order to improve the homogeneous dispersion of particles in the polymeric matrix, 45S5, mesoporous 58S, and 58S bioactive glasses were surface modified by esterification reactions with dodecyl alcohol at reflux temperature of 260°C (named as m-45S5, m-mesoporous 58S, and m-58S, respectively). The modified particles showed better hydrophobicity and longer time of suspension in organic matrix. The PDLLA/bioactive glass composite films were fabricated using surface modified bioactive glass particles through solvent casting-evaporation method. Surface morphology, mechanical property, and bioactivity were investigated. The results revealed that the inorganic particle distribution and tensile strength of the composite films with modified bioactive glass particles were significantly improved while great bioactive properties were maintained. Scanning electron microscopy (SEM) observation illustrated that the modified bioactive glass particles were homogeneously dispersed in the PDLLA matrix. The maximum tensile strengths of composite films with modified bioactive glass particles were higher than that of composite films with unmodified bioactive glass particles. The bioactivity of the composite films were evaluated by being soaked in the simulated body fluid (SBF) and the SEM observation of the films suggested that the modified composite films were still bioactive in that they could induce the formation of HAp on its surface and the distribution of HAp was even more homogeneous on the film. The results mentioned above indicated that the surface modification of bioactive glasses with dodecyl alcohol was an effective method to prepare PDLLA/bioactive glass composites with enhanced properties. By studying the comparisons of modification effects among the three types of bioactive glasses, we could get the conclusion that the size and morphology of the inorganic particles would greatly affect the modification effects and the properties of composites.

In vitro Degradation, Bioactivity, and Cytocompatibility of Calcium Silicate, Dimagnesium Silicate, and Tricalcium Phosphate Bioceramics

Ni, S., Chang, J. — Wed, 02 Sep 2009 06:18:30 PDT

CaSiO₃ (CS) ceramics have been regarded as a potential bioactive material for bone regeneration. Mg₂SiO₄ (M₂S) ceramic has been reported as a novel bioceramic with higher mechanical properties and good biocompatibility recently. β-Ca₂(PO₄)₂ (β-TCP) ceramic is a well-known bioactive and degradable material for bone repair. The aim of this study is to investigate and compare the effect of three bioceramics with different chemical composition on the in vitro degradation, apatite-forming ability in simulated body fluid (SBF) and cytocompatibility. The degradation was evaluated through the activation energy of Si or P ion released from ceramics and the weight loss of the ceramics in TrisHCl buffer solution. Formation of bone-like apatite on different bioceramic surfaces was investigated in SBF. The presence of bone-like apatite layer on the material surface after soaking in SBF was demonstrated by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM). The effect of ionic products from the three kinds of material dissolution on osteoblast-like cell proliferation was investigated. The results showed that the degradation rate of CS was much faster than that of β-TCP and M₂S ceramics. Apatite formation occurred on the CS ceramics quickly. However, it was less likely to occur on the surfaces of β-TCP and M₂S ceramics. The ionic products from extracts of CS and M₂S could stimulate osteoblast-like cell proliferation at certain concentration range throughout the 6-day culture period.

Incorporation and Immunogenicity of Cleaned Bovine Bone in a Sheep Model

Katz, J., Mukherjee, N., Cobb, R. R., Bursac, P., York-Ely, A. — Wed, 02 Sep 2009 06:18:30 PDT

This study was conducted to determine if a novel cleaning process could extract antigenic material from bovine bone thereby improving incorporation. Cleaned bovine xenograft, untreated bovine xenograft and sheep allograft were implanted into the tibia of mature sheep for 12 and 24 weeks. Inflammation, bone integration and immunological reactions were evaluated via standardized assays. Cleaned bovine bone dowels induced significantly lower inflammatory responses (p<50.05) when compared to traditionally processed xenograft. Bone integration, measured by in situ biomechanics, was not different between cleaned bovine bone and allograft controls (p = 0.96). A transient antibody response was observed for non-treated xenografts although this response abated by 3 months.

Free Bioverit (R) II Implants Coated with a Nanoporous Silica Layer in a Mouse Ear Model -- A Histological Study

Wed, 02 Sep 2009 06:18:30 PDT

The objective of this study is to evaluate the suitability of a mouse middle ear model for testing ossicular replacement materials. Twenty-four BALB/c mice are implanted with the bioglass-ceramic Bioverit^® II which is coated with a silica-nanostructure or with plain Bioverit^® II as a control. After 2, 6, and 12 weeks, 4 mice per group are sacrificed and both complete petrous bones are analyzed histologically. All implants revealed in situ an incipient growth of thin connective tissue layers over the surface, followed by a spreading of epithelial cells. The osseogenic response which is increasing with time is more intense in the coated Bioverit^® II specimens. The absence of inflammatory cells suggests an excellent biocompatibility of the silica nano structure. As the results are comparable to a study with the same materials in rabbits, the mouse model described is highly suitable for evaluation of new ossicular replacement materials. Additionally, by gene expression analysis a more detailed insight into cellular interactions of the middle ear is offered.

Editorial

Knowles, J. — Mon, 29 Jun 2009 03:36:07 PDT

Review Paper: A Review of the Cellular Response on Electrospun Nanofibers for Tissue Engineering

Nisbet, D.R., Forsythe, J.S., Shen, W., Finkelstein, D.I., Horne, M.K. — Mon, 29 Jun 2009 03:36:07 PDT

Electrospinning has been employed extensively in tissue engineering to generate nanofibrous scaffolds from either natural or synthetic biodegradable polymers to simulate the cellular microenvironment. Electrospinning rapidly produces fibers of the nanolength scale and the process offers many opportunities to tailor the physical, chemical, and biological properties of a material for specific applications and cellular environments. There is growing evidence that nanofibers amplify certain biological responses such as contact guidance and differentiation, however this has not been fully exploited in tissue engineering. This review addresses the cellular interactions with electrospun scaffolds, with particular focus on neural, bone, cartilage, and vascular tissue regeneration. Some aspects of scaffold design, including architectural properties, surface functionalization and materials selection are also addressed.

Development of Nanohydroxyapatite/Polycarbonate Composite for Bone Repair

Mon, 29 Jun 2009 03:36:07 PDT

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 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.

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

Ravikumara, N.R., Madhusudhan, B., Nagaraj, T.S., Hiremat, S. R., Raina, G. — Mon, 29 Jun 2009 03:36:07 PDT

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 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

Mon, 29 Jun 2009 03:36:07 PDT

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 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 spray-drying 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-g 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 immunoadjuvant to be used as antigen carriers for immunopotentiation.