Description

Biomaterials is an international journal covering the science and application of biomaterials and associated medical devices. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review papers dealing with the most important issues facing the use of materials in clinical practice. The scope of the journal covers the basic science and engineering aspects of biomaterials, including their mechanical, physical, chemical and biological properties, relevant design and production characteristics of devices constructed of these materials, and their clinical performance. In this context, biomaterials are defined as all those materials used in medical devices in which contact with the tissues of the patient is an important and guiding feature of their use and performance. They include a range of metals and alloys, glasses and ceramics, polymers, composites and natural or tissue-derived materials, including combinations of synthetic materials and living tissue components.

Publisher details

Elsevier

Publications in this journal

• Diminished adhesion and activation of platelets and neutrophils with CD47 functionalized blood contacting surfaces

  Authors: Matthew J Finley, Lubica Rauova, Ivan S Alferiev, John W Weisel, Robert J Levy, Stanley J Stachelek

  Biomaterials.

  a b s t r a c t CD47 is a ubiquitously expressed transmembrane protein that, through signaling mechanisms mediated by signal regulatory protein alpha (SIRPa1), functions as a biological marker ofa b s t r a c t CD47 is a ubiquitously expressed transmembrane protein that, through signaling mechanisms mediated by signal regulatory protein alpha (SIRPa1), functions as a biological marker of 'self-recognition'. We showed previously that inammatory cell attachment to polymeric surfaces is inhibited by the attachment of biotinylated recombinant CD47 (CD47B). We test herein the hypothesis that CD47 modied blood conduits can reduce platelet and neutrophil activation under clinically relevant condi-tions. We appended a poly-lysine tag to the C-terminus of recombinant CD47 (CD47L) allowing for covalent linkage to the polymer. SIRPa1 expression was conrmed in isolated platelets. We then compared biocompatibility between CD47B and CD47L functionalized polyvinyl chloride (PVC) surfaces and unmodied control PVC surfaces. Quantitative and Qualitative analysis of blood cell attachment to CD47B and CD47L surfaces, via scanning electron microscopy, showed strikingly fewer platelets attached to CD47 modied surfaces compared to control. Flow cytometry analysis showed that activation markers for neutrophils (CD62L) and platelets (CD62P) exposed to CD47 modied PVC were equivalent to freshly acquired control blood, while signicantly elevated in the unmodied PVC tubing. In addition, ethylene oxide gas sterilization did not inhibit the efcacy of the CD47 modication. In conclusion, CD47 modied PVC inhibits both the adhesion and activation of platelets and neutrophils.

• Construction and in vivo vascularisation of large diameter tubular scaffolds for gastrointestinal regenerative medicine

  Authors: M.J.W.Koens, P.J.Geutjes, H.R.Hoogenkamp, H. Ainodhofer, R.J.Wismans, D.M. Tiemessen, K.A. Faraj, et al.

  Biomaterials.

• Silk protein fibroin from Antheraea mylitta for cardiac tissue engineering

  Authors: Patra C, Talukdar S, Novoyatleva T, Velagala SR, Mühlfeld C, Kundu B, Kundu SC, Engel FB.

  Biomaterials.

  The human heart cannot regenerate after an injury. Lost cardiomyocytes are replaced by scar tissue resulting in reduced cardiac function causing high morbidity and mortality. One possible solution toThe human heart cannot regenerate after an injury. Lost cardiomyocytes are replaced by scar tissue resulting in reduced cardiac function causing high morbidity and mortality. One possible solution to this problem is cardiac tissue engineering. Here, we have investigated the suitability of non-mulberry silk protein fibroin from Indian tropical tasar Antheraea mylitta as a scaffold for engineering a cardiac patch in vitro. We have tested cell adhesion, cellular metabolic activity, response to extracellular stimuli, cell-to-cell communication and contractility of 3-days postnatal rat cardiomyocytes on silk fibroin. Our data demonstrate that A. mylitta silk fibroin exhibits similar properties as fibronectin, a component of the natural matrix for cardiomyocytes. Comparison to mulberry Bombyx mori silk protein fibroin shows that A. mylitta silk fibroin is superior probably due to its RGD domains. 3D scaffolds can efficiently be loaded with cardiomyocytes resulting in contractile patches. In conclusion, our findings demonstrate that A. mylitta silk fibroin 3D scaffolds are suitable for the engineering of cardiac patches.

• Tunable chemistry and morphology of MWCNTs as a route towards non-toxic theranostic systems

  Authors: S. Boncel, K. H. Müller, J. N. Skepper, K. Z. Walczak, K. K. K. Koziol

  Biomaterials. 32:7677.

• The effect of hydrophilic chain length and iRGD on drug delivery from poly(epsilon-caprolactone)-poly(N-vinylpyrrolidone) nanoparticles

  Authors: Zhu, ZS (Zhu, Zhenshu)1, Xie, C (Xie, Chen)1, Liu, Q (Liu, Qin)3, Zhen [......] Rutian)3, Ding, Y (Ding, Yin)4, Jiang, XQ (Jiang, Xiqun)1, Liu, BR (Liu, Baorui)3

  Biomaterials. 32:9525-9535.

• Fine-tuning DNA/albumin polyelectrolyte interactions to produce the efficient transfection agent cBSA-147.

  Authors: Eisele K, Gropeanu RA, Zehendner CM, Rouhanipour A, Ramanathan A, Mihov G, Koynov K, Kuhlmann CR, Vasudevan SG, Luhmann HJ, Weil T

  Biomaterials. 31:8789-801.

  We present the preparation and isolation of different chemically modified BSA species with varying numbers of primary amino groups at the surface. Highly cationic albumin proteins with increasedWe present the preparation and isolation of different chemically modified BSA species with varying numbers of primary amino groups at the surface. Highly cationic albumin proteins with increased numbers of amino groups were achieved and complex formation with plasmid DNA was carefully investigated. We compare the transfection results, polyelectrolyte complexes morphologies with their impact on complex stabilities, cytotoxicities and DNA accessibility. This knowledge-driven approach led to the identification of the efficient non-viral DNA delivery agent cBSA-147, which showed high transfection efficacies and stability.

• Finite element study of scaffold architecture design and culture conditions for tissue engineering

  Authors: Andy L. Olivares a, E ` lia Marsal b, Josep A. Planell a, Damien Lacroix a

  Biomaterials. 30.

• In vitro assessment of the pro-inflammatory potential of beta-hairpin peptide hydrogels.

  Authors: Lisa A Haines-Butterick, Daphne A Salick, Darrin J Pochan, Joel P Schneider

  Biomaterials. 29(31):4164-9.

  The pro-inflammatory potential of beta-hairpin peptide hydrogels (MAX1 and MAX8) was assessed in vitro by measuring the cellular response of J774 mouse peritoneal macrophages cultured on the hydrogelThe pro-inflammatory potential of beta-hairpin peptide hydrogels (MAX1 and MAX8) was assessed in vitro by measuring the cellular response of J774 mouse peritoneal macrophages cultured on the hydrogel surfaces. An enzyme-linked immunosorbent assay (ELISA) was used to measure the level of TNF-alpha, a pro-inflammatory cytokine, secreted by cells cultured on the gel surfaces. Both bulk and thin films of gels did not elicit TNF-alpha secretion from the macrophages. In addition, live/dead assays employing laser scanning confocal microscopy (LSCM) and phase-contrast light micrographs show the hydrogel surfaces are non-cytotoxic toward the macrophages and allow the cells to adopt healthy morphologies. When macrophages were activated with lipopolysaccharide (LPS), a known bacterial pathogen that activates an innate immune response, an increase in the TNF-alpha titers by two orders of magnitude was observed. On LPS induction, macrophages displayed a decrease in cell density, enlarged nuclei, and an increase in cytoplasmic granularity, all characteristics of activated macrophages indicating that the cells are still capable of reacting to insult. The data presented herein indicate that MAX1 and MAX8 gels do not elicit macrophage activation in vitro and suggest that these materials are excellent candidates for in vivo assessment in appropriate animal models.

• In vitro and in vivo suppression of cellular activity by guanidinoethyl disulfide released from hydrogel microspheres composed of partially oxidized hyaluronan and gelatin.

  Authors: Lihui Weng, Natalia D Ivanova, Julia Zakhaleva, Weiliam Chen

  Biomaterials. 29(31):4149-56.

  This paper describes the preparation of oxidized hyaluronan crosslinked gelatin microspheres for drug delivery. Microspheres were prepared by a modified water-in-oil-emulsion crosslinking method,This paper describes the preparation of oxidized hyaluronan crosslinked gelatin microspheres for drug delivery. Microspheres were prepared by a modified water-in-oil-emulsion crosslinking method, where three-dimensional crosslinked hydrogel microspheres formed in the absence of any extraneous crosslinker. SEM analyses of the microspheres showed rough surfaces in their dried state with an average diameter of 90mum. Lyophilization of fully swollen microspheres revealed a highly porous structure. Guanidinoethyl disulfide (GED) was used as a model drug for incorporation into the microspheres; encapsulation of GED was confirmed by HPLC. There was an inverse correlation between the diameters of the microspheres with their GED loading. Macrophage was used as a model cell to evaluate the in vitro efficacy of GED release from the microspheres. The in vivo efficacy of the microspheres was further validated in a mouse full-thickness transcutaneous dermal wound model through suppression of cell infiltration.

• Cell adhesion and proliferation on hydrophilic dendritically modified surfaces.

  Authors: Soumya R Benhabbour, Heather Sheardown, Alex Adronov

  Biomaterials. 29(31):4177-86.

  Dendritically modified, or "dendronized" surfaces are generated by modification of a substrate with perfectly branched polymers, known as dendrimers. Here, such dendronized surfaces were prepared byDendritically modified, or "dendronized" surfaces are generated by modification of a substrate with perfectly branched polymers, known as dendrimers. Here, such dendronized surfaces were prepared by initial chemisorption of poly(ethylene glycol)-mono-thiol (HS-PEG(650)-OH) onto gold-coated silicon wafers, followed by divergent synthesis of aliphatic polyester dendrons, generation 1-4, starting from the terminal PEG OH- group. The adhesion and proliferation of human corneal epithelial cells (HCEC) and mouse 3T3 fibroblasts (M-3T3) as model cells on these hydroxyl-terminated dendronized surfaces were investigated. In addition, the effect of covalently attaching PEG mono-methyl ether (PEG-OMe) chains (M(n)=2000Da) to the peripheral hydroxyl groups of G1- and G2-dendronized surfaces on adhesion and proliferation of the same cell lines was studied. Little or no HCEC adhesion was noted on gold surfaces modified with PEG mono-thiol (HO-PEG-SH) in serum-free medium. These cells showed a greater affinity for the dendronized surfaces compared to the control Au surfaces at early incubation stages (1 day). At longer incubation times, HCEC proliferation increased exponentially on the dendronized surfaces. However, when G1- and G2-dendronized surfaces were modified with PEG-OMe chains, adhesion of both HCEC and M-3T3 cells was significantly reduced. Cell studies with M-3T3 fibroblasts, carried out in serum-containing medium, showed that cell attachment was diminished for the PEG-grafted Au surfaces compared to the control Au and G1-G4 dendronized surfaces.

• Enrichment of undifferentiated mouse embryonic stem cells on a culture surface with a glucose-displaying dendrimer.

  Authors: Shohreh Mashayekhan, Mee-Hae Kim, Satsuki Miyazaki, Fumi Tashiro, Masahiro Kino-Oka, Masahito Taya, Jun-ichi Miyazaki

  Biomaterials. 29(31):4236-43.

  This article describes an in vitro culture system for embryonic stem (ES) cells, which are expected to serve as a cell source for transplantation because of their potential for indefinite expansionThis article describes an in vitro culture system for embryonic stem (ES) cells, which are expected to serve as a cell source for transplantation because of their potential for indefinite expansion and pluripotency. We present a serial passaging protocol that permits the enrichment of undifferentiated ES cells by culturing them on a surface modified with a synthesized dendrimer having d-glucose as a functional ligand. The d-glucose-displaying dendrimer (GLU/D) surface caused mouse ES cells to form loosely attached spherical colonies, and the frequency of such colonies increased gradually with the number of passages. Analyses of alkaline phosphatase activity and the gene expression of pluripotency and early differentiation markers revealed that the spherical colony cells passaged four times (a total of 16days in culture) on the GLU/D surface acquired more of the characteristics of undifferentiated cells than the cells cultured on a conventional gelatin-coated surface. Moreover, the cells cultured on the GLU/D surface retained their germ-line transmission ability after four passages. These results indicate that this modified culture surface may be a useful tool for obtaining enriched preparations of undifferentiated ES cells.

• Mechanisms of unmodified CdSe quantum dot-induced elevation of cytoplasmic calcium levels in primary cultures of rat hippocampal neurons.

  Authors: Mingliang Tang, Ming Wang, Tairan Xing, Jie Zeng, Huili Wang, Di-Yun Ruan

  Biomaterials. 29(33):4383-91.

  Quantum dots (QDs) have shown great promise for applications in biology and medicine, which is being challenged by their potential nanotoxicity. Reactive oxygen species (ROS) produced by QDs areQuantum dots (QDs) have shown great promise for applications in biology and medicine, which is being challenged by their potential nanotoxicity. Reactive oxygen species (ROS) produced by QDs are believed to be partially responsible for QD cytotoxicity. Cytoplasmic Ca(2+) plays an important role in the development of ROS injury. Here we found unmodified cadmium selenium (CdSe) QDs could elevate cytoplasmic calcium levels ([Ca(2+)](i)) in primary cultures of hippocampal neurons, involved both extracellular Ca(2+) influx and internal Ca(2+) release. More specifically, verapamil and mibefradil (L-type and T-type calcium channels antagonists, respectively) failed to prevent extracellular Ca(2+) influx under QD insult, while omega-conotoxin (N-type antagonist) could partially block this Ca(2+) influx. Surprisingly, this Ca(2+) influx could be well blocked by voltage-gated sodium channels (VGSCs) antagonist, tetrodotoxin (TTX). QD-induced internal Ca(2+) release could be avoided by clonazepam, a specific inhibitor of mitochondrial sodium-calcium exchangers (MNCX), and also by TTX. Furthermore, dantrolene, an antagonist of ryanodine (Ry) receptors in endoplasmic reticulum (ER), almost abolished internal Ca(2+) release, while 2-APB [inositol triphosphate (IP(3)) receptors antagonist] failed to block this Ca(2+) release, indicating that released Ca(2+) from mitochondria, which was induced by extracellular Na(+) influx, further triggered much more Ca(2+) release from ER. Our results imply that more research on the biocompatibility and biosafety of QD is both warranted and necessary.

• Changes in pore morphology and fluid transport in compressed articular cartilage and the implications for joint lubrication.

  Authors: George W Greene, Bruno Zappone, Boxin Zhao, Olle Söderman, Daniel Topgaard, Gabriel Rata, Jacob N Israelachvili

  Biomaterials. 29(33):4455-62.

  Cartilage sections were cut from the middle zone of pig knee articular cartilage and attached to substrates in two different kinds of newly designed 'pressure cells', one for fluorescence the otherCartilage sections were cut from the middle zone of pig knee articular cartilage and attached to substrates in two different kinds of newly designed 'pressure cells', one for fluorescence the other for NMR measurements. The fluorescence cell was filled with buffer solution containing fluorescently marked 70kDa dextran which was allowed to diffuse into the cartilage pores. A second glass surface was then pressed down onto the thin cartilage sample under different loads (pressures), and the resulting compression (strain) and change in pore volume were measured as a function of time, simultaneously with measurements of the lateral diffusion and flow pattern of the dextran molecules using Fluorescence Recovery After Photobleaching (FRAP). Complementary experiments were made on the normal diffusion coefficients of pure electrolyte solutions (no dextran) in thicker cartilage sections with pulse-gradient NMR using a new pressure cell suitable for such measurements. Taken together our results show that the highly anisotropic structure of cartilage has a strong effect on the way fluid diffuses laterally and normally at different stages of compression. Our results also show how geometric constraints on a cartilage network and trapped high MW polymer such as HA during normal compressions are likely to affect both the normal and the lateral mobilities of polyelectrolytes and water.

• Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering.

  Authors: Yanzhong Zhang, Jayarama Reddy Venugopal, Adel El-Turki, Seeram Ramakrishna, Bo Su, Chwee Teck Lim

  Biomaterials. 29(32):4314-22.

  The development of bioinspired or biomimetic materials is essential and has formed one of the most important paradigms in today's tissue engineering research. This paper reports a novel biomimeticThe development of bioinspired or biomimetic materials is essential and has formed one of the most important paradigms in today's tissue engineering research. This paper reports a novel biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan (HAp/CTS) prepared by combining an in situ co-precipitation synthesis approach with an electrospinning process. A model HAp/CTS nanocomposite with the HAp mass ratio of 30wt% was synthesized through the co-precipitation method so as to attain homogenous dispersion of the spindle-shaped HAp nanoparticles (ca. 100x30nm) within the chitosan matrix. By using a small amount (10wt%) of ultrahigh molecular weight poly(ethylene oxide) (UHMWPEO) as a fiber-forming facilitating additive, continuous HAp/CTS nanofibers with a diameters of 214+/-25nm had been produced successfully and the HAp nanoparticles with some aggregations were incorporated into the electrospun nanofibers. Further SAED and XRD analysis confirmed that the crystalline nature of HAp remains and had survived the acetic acid-dominant solvent system. Biological in vitro cell culture with human fetal osteoblast (hFOB) cells for up to 15 days demonstrated that the incorporation of HAp nanoparticles into chitosan nanofibrous scaffolds led to significant bone formation oriented outcomes compared to that of the pure electrospun CTS scaffolds. The electrospun nanocomposite nanofibers of HAp/CTS, with compositional and structural features close to the natural mineralized nanofibril counterparts, are of potential interest for bone tissue engineering applications.

• The behavior of aged regenerated Bombyx mori silk fibroin solutions studied by (1)H NMR and rheology.

  Authors: Zainuddin, Tri T. Le, Yoosup Park, Traian V. Chirila, Peter J. Halley, Andrew K. Whittaker

  Biomaterials. 29(32):4268-74.

  As part of a project to utilize the regenerated silk fibroin (RSF) membranes as a supporting matrix for the attachment and growth of corneal stem/progenitor cells in the development of tissueAs part of a project to utilize the regenerated silk fibroin (RSF) membranes as a supporting matrix for the attachment and growth of corneal stem/progenitor cells in the development of tissue engineered constructs for the surgical restoration of the ocular surface, the behavior of the aged RSF solutions has been investigated. The solutions were produced from domesticated silkworm (Bombyx mori) cocoons according to a protocol involving successive dissolution steps, filtration and dialysis. The solutions were kept at 4 degrees C in a refrigerator for a certain period of time until near the gelation time. The changes in molecular conformation were studied by solution-state (1)H NMR, while the flow of the solutions was characterized by rheological method. Upon ageing turbidity developed in solutions and the viscosity continuously decreased prior to a drastic increased near the gelation time. The (1)H resonances of aged solutions showed a consistent downfield shift as compared to the (1)H resonances of the fresh solution. Shear thinning with anomalous short recovery within a certain range of low shear rates occurred in both fresh and aged solutions. While the solutions behave as pseudo-plastic materials, the chain conformation in aged solutions adopted all secondary configurations with beta-strand being predominant.

• The influence of RGD addition on the gene transfer characteristics of disulfide-containing polyethyleneimine/DNA complexes.

  Authors: Yun-Xia Sun, Xuan Zeng, Qing-Fei Meng, Xian-Zheng Zhang, Si-Xue Cheng, Ren-Xi Zhuo

  Biomaterials. 29(32):4356-65.

  Arginine-glycine-aspartic acid (RGD) ligand is often chemically attached to polycation vector to improve the transfection efficiency. However, the chemical reaction may reduce or even inactivate theArginine-glycine-aspartic acid (RGD) ligand is often chemically attached to polycation vector to improve the transfection efficiency. However, the chemical reaction may reduce or even inactivate the biological activities of peptides. In order to retain the targeting ability and biological activities, the RGD peptide was noncovalently introduced into polycations as gene delivery systems. In this paper, the tripeptide sequence RGD was added to disulfide-containing polyethyleneimine (SS-PEI)/DNA binary complexes to evaluate the influence of RGD addition for the particle size, zeta potential, morphology, and transfection efficiency. GelRedtrade mark was used as a molecular probe to show the effect of RGD addition on the cellular uptake of complexes. In vitro transfection experiments showed that SS-PEI exhibited comparable transfection efficiency, but lower cytotoxicity in comparison with 25kDa PEI. The transfection efficiency of complexes with RGD in HeLa cells was reduced statistically significantly with the increasing content of RGD peptide, but that in 293T cells was not altered significantly with the increasing content of RGD peptide. The reduced transfection efficiency of SS-PEI/DNA complexes with RGD in HeLa cells was attributed to the targeted binding interactions between the surplus RGD and the alpha(nu)beta(3) and alpha(nu)beta(5) integrins in HeLa cells, which would prevent the binding between RGD in complexes and integrin receptor on the surface of cells as well as nonspecific endocytosis of SS-PEI/DNA complexes mediated by proteoglycan in HeLa cells.

• Porous collagen-apatite nanocomposite foams as bone regeneration scaffolds.

  Authors: Y S Pek, Shujun Gao, M S Mohamed Arshad, Kwong-Joo Leck, Jackie Y Ying

  Biomaterials. 29(32):4300-5.

  We have created a porous bioresorbable nanocomposite bone scaffold that chemically, structurally and mechanically matched natural bone so that it could be recognized and remodeled by natural bone.We have created a porous bioresorbable nanocomposite bone scaffold that chemically, structurally and mechanically matched natural bone so that it could be recognized and remodeled by natural bone. Containing collagen fibers and synthetic apatite nanocrystals, our scaffold has high strength for supporting the surrounding tissue. The foam-like scaffold has a similar microstructure as trabecular bone, with nanometer-sized and micron-sized pores. The apatitic phase of the scaffold exhibited similar chemical composition, crystalline phase and grain size as the trabecular bone apatite. The nanocomposite scaffold demonstrated excellent bioactivity for promoting cell attachment and proliferation. It was osteoconductive and successfully healed a non-union fracture in rat femur as well as a critical-sized defect in pig tibia.

• Aqueous solution behaviour and membrane disruptive activity of pH-responsive PEGylated pseudo-peptides and their intracellular distribution.

  Authors: Rongjun Chen, Zhilian Yue, Mark E Eccleston, Nigel K H Slater

  Biomaterials. 29(32):4333-40.

  The effect of PEGylation on the aqueous solution properties and cell membrane disruptive activity of a pH-responsive pseudo-peptide, poly(l-lysine iso-phthalamide), has been investigated by dynamicThe effect of PEGylation on the aqueous solution properties and cell membrane disruptive activity of a pH-responsive pseudo-peptide, poly(l-lysine iso-phthalamide), has been investigated by dynamic light scattering, haemolysis and lactate dehydrogenase (LDH) assays. Intracellular trafficking of the polymers has been examined using confocal and fluorescence microscopy. With increasing degree of PEGylation, the modified polymers can form stabilised compact structures with reduced mean hydrodynamic diameters. Poly(l-lysine iso-phthalamide) with a low degree of PEGylation (17.4wt%) retained pH-dependent solution behaviour and showed enhanced kinetic membrane disruptive activity compared to the parent polymer. It facilitated trafficking of endocytosed materials into the cytoplasm of HeLa cells. At levels of PEGylation in excess of 25.6wt%, the modified polymers displayed a single particle size distribution unresponsive to pH, as well as a decrease in cell membrane lytic ability. The mechanism involved in membrane destabilisation was also investigated, and the potential applications of these modified polymers in drug delivery were discussed.

• Strength and fluoride release characteristics of a calcium fluoride based dental nanocomposite.

  Authors: Hockin H K Xu, Jennifer L Moreau, Limin Sun, Laurence C Chow

  Biomaterials. 29(32):4261-7.

  Secondary caries and restoration fracture remain the two most common problems in restorative dentistry. Release of fluoride ions (F) could be a substantial benefit because F could enrich neighboringSecondary caries and restoration fracture remain the two most common problems in restorative dentistry. Release of fluoride ions (F) could be a substantial benefit because F could enrich neighboring enamel or dentin to combat caries. The objective of this study was to incorporate novel CaF(2) nanoparticles into dental resin to develop stress-bearing, F-releasing nanocomposite. CaF(2) nanoparticles, prepared in our laboratories for the first time, were combined with reinforcing whisker fillers in a resin. Flexural strength (mean+/-sd; n=6) was 110+/-11MPa for the composite containing 30% CaF(2) and 35% whiskers by mass. It matched the 108+/-19MPa of a stress-bearing, non-releasing commercial composite (Tukey's at 0.05). The composite containing 20% CaF(2) had a cumulative F release of 2.34+/-0.26mmol/L at 10weeks. The initial F release rate was 2mug/(hcm(2)), and the sustained release rate after 10weeks was 0.29mug/(hcm(2)). These values exceeded the reported releases of traditional and resin-modified glass ionomer materials. In summary, nanocomposites were developed with relatively high strength as well as sustained release of fluoride ions, a combination not available in current materials. These strong and F-releasing composites may yield restorations that can reduce the occurrence of both secondary caries and restoration fracture.

• Adhesion forces between Staphylococcus epidermidis and surfaces bearing self-assembled monolayers in the presence of model proteins.

  Authors: Yatao Liu, Joshua Strauss, Terri A Camesano

  Biomaterials. 29(33):4374-82.

  Self-assembled monolayers (SAMs) are being developed into coatings to reduce microbial biofilm formation on biomaterials. To test anti-adhesion properties, SAMs can be easily constructed on gold, andSelf-assembled monolayers (SAMs) are being developed into coatings to reduce microbial biofilm formation on biomaterials. To test anti-adhesion properties, SAMs can be easily constructed on gold, and used to represent a coated biomaterial. However, coatings that prevent bacterial adhesion must also resist protein adsorption. We explored the competitive effects of bacteria and protein for adsorption to SAMs, choosing fetal bovine serum (FBS) to represent protein non-specific binding, and fibronectin (FN) to evaluate ligand/receptor binding. Staphylococcus epidermidis were immobilized on an atomic force microscope (AFM) tip and used as a force probe to detect the interaction forces between bacteria and gold-coated SAMs. The SAMs tested were alkanethiol molecules terminating in isophthalic acid (IPA) or isophthalic acid with silver (IAG). While S. epidermidis showed weak interactions with FBS, the bacteria showed strong adhesion with FN, due to ligand/receptor binding. Bacterial retention and viability experiments were correlated with the force measurements. S. epidermidis interacting with IAG SAMs showed a loss of viability, due to the mobility of silver ions. For most substrata, there was a link between high adhesion forces with bacteria and a high percentage of dead cells being retained on that substratum (even in the absence of a specific biocidal effect, such as silver). This may suggest that high adhesion forces can cause stress to the bacteria which contributed to their death. The relationship between highly adhesive SAMs and bacterial inactivation may be useful in future biomaterial design. When evaluating coatings for biomaterials, it is important to consider the interplay between bacteria, proteins, and the coating material.

• A biodegradable, immunoprotective, dual nanoporous capsule for cell-based therapies.

  Authors: Xulang Zhang, Hongyan He, Chi Yen, Wiston Ho, L James Lee

  Biomaterials. 29(31):4253-9.

  To demonstrate the transplantation of drug-secreting cells with immunoprotection, a biodegradable delivery device combining two nanoporous capsules is developed using secretory alkaline phosphataseTo demonstrate the transplantation of drug-secreting cells with immunoprotection, a biodegradable delivery device combining two nanoporous capsules is developed using secretory alkaline phosphatase gene (SEAP) transfected mouse embryonic stem (mES) cells as a model system. The outer capsule is a poly (ethylene glycol) (PEG)-coated poly (varepsilon-caprolactone) (PCL) chamber covered with a PEG grafted PCL nanoporous membrane made by phase inversion technique. SEAP gene transfected mES cells encapsulated in alginate-poly-l-lysine (AP) microcapsules are placed in the PCL capsule. Both nanoporous capsules showed good immunoprotection in the IgG solution. In microcapsules, mES cells could form a spheroid embryonic body (EB) and grow close to the microcapsule size. The secreted SEAP from encapsulated mES cells increased gradually to a maximum value before reaching a steady level, following the cell growth pattern in the microcapsule. Without microcapsules, mES cells only formed a monolayer in the large PCL capsule. The secreted SEAP release was very low. The integrated device showed a similar cell growth pattern to that in microcapsules alone, while the SEAP release rate could be regulated by the pore size of the large capsule. This integrated device can achieve multi-functionalities for cell-based therapy, i.e. a 3-D microenvironment provided by microcapsules for cell growth, superior immunoprotection and controllable release performance provided by the two nanoporous membranes, and good fibrosis prevention by PEG surface modification of the large capsule.

• Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model.

  Authors: S Amado, M J Simões, P A S Armada da Silva, A L Luís, Y Shirosaki, M A Lopes, J D Santos, F Fregnan, G Gambarotta, S Raimondo, M Fornaro, A P Veloso, A S P Varejão, A C Maurício, S Geuna

  Biomaterials. 29(33):4409-19.

  Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to use inMany studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to develop and test hybrid chitosan membranes to use in peripheral nerve reconstruction, either alone or enriched with N1E-115 neural cells. Hybrid chitosan membranes were tested in vitro, to assess their ability in supporting N1E-115 cell survival and differentiation, and in vivo to assess biocompatibility as well as to evaluate their effects on nerve fiber regeneration and functional recovery after a standardized rat sciatic nerve crush injury. Functional recovery was evaluated using the sciatic functional index (SFI), the static sciatic index (SSI), the extensor postural thrust (EPT), the withdrawal reflex latency (WRL) and ankle kinematics. Nerve fiber regeneration was assessed by quantitative stereological analysis and electron microscopy. All chitosan membranes showed good biocompatibility and proved to be a suitable substrate for plating the N1E-115 cellular system. By contrast, in vivo nerve regeneration assessment after crush injury showed that the freeze-dried chitosan type III, without N1E-115 cell addition, was the only type of membrane that significantly improved posttraumatic axonal regrowth and functional recovery. It can be thus suggested that local enwrapping with this type of chitosan membrane may represent an effective approach for the improvement of the clinical outcome in patients receiving peripheral nerve surgery.

• Molecular dynamics study of heparin based coatings.

  Authors: Martin Almlöf, Emma M E Kristensen, Hans Siegbahn, Johan Aqvist

  Biomaterials. 29(33):4463-9.

  Heparin based surface coatings can be used to improve the biocompatibility of metallic surfaces such as vascular stents. Here, we report molecular dynamics simulations of a macromolecular conjugateHeparin based surface coatings can be used to improve the biocompatibility of metallic surfaces such as vascular stents. Here, we report molecular dynamics simulations of a macromolecular conjugate of heparin used to prepare such surfaces. The structural properties of the heparin conjugate are investigated for different degrees of hydration, to allow comparison with spectroscopic results. The simulations show that the polymer becomes more compact with an increasing degree of inter-chain interactions as the hydration increases. This is also accompanied by changes in the interaction patterns among the heparin chains, where counter ions become looser associated with the disaccharide units and their strong interactions can be partly replaced by water molecules and heparin hydroxyl groups. The structural information that can be obtained from computer simulations of this type of coatings can be very valuable for understanding and further development of functional interfaces, since very little is known experimentally regarding their detailed structural properties.

• The osteogenic differentiation of rat muscle-derived stem cells in vivo within in situ-forming chitosan scaffolds.

  Authors: Kyung Sook Kim, Jung Hwa Lee, Hyun Hee Ahn, Ju Young Lee, Gilson Khang, Bong Lee, Hai Bang Lee, Moon Suk Kim

  Biomaterials. 29(33):4420-4428.

  We herein examined the bone formation from rat muscle-derived stem cells (rMDSCs) using an injectable in situ-forming chitosan gel in vivo. The rMDSCs were easily isolated from rat muscle tissue. TheWe herein examined the bone formation from rat muscle-derived stem cells (rMDSCs) using an injectable in situ-forming chitosan gel in vivo. The rMDSCs were easily isolated from rat muscle tissue. The osteogenic factors caused differentiation of rMDSCs toward the osteogenic lineage. The rMDSCs survived well on the scaffold created by the in vitro and in vivo in situ-forming chitosan gel, indicating that in situ gel-forming chitosan was a suitable substrate for the attachment and proliferation of rMDSCs. Bone formation was observed only in chitosan gel containing both rMDSCs and osteogenic factors. Subcutaneous implantation of the in situ-forming chitosan gel demonstrated that rMDSCs-containing chitosan gel induced much lower host tissue responses than did the chitosan gel alone, probably due to the immunosuppression of the transplanted rMDSCs.

• Essential role of structural integrity and firm attachment of surface-anchored epidermal growth factor in adherent culture of neural stem cells.

  Authors: Tadashi Nakaji-Hirabayashi, Koichi Kato, Hiroo Iwata

  Biomaterials. 29(33):4403-8.

  Surface immobilization of proteins provides various biomaterials that permit the control of cellular functions through protein-protein interactions. Our previous study demonstrated that humanSurface immobilization of proteins provides various biomaterials that permit the control of cellular functions through protein-protein interactions. Our previous study demonstrated that human epidermal growth factor carrying a hexahistidine sequence at the C-terminus (hEGF-His) could be anchored to the Ni-chelated surface by coordination, providing the versatile substrate for the selective proliferation of neural stem cells. The present study was undertaken to gain deeper insights into the basis for such an outstanding property of the surface with coordinated hEGF-His. For this purpose, the structure of the coordinated hEGF-His was analyzed by multiple internal reflection-infrared absorption spectroscopy. In addition, stability of coordinate bonds was assessed under cell culture conditions using a spatially-restricted anchoring technique. These data were compared to the results obtained from surfaces with covalently immobilized and physically adsorbed hEGF-His. The results presented here demonstrate that coordinated hEGF-His remains its intact conformation and is firmly anchored to the surface during cell culture. These attributes are both crucial for establishing the adherent culture and hence selective expansion of neural stem cells.

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.