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Biomaterial associated impairment of local neutrophil function
Kaplan, S. S., R. E. Basford, et al. (1990), ASAIO Trans 36(3): M172-5.
Abstract: The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

Biomaterial biocompatibility and the macrophage
Anderson, J. M. and K. M. Miller (1984), Biomaterials 5(1): 5-10.
Abstract: The biocompatibility of biomaterials at implant sites is controlled by the tissue/material interaction. A major cell in the tissue reaction is the macrophage. A summary is presented on macrophage mediation of cellular and humoral regulatory pathways in inflammatory and immune responses.

Biomaterial biotechnology using self-assembled lipid microstructures
Rudolph, A. S. (1994), J Cell Biochem 56(2): 183-7.
Abstract: Lipids are a class of molecules which self-assemble into a variety of phase-dependent morphologies. We have employed self-assembled lipid microstructures in the development of a number of biomedical material applications. The blood substitute, liposome encapsulated hemoglobin, is being investigated for the in vivo delivery of hemoglobin without many of the inherent toxicities associated with the delivery of free hemoglobin. This investigation is currently focused on demonstrations of efficacy in stressed animal models and on the safety of administering this material in models of sepsis. The synthetic modification of phospholipids to include photopolymerizable moieties such as diacetylenes has resulted in the spontaneous self-assembly of a hollow microcylinder which we are investigating for the controlled release of growth factors in soft tissue regeneration. Self-assembled monolayers are also being explored for the ability to surface modify biomaterials for improved cell adhesion. Photolithographic techniques have been combined with monolayer deposition to fabricate coplanar patterns of cell adhesion and inhibiting moieties. This results in the ability to spatially control the adhesion of cells to biomaterial surfaces. These cell patterns can form the basis for understanding two- and three-dimensional cellular events on the biomaterial surface and for the fabrication of improved cell-based biocompatible surfaces. The spontaneous self-assembly of lipids to form structures of biotechnological interest presents a unique opportunity to exploit this class of molecules for biomaterial applications.

Biomaterial calcification without direct material-cell interaction
Shumakov, V. I., I. B. Rosanova, et al. (1990), ASAIO Trans 36(3): M181-4.
Abstract: This report summarizes 1) features of the local redistribution of calcium ions and formation of complexes with calcium (Ca) in the presence of polymer samples; 2) the adsorption of Ca ions and Ca containing complexes onto biomaterial surfaces; 3) the character and composition of Ca containing deposits; and 4) the role of cellular and humoral factors in calcification. All experiments were done with three types of medical grade polymer material (from USSR): silicone rubber (SR), polyurethane "Vitur" (PU), and polyethylene (PE). Biochemical, radioisotopic, SEM, and EDAX methods were used in in vitro and in vivo experiments. The diffusion chamber model was used in animal experiments. SR was shown to induce greater changes in complex formation processes and to adsorb more Ca containing complexes than PE or PU. In addition to the degree of SR calcification seen after 21 days, implantation accentuated these findings. The possibility of calcification of polymer materials without direct contact of material and cells was observed. Combining the in vitro and in vivo experimental data, the authors propose a hypothetical scheme of biomaterial calcification.

Biomaterial challenges and approaches to stem cell use in bone reconstructive surgery
Olivier, V., N. Faucheux, et al. (2004), Drug Discov Today 9(18): 803-11.
Abstract: As life expectancy increases, so does the need to treat large bone defects. New biomaterials combined with osteogenic cells are now being developed as an alternative to autogenous bone grafts. The goal is to make the stem cells adhere to the scaffold, and then grow to differentiate into functional osteogenic cells and organize into healthy bone as the scaffold degrades. Decisive improvements have been made in the fields of stem cell biology, 3-D scaffold fabrication and tissue engineering, but the ideal bone substitute that fulfils all functional and safety requirements has yet to be developed.

Biomaterial characteristics important to skeletal tissue engineering
Lim, J. Y. and H. J. Donahue (2004), J Musculoskelet Neuronal Interact 4(4): 396-8.

Biomaterial coatings by stepwise deposition of silk fibroin
Wang, X., H. J. Kim, et al. (2005), Langmuir 21(24): 11335-41.
Abstract: A completely aqueous, stepwise deposition process with Bombyx mori silk fibroin for the assembly of nanoscale thin film coatings is reported the first time. The focus of this work was to develop an understanding of the control of this deposition process and to characterize the films formed from a physicochemical perspective. The deposition process was monitored by UV spectrophotometry and research quartz crystal microbalance. Both absorbance and film thickness correlated linearly with the number of silk fibroin layers deposited, analogous to multilayered materials fabricated from conventional polyelectrolytes. The polymer adsorption process was stable and reproducible, with control of a single layer thickness ranging from a few to tens of nanometers, determined by the concentrations of silk fibroin, salt concentration in the dipping solution, and method of rinsing. The driving force for the assembly of silk fibroin onto the substrate was primarily hydrophobic interactions, while some electrostatic interactions were also involved. The difference with this approach from traditional polyelectrolyte layer-by-layer techniques is that an intervening drying step is used to control the structure and stability of the self-assembled silk fibroin. The assembled films were stable under physiological conditions and supported human bone marrow stem cell adhesion, growth, and differentiation. This approach offers new options to engineer biomaterial coatings as well as bulk materials with control of both interfacial properties conducive to specific cellular or tissue responses and the potential to entrap and deliver labile molecules or other components due to the all-aqueous process described.

Biomaterial considerations for dental implants part I: metals and alloys
Lemons, J. E. (1975), Oral Implantol 5(4): 503-15.

Biomaterial considerations for the optimized therapy for the edentulous predicament
Glantz, P. O. (1998), J Prosthet Dent 79(1): 90-2.
Abstract: A range of biomaterials are used in rendering prosthodontic treatment for the completely edentulous patient. This article reviews the biomaterials considerations in the use of metals and metal alloys, ceramics and carbons, and synthetic materials for implant therapy. It also discusses implant material selection, biomaterial aspects of bioadhesion, and osseointegration and hygiene-related biomaterial factors.

Biomaterial development for cardiopulmonary bypass
Gourlay, T. (2001), Perfusion 16(5): 381-90.
Abstract: Cardiopulmonary bypass (CPB) is dependent on materials foreign to the patient for its successful application. When blood comes into contact with these so-called biomaterials, an inappropriate inflammatory response, which can be life-threatening in some patients, may develop. The reason for this inappropriate activation of host defence mechanisms is not entirely clear, however a number of strategies have evolved over the years to minimize this unwanted sequelae of CPB. These strategies include surface coating of the materials of the circuit, using new materials thought to improve biocompatibility, and using a number of pharmacological interventions designed to suppress the inflammatory response. Recently, there has been some evidence which indicates that the plasticizer employed in the polyvinyl chloride (PVC) tubing of the CPB circuit may play a part in the development of the inflammatory response. The work described in this paper tends to support this thesis. These studies showed that by washing the plasticizer from the surface of the PVC tubing, the biocompatibility, as reflected in the upregulation of CD11b on the surface of neutrophils, was enhanced. Furthermore, the use of non-plasticized substitutes for PVC had a similar effect. The benefit from removing the plasticizer was similar to that gained from surface coating with heparin, one of the conventional approaches to reducing the inflammatory response to CPB.

Biomaterial development in Russia and the independent states
Sevastianov, V. I. (1996), Asaio J 42(1): 4-7.

Biomaterial developments for bone tissue engineering
Burg, K. J., S. Porter, et al. (2000), Biomaterials 21(23): 2347-59.
Abstract: The development of bone tissue engineering is directly related to changes in materials technology. While the inclusion of materials requirements is standard in the design process of engineered bone substitutes, it is also critical to incorporate clinical requirements in order to engineer a clinically relevant device. This review presents the clinical need for bone tissue-engineered alternatives to the present materials used in bone grafting techniques, a status report on clinically available bone tissue-engineering devices, and recent advances in biomaterials research. The discussion of ongoing research includes the current state of osseoactive factors and the delivery of these factors using bioceramics and absorbable biopolymers. Suggestions are also presented as to the desirable design features that would make an engineered device clinically effective.

Biomaterial engineered electrodes for bioelectronics
Pardo-Yissar, V., E. Katz, et al. (2000), Faraday Discuss(116): 119-34; discussion 171-90.
Abstract: A series of single-cysteine-containing cytochrome c, Cyt c, heme proteins including the wild-type Cyt c (from Saccharomyces cerevisiae) and the mutants (V33C, Q21C, R18C, G1C, K9C and K4C) exhibit direct electrical contact with Au-electrodes upon covalent attachment to a maleimide monolayer associated with the electrode. With the G1C-Cyt c mutant, which includes the cysteine residue in the polypeptide chain at position 1, the potential-induced switchable control of the interfacial electron transfer was observed. This heme protein includes a positively charged protein periphery that surrounds the attachment site and faces the electrode surface. Biasing of the electrode at a negative potential (-0.3 V vs. SCE) attracts the reduced Fe(II)-Cyt c heme protein to the electrode surface. Upon the application of a double-potential-step chronoamperometric signal onto the electrode, where the electrode potential is switched to +0.3 V and back to -0.3 V, the kinetics of the transient cathodic current, corresponding to the re-reduction of the Fe(III)-Cyt c, is controlled by the time interval between the oxidative and reductive potential steps. While a short time interval results in a rapid interfacial electron-transfer, ket1 = 20 s-1, long time intervals lead to a slow interfacial electron transfer to the Fe(III)-Cyt c, ket2 = 1.5 s-1. The fast interfacial electron-transfer rate-constant is attributed to the reduction of the surface-attracted Fe(III)-Cyt c. The slow interfacial electron-transfer rate constant is attributed to the electrostatic repulsion of the positively charged Cyt c from the electrode surface, resulting in long-range electron transfer exhibiting a lower rate constant. At intermediate time intervals between the oxidative and reductive steps, two populations of Cyt c, consisting of surface-attracted and surface-repelled heme proteins, are observed. Crosslinking of a layered affinity complex between the Cyt c and cytochrome oxidase, COx, on an Au-electrode yields an electrically-contacted, integrated, electrode for the four-electron reduction of O2 to water. Kinetic analysis reveals that the rate-limiting step in the bioelectrocatalytic reduction of O2 by the integrated Cyt c/COx electrode is the primary electron transfer from the electrode support to the Cyt c units.

Biomaterial failure
Spector, M. (1992), Orthop Clin North Am 23(2): 211-7.
Abstract: One conclusion that might be drawn from a review of the role of biomaterial failure in total hip arthroplasty is that the fracture, wear, and corrosion of materials often serve as the primary causes of failure of hip replacements. It is not yet possible, however, to conclude the prevalence or time course of these failures. We need to gain more knowledge about the properties of orthopedic biomaterials and the loading to which they are subjected during function. Judicious design and implementation of prostheses can serve to extend the serviceable life of an arthroplasty even with ongoing fracture, wear, and corrosion of biomaterials.

Biomaterial films of Bombyx mori silk fibroin with poly(ethylene oxide)
Jin, H. J., J. Park, et al. (2004), Biomacromolecules 5(3): 711-7.
Abstract: Phase separation into controllable patterned microstructures was observed for Bombyx mori silkworm silk and poly(ethylene oxide) (PEO) (900000 g/mol) blends cast from solution. The evolution of the microstructures with increasing PEO volume fraction is strikingly similar to the progression of phases and microstructures observed with surfactants. The chemically patterned materials obtained provide engineerable biomaterial surfaces with predictable microscale features which can be used to create topographically patterned or chemically functionalized biomaterials. Solution blending was used to incorporate water-soluble PEO into silk to enhance elasticity and hydrophilicity. The sizes of the globule fibroin phase ranged from 2.1 +/- 0.5 to 18.2 +/- 2.1 microm depending on the ratio of silk/PEO. Optical microscopy and SEM analysis confirmed the micro-phase separation between PEO and silk. Surface properties were determined by XPS and contact angle. Methanol can be used to control the conformational transition of silk fibroin to the insoluble beta-sheet state. Subsequentially, the PEO can be easily extracted from the films with water to generate silk matrixes with definable porosity and enhanced surface roughness. These blend films formed from two biocompatible polymers provide potential new biomaterials for tissue engineering scaffolds.

Biomaterial implants induce the inflammation marker CRP at the site of implantation
Lobler, M., M. Sass, et al. (2002), J Biomed Mater Res 61(1): 165-7.
Abstract: Following implantation of biomaterial patches into the gastrointestinal tract, we analyzed the host's response towards the foreign material. Asymmetric patches of polydioxanone covered Vicryl or poly-3-hydroxybutyrate were sutured onto the rat stomach. Tissue samples were generated at distinct time intervals after surgery, and RNA profiles were compared by Differential Display. RT-PCR analysis of gene candidates that seemed differentially expressed showed that vitamin D binding protein mRNA was induced in stomach tissue after implantation of the biomaterial patches. In parallel, the amount of C-reactive protein mRNA was found to be increased transiently as well. Implants induce a tissue response that is specific for a given material.

Biomaterial mesh seeded with vascular remnants from a quail embryo has a significant and fast vascular templating effect on host implant tissue
Sanders, J. E., Y. N. Wang, et al. (2003), Tissue Eng 9(6): 1271-9.
Abstract: Seeding biomaterial implants with vascular remnants has the potential to facilitate host vessel ingrowth via a vascular templating effect. Vessels from quail embryo were grown into a polyurethane fibroporous mesh and the samples were frozen-thawed and then implanted in rat subcutaneous dorsum. Results show that the process of revascularization, using the quail vessel remnants, occurred over the first 3 days after implantation and resulted in functional vessels. Rat endothelial cells were found in the quail templates on day 1. On day 2 the endothelial cells formed a confluent layer and started producing laminin. By this time approximately 70% of the rat vessel tissue in the implant had grown into quail vascular remnants, indicating that the quail vessels were extensively used as templates for host vessel ingrowth. Laminin production was increased and collagen production started by day 3, at which time the vessels were functional in that rat blood flowed through them. At 2 weeks host vessel density was approximately twice that of control samples; thus the implant substantially enhanced the size of the vascular network. For meshes that additionally received vascular endothelial growth factor (VEGF) seeding before implantation, vessel density at 2 weeks was enhanced over samples with quail embryo alone. However, the quail was found to have the greatest angiogenic effect above any of the implant components-quail, VEGF, and collagen. Tissue engineering of vessel templates may thus be a realistic solution to effective fast vascularization of biomaterials.

Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction
Anderson, D. G., D. Putnam, et al. (2005), Biomaterials 26(23): 4892-7.
Abstract: The identification of biomaterials that induce optimal gene expression patterns and allow for appropriate levels of cellular attachment is of central importance in tissue engineering and cell therapy. Herein, we describe the creation of cell-compatible, biomaterial microarrays, that allow rapid, microscale testing of biomaterial interactions with cells. As proof of principle, we simultaneously characterized over 3456 human mesenchymal stem cell (hMSC)-biomaterial composite interactions, and describe preliminary studies on the utility of these arrays with a neural stem cell line (NSC), and primary articular chondrocytes.

Biomaterial optimization in total disc arthroplasty
Hallab, N., H. D. Link, et al. (2003), Spine 28(20): S139-52.
Abstract: STUDY: Knowledge gained through the clinical history of total joint replacement materials combined with the current promise of new biomaterials provides improved guidelines for biomaterial selection in total disc arthroplasty. OBJECTIVES: The following will detail: 1) current biomaterials technology; 2) how current designs of total disc arthroplasty seek to optimize implant performance through judicious biomaterial selection; and 3) what technical obstacles and clinical concerns remain. METHODS: Metals and polymers remain the central material components of state-of-the-art total joint arthroplasties. Polymers provide low friction surfaces for articulating bearings and some degree of shock absorption. Metals provide appropriate material properties such as high strength, ductility, fracture toughness, hardness, corrosion resistance, formability, and biocompatibility necessary for use in load-bearing roles required total disc replacement. There are three principal metal alloys used in orthopaedics and particularly in total joint replacement: 1) titanium based alloys; 2) cobalt based alloys; and 3) stainless steel alloys. Alloy specific differences in strength, ductility, and hardness generally determine which of these three alloys is used for a particular application or implant component. RESULTS: Current designs. Two examples of current lumbar (Charite and Prodisc) and cervical (Bryan and Prestige) disc replacements are compared. The similarities and differences in the biomaterials used for each demonstrate prevailing consensus and some idea of how to best optimize implant performance through biomaterial selection. CONCLUSION: The primary factors governing total disc arthroplasty biomaterials are similar to those of all total joint arthroplasties: generation of wear debris is the primary source of implant degradation, and the subsequent tissue reaction to such debris is the primary factor limiting the longevity of joint replacement prostheses. Particulate debris generated by wear, fretting, or fragmentation induces the formation of an inflammatory reaction, which at a certain point promotes a foreign-body granulation tissue response that has the ability to invade the bone-implant interface. This commonly results in progressive, local bone loss that threatens the fixation of both cemented and cementless devices alike. All metal alloy implants corrode in vivo. When severe, the degradative process may reduce structural integrity of the implant, and the release of corrosion products is potentially toxic to the host. The corrosion resistance of implant alloys is primarily due to the formation of passive oxide films to prevent significant electrochemical dissolution from taking place. The result of this knowledge is a consensus of opinion as to which materials are best suited for use in current total disc arthroplasty designs, where most total disc replacement designs incorporate cobalt-chromium-molybdenum alloy endplates articulating internally on a relatively soft polymeric core and externally coated with titanium or titanium alloy for enhanced bone fixation.

Biomaterial particle phagocytosis by bone-resorbing osteoclasts
Wang, W., D. J. Ferguson, et al. (1997), J Bone Joint Surg Br 79(5): 849-56.
Abstract: Abundant implant-derived biomaterial wear particles are generated in aseptic loosening and are deposited in periprosthetic tissues in which they are phagocytosed by mononuclear and multinucleated macrophage-like cells. It has been stated that the multinucleated cells which contain wear particles are not bone-resorbing osteoclasts. To investigate the validity of this claim we isolated human osteoclasts from giant-cell tumours of bone and rat osteoclasts from long bones. These were cultured on glass coverslips and on cortical bone slices in the presence of particles of latex, PMMA and titanium. Osteoclast phagocytosis of these particle types was shown by light microscopy, energy-dispersive X-ray analysis and SEM. Giant cells containing phagocytosed particles were seen to be associated with the formation of resorption lacunae. Osteoclasts containing particles were also calcitonin-receptor-positive and showed an inhibitory response to calcitonin. Our findings demonstrate that osteoclasts are capable of phagocytosing particles of a wide range of size, including particles of polymeric and metallic biomaterials found in periprosthetic tissues, and that after particle phagocytosis, they remain fully functional, hormone-responsive, bone-resorbing cells.

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Last Modified: 8 February 2006