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Biomaterial-host interactions: consequences, determined by implant retrieval analysis
Kaplan, S. S. (1994), Med Prog Technol 20(3-4): 209-30.
Abstract: Prosthetic biomaterials have had a profound impact on reconstructive surgery but complete biocompatability remains illusive. This review considers the retrieval analysis of four common prosthetic structures: the hip, the knee, heart valves, and blood vessels. We show that despite a fine record of early success, deterioration due to mechanical failure or deleterious host responses to the implant may compromise long term function. The eventual retrieval and detailed analysis of implanted structures provides an invaluable opportunity to determine the characteristics of implant success or failure and to provoke the development of still better materials.

Biomaterial-induced alterations of human neutrophils under fluid shear stress: scanning electron microscopical study in vitro
Tomczok, J., W. Sliwa-Tomczok, et al. (1996), Biomaterials 17(14): 1359-67.
Abstract: Morphological changes of human polymorphonuclear neutrophils (PMN) adhering to hydrophilic (glass) and hydrophobic (FEP-Teflon, polyethylene, polypropylene) surfaces were studied in a parallel-plate flow chamber at the light and scanning electron microscopical levels. The PMN were exposed to a shear stress of 0.19 Pa (1.9 dynes cm-2) or were allowed to adhere without the stress component (static control) during 30 min for all four biomaterials. Observation by light microscopy was performed in situ in the flow chamber at 1, 5, 10, 15, 20, 25 and 30 min. The total number of adherent cells as a function of time and the activation status of the population on the basis of morphological criteria were determined. On the hydrophilic material adhesion of activated PMN was significantly higher (P < 0.05) than on the more hydrophobic surfaces. This effect was most pronounced for the adhesion of neutrophils to glass and polypropylene (PP). Polyethylene (PE) showed only minor adhesion rates. Scanning electron microscopy revealed details of cell shape changes and permitted a more precise classification of populations of neutrophils based on distinctive shapes. As PMN were exposed to shear stress on glass, the majority of cells exhibited surface veils, ridges and ruffles, suggesting a high level of cell migration. In this case, on polymeric surfaces the presence of filopodial networks (FEP-Teflon) and ameoboid cell shapes (PP and PE) was noted. The results suggest that a low shear stress, as well as various chemical and physical properties of biomaterial surfaces, are together responsible for differentiation of PMN populations on solid substrata.

Biomaterial-induced alterations of neutrophil superoxide production
Kaplan, S. S., R. E. Basford, et al. (1992), J Biomed Mater Res 26(8): 1039-51.
Abstract: Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

Biomaterial-induced dysfunction in the capacity of rabbit alveolar macrophages to kill Staphylococcus epidermidis RP12
Giridhar, G., Q. N. Myrvik, et al. (1995), J Biomed Mater Res 29(10): 1179-83.
Abstract: The effect of poly(methyl methacrylate) (PMMA), titanium alloy, and silicone discs on the capacity of rabbit alveolar macrophages (AM) to kill RP12 strain of Staphylococcus epidermidis (RP12) was studied in vitro. When freshly harvested AM were preincubated with PMMA discs for 3 h and subsequently assayed for RP12 killing, there was no change in the RP12 killing capacity of AM. However, when AM were incubated with PMMA discs for 6 or 18 h at 37 degrees C in 5% CO2, the RP12 killing capacity of AM was reduced to 15% and 4%, respectively. Preincubation of AM with titanium alloy for 6 h reduced RP12 killing capacity of AM to 30%, and to 21% in 18-h incubation. Silicone discs did not affect the RP12 killing by AM at 6 h of preincubation, but reduced RP12 killing (35%) by AM when preincubated for 18 h. Preincubation of AM with PMMA discs for 3 or 6 h did not affect the level of PMA-elicited oxidative burst of AM as measured by a luminol-enhanced chemiluminescent assay. Superoxide dismutase, which eliminated the oxidative burst of AM by 90%, did not affect the RP12 killing by AM.

Biomaterial-induced macrophage activation and monokine release
Zenni, G. C., J. Ellinger, et al. (1994), J Invest Surg 7(2): 135-41.
Abstract: This study quantifies macrophage acid phosphatase release as a marker of cell activation when cultured with or without biomaterials. Peritoneal macrophages were harvested from six New Zealand White rabbits and cultured in minimum essential media with 10% equine serum. After cell identification by morphology, nonspecific esterase, and RAM 11 immunoperoxidase, cells were passaged twice, and second-passage macrophages were seeded in 96-well plates (5,000 cells/well) and grown to confluence. After collection of day zero media, circular disks of polyglactin 910 and two types of commercially available polyethylene terephthalate with different construction and sterilization characteristics were placed on the cell monolayer. Controls without biomaterials were also established. Media was collected and pooled for each group and time point beginning on day 2 and continuing every other day for 22 days. Conditioned media were quantitatively assayed for acid phosphatase colorimetrically at 402 nm using p-nitrophenylphosphate as the substrate. Acid phosphatase activity increased progressively at late time points for each group but no difference was noted between groups at any time point. These data show that the activation of cultured macrophages with time is not altered differentially by the presence of biomaterials. The previously demonstrated monokine release following biomaterial exposure is therefore a specific event and not simply part of the generalized activation phenomenon.

Biomaterial-induced sarcoma: A novel model to study preneoplastic change
Kirkpatrick, C. J., A. Alves, et al. (2000), Am J Pathol 156(4): 1455-67.
Abstract: In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.

Biomaterial-microvasculature interaction on polymers after implantation in mice
Binzen, E., A. Lendlein, et al. (2004), Clin Hemorheol Microcirc 30(3-4): 283-8.
Abstract: Biomaterial research is expected to forward new materials to be used as, e.g., implant materials or as scaffolds for tissue engineering. It is central for such a scaffold material to create the track on which those cells can inhabitate the scaffold needed to rebuild functional tissue substitutes. For the biointegration of the implant with the native cellular tissue this must be able to grow on the material surface. For the elimination of the degradation products and the adeqaute transport of nutrients/gases within the newly formed tissue the angiogenesis of new blood vessels is thought to play an important role. In the present study, a new biomaterial, a non-porous polymeric AB-network based on oligo (epsilon-hydroxycaproat) and oligobutylacrylat, was implanted in animals. Male NMRI mice were implanted subcutaneously for one week to nine weeks. Immediately after the explantation, the probes were examined histologically. Already one week after implantation, there was a strong tissue-integration of the polymer. Importantly, blood vessels appeared at the polymer surface. At nine weeks after implantation the tissue integration was stronger than after one week and blood vessels were still observed in the periimplant tissue. The mechanism of the early integration of the polymer is not clear. The relationship between the new periimplant vessels and the integration of the polymer has to be studied.

Biomaterial-microvasculature interactions
Sieminski, A. L. and K. J. Gooch (2000), Biomaterials 21(22): 2232-41.
Abstract: The utility of implanted sensors, drug-delivery systems, immunoisolation devices, engineered cells, and engineered tissues can be limited by inadequate transport to and from the circulation. As the primary function of the microvasculature is to facilitate transport between the circulation and the surrounding tissue, interactions between biomaterials and the microvasculature have been explored to understand the mechanisms controlling transport to implanted objects and ultimately improve it. This review surveys work on biomaterial-microvasculature interactions with a focus on the use of biomaterials to regulate the structure and function of the microvasculature. Several applications in which biomaterial-microvasculature interactions play a crucial role are briefly presented. These applications provide motivation and framework for a more in-depth discussion of general principles that appear to govern biomaterial-microvasculature interactions (i.e., the microarchitecture and physio-chemical properties of a biomaterial as well as the local biochemical environment).

Biomaterial-neutrophil interactions: dysregulation of oxidative functions of fresh neutrophils induced by prior neutrophil-biomaterial interaction
Kaplan, S. S., R. E. Basford, et al. (1996), J Biomed Mater Res 30(1): 67-75.
Abstract: Biomaterial-associated infection results in increased morbidity and mortality, and may occur because of nonproductive premature activation of neutrophils resulting in impaired phagocyte function at the biomaterial surface in the event of bacterial challenge. To further explore the effects of this premature activation, we evaluated the supernatants of biomaterial associated neutrophils to determine whether soluble mediators were released, and the likely role of these mediators. We show that these supernatants contain a chemoattractant and thereby induce chemotaxis by fresh neutrophils. No evidence of enhanced oxidative free radical production by either unstimulated neutrophils or a primed response to other mediators occurs when neutrophils were incubated with these supernatants. We also examined the effect of adding fresh neutrophils to a biomaterial surface containing a previous inoculum of neutrophils, and observed that the fresh cells did not become stimulated to release reactive oxygen intermediates (ROI) and also exhibited impaired killing of staphylococci. These studies suggest that not only does the biomaterial surface activate the initial wave of neutrophils but that subsequent waves of neutrophils exhibit an impaired host-defense function. These results are consistent with the known impairment of host defense in the presence of biomaterials, and provide evidence for a long-term down-regulation of neutrophil function at biomaterial surfaces.

Biomaterials
Hench, L. L. (1980), Science 208(4446): 826-31.

Biomaterials Access Assurance Act of 1998: a legislative success
Melnick, A. (1999), Pacing Clin Electrophysiol 22(9): 1402-3.

Biomaterials and availability
Galletti, P. (1997), Asaio J 43(6): 882-3.

Biomaterials and biocompatibility
Williams, D. F. (1976), Med Prog Technol 4(1-2): 31-42.
Abstract: This review attempts to assess the present status of biomaterials, especially in relation to their interaction with tissue. The terms biomaterial and biocompatibility are defined and both the present areas of clinical application and the requirements of biomaterials for these applications discussed. The types of biomaterials in clinical use and those under development are briefly described. Problems associated with implant functionality are covered, dealing with fatigue, wear and membrane permeability. Of more importance are the problems relating to biocompatibility and metallic corrosion, polymer and ceramic degradation, local tissue changes, systemic effects, infection, implant loosening, blood compatibility and the assessment of biocompatibility.

Biomaterials and biocompatibility in hemodialysis
Klinkmann, H., D. Falkenhagen, et al. (1987), Contrib Nephrol 55: 231-49.

Biomaterials and biomechanics in dental implant design
Brunski, J. B. (1988), Int J Oral Maxillofac Implants 3(2): 85-97.

Biomaterials and biomechanics of oral and maxillofacial implants: current status and future developments
Brunski, J. B., D. A. Puleo, et al. (2000), Int J Oral Maxillofac Implants 15(1): 15-46.
Abstract: Research in biomaterials and biomechanics has fueled a large part of the significant revolution associated with osseointegrated implants. Additional key areas that may become even more important--such as guided tissue regeneration, growth factors, and tissue engineering--could not be included in this review because of space limitations. All of this work will no doubt continue unabated; indeed, it is probably even accelerating as more clinical applications are found for implant technology and related therapies. An excellent overall summary of oral biology and dental implants recently appeared in a dedicated issue of Advances in Dental Research. Many advances have been made in the understanding of events at the interface between bone and implants and in developing methods for controlling these events. However, several important questions still remain. What is the relationship between tissue structure, matrix composition, and biomechanical properties of the interface? Do surface modifications alter the interfacial tissue structure and composition and the rate at which it forms? If surface modifications change the initial interface structure and composition, are these changes retained? Do surface modifications enhance biomechanical properties of the interface? As current understanding of the bone-implant interface progresses, so will development of proactive implants that can help promote desired outcomes. However, in the midst of the excitement born out of this activity, it is necessary to remember that the needs of the patient must remain paramount. It is also worth noting another as-yet unsatisfied need. With all of the new developments, continuing education of clinicians in the expert use of all of these research advances is needed. For example, in the area of biomechanical treatment planning, there are still no well-accepted biomaterials/biomechanics "building codes" that can be passed on to clinicians. Also, there are no readily available treatment-planning tools that clinicians can use to explore "what-if" scenarios and other design calculations of the sort done in modern engineering. No doubt such approaches could be developed based on materials already in the literature, but unfortunately much of what is done now by clinicians remains empirical. A worthwhile task for the future is to find ways to more effectively deliver products of research into the hands of clinicians.

Biomaterials and biomedical devices
Hanker, J. S. and B. L. Giammara (1988), Science 242(4880): 885-92.
Abstract: This review discusses the factors important in the incorporation or integration of biomaterials and devices by tissue. Methods for surface modification and surface-sensitive techniques for analysis are cited. In vitro methods to evaluate the biocompatibility or efficacy of certain biomaterials and devices are presented. Present and future directions in neural prostheses, cardiovascular materials, blood or bone substitutes, controlled drug delivery, orthopedic prostheses, dental materials, artificial organs, plasma- and cytapheresis, and dialysis are discussed.

Biomaterials and biotechnology. The union of these technologies promises solutions to recalcitrant problems
Hellman, K. B., G. L. Picciolo, et al. (1993), Biotechnology (N Y) 11(10): 1179-80.

Biomaterials and bone mechanotransduction
Sikavitsas, V. I., J. S. Temenoff, et al. (2001), Biomaterials 22(19): 2581-93.
Abstract: Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

Biomaterials and cardiovascular devices
Macnair, R., M. J. Underwood, et al. (1998), Proc Inst Mech Eng [H] 212(6): 465-71.
Abstract: In the field of cardiovascular surgery there is presently a lack of biomaterials possessing essential characteristics of the native tissue or organ which is to be replaced. This paper describes various biomaterials that have been introduced into the circulatory system and the complex reactions that subsequently occur. The risk of infection is also discussed as well as prevention and treatment regimes that can be used. Examples of future biomaterial development are outlined in an attempt to achieve biocompatibility.


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