Abstract: The Handbook of Materials for Medical Devices provides an in-depth review of the properties, processing, and selection of materials used in the environment of the human body - an environment that is surprisingly hostile and aggressive. Among the application areas described are orthopedics (hips, knees, and spinal and fracture fixation), cardiology (stents, heart valves, pacemakers), surgical instruments, and restorative dentistry. Materials discussed include metals and alloys, ceramics, glasses, and glass-ceramics, polymeric materials, composites, coatings, and adhesives and cements. The book is divided into three major sections. The first section provides an expansive overview of biomaterials and their use in medical devices. Charts and diagrams illustrate/list the many parts of the body that can be replaced by manmade materials. Case histories document some of the more common and successful medical device applications. Biocompatibility and mechanical requirements for implantable devices are also reviewed. The second section of the handbook deals with medical (nondental) applications. Stainless steels, cobalt-chromium alloys, titanium alloys, shape memory alloys, and tantalum are among the metallic materials described. Similar information is provided on nonmetallic materials, including new coatings that offer lubricity, biocompatibility, and antimicrobial action to device surfaces. Other coatings can be used to release drugs or make implanted devices more visible to imaging systems. The final section addresses biomaterials for dental applications. Emphasis is placed on corrosion and tribological behavior and corresponding test procedures to determine corrosion and wear resistance. Contents: Introduction: Overview of Biomaterials and Their use in Medical Devices; Physical and Mechanical Requirements for Medical Device Materials. Medical (Nondental) Applications: Metallic Materials; Corrosion of Metallic Implants and Prosthetic Devices; Failure Analysis of Metallic Orthopedic Implants; Ceramic Materials; Polymeric Materials; Adhesives and Cements; Coatings. Dental Applications: Biomaterials for Dental Applications; Tarnish and Corrosion of Dental Alloys; Friction and Wear of Dental Materials; Index.

Abstract: Highly porous poly(DL-lactic acid) (PDLLA) foams and Bioglass-filled PDLLA composite foams were characterized and evaluated in vitro as bone tissue engineering scaffolds. The hypothesis was that the combination of PDLLA with Bioglass in a porous structure would result in a bioresorbable and bioactive composite, capable of supporting osteoblast adhesion, spreading and viability. Composite and unfilled foams were incubated in simulated body fluid (SBF) at 37 degrees C to study the in vitro degradation of the polymer and to detect hydroxyapatite (HA) formation, which is a measure of the materials' in vitro bioactivity. HA was detected on all the composite samples after incubation in SBF for just 3 days. After 28 days immersion the foams filled with 40 wt % Bioglass developed a continuous layer of HA. The formation of HA for the 5 wt % Bioglass-filled foams was localized to the Bioglass particles. Cell culture studies using a commercially available (ECACC) human osteosarcoma cell line (MG-63) were conducted to assess the biocompatibility of the foams and cell attachment to the porous substrates. The osteoblast cell infiltration study showed that the cells were able to migrate through the porous network and colonize the deeper regions within the foam, indicating that the composition of the foams and the pore structures are able to support osteoblast attachment, spreading, and viability. Rapid formation of HA on the composites and the attachment of MG-63 cells within the porous network of the composite foams confirms the high in vitro bioactivity and biocompatibility of these materials and their potential to be used as scaffolds in bone tissue engineering and repair.

Abstract: A biodegradable composite scaffold was developed using beta-tricalcium phosphate (beta-TCP) with chitosan (CS) and gelatin (Gel) in the form of a hybrid polymer network (HPN) via co-crosslinking with glutaraldehyde. Various types of scaffolds were prepared by freezing and lyophilizing. These scaffolds were characterized by Fourier transform infrared, X-ray diffractometer, and scanning electron microscopy. The macroporous composite scaffolds exhibited different pore structures. Compressive properties were improved, especially compressive modulus from 3.9-10.9 MPa. Biocompatibility was evaluated subcutaneously on rabbits. A mild inflammatory response was observed over 12 weeks. The results suggest that the scaffolds can be utilized in nonloading bone regeneration.

Abstract: Iron-phosphate glass fibres based on the CaO-Na2O-Fe2O3-P2O5 system have been processed and characterised via thermal, XRPD, dissolution rates, diameter and biocompatibility studies. The compositions investigated were fixed at 50mol% P2O5, and the CaO content was varied between 30, 35 and 40mol%. The Fe2O3 was added in low amounts from 1-5mol%, substituting it for the Na2O mol%. The number of Tc (crystallisation temperature) peaks detected from the thermal analysis traces only showed correlation with XRPD analysis, for five out of the 15 compositions investigated. It has been suggested that either the crystalline phases had very similar Tc temperatures or that the other phase(s) were present in very small quantities. There was a good match seen with number of Tm (melting temperature) peaks picked up from the DTA traces, with the number of phases identified from XRPD analysis. The main phases identified from XRPD were NaCa(PO3)3, CaP2O6 and NaFeP2O7. Using network connectivity (NC), predictions on Qn species present within the compositions investigated were made. The predicted species (metaphosphates) matched with phases identified from XRPD analysis. A decrease in dissolution rates for the bulk glass and glass fibres was seen with an increase in CaO mol%, along with an increase in Fe2O3 mol%. An increase in fibre dissolution rates was seen with a decrease in diameter size. The biocompatibility studies were conducted using a conditionally immortal muscle precursor cell line derived from the H-2Kb-tsA58 immortomouse. It was found that iron-phosphate glass fibres containing 4-5mol% Fe2O3 was sufficient for cell attachment and differentiation. It was seen that myotubes formed along the axis of the fibres (which was indicative of differentiation). The biocompatibility of these compositions was attributed to the enhanced chemical durability of the glass fibres.

Abstract: Porous nano-hydroxyapatite/collagen/alginate (nHAC/Alginate) composite containing nHAC and Ca-crosslinked alginate is synthesized biomimetically. This composite shows a significant improvement in mechanical properties over nHAC material. Mechanical test results show that the compressive modulus and yield strength of this composite are in direct proportion to the percentage of Ca-crosslinked alginate in the composite. Primary biocompatibility experiments in vitro including fibroblasts and osteoblasts co-culture with nHAC/alginate composite indicated the high biocompatibility of this composite. Therefore the composite can be a promising candidate of scaffold material for bone tissue engineering.

Abstract: Biocompatibility relies essentially on surface phenomena, represented by cell-cell, cell-material and material (polymer)-protein interactions. An in vivo and in vitro experimental investigation was carried out on the biomaterials of two different classes with a good potential for in situ utilisation. Non-resorbable (Polypyrrole, Polyaniline, Polyimide) and resorbable (PLLA-PDXO-PLLA) materials for tissue engineering were studied for their overall tissue tolerance and cellular interactions. These non-resorbable polymers conceived for biosensor applications and implantable drug-delivery systems are intrinsically conductive. The PLLA-PDXO-PLLA triblock copolymer showed interesting tensile properties for bone and cartilage tissue engineering due to the presence of 1,5-dioxepan-2-one. In vitro and in vivo parallel studies showed an interesting correspondence: a) the cells in contact with the resorbable material that appeared to be capable of migratory-regenerative aspects in vitro exhibited good compatibility in vivo; whereas b) the non-resorbable materials, which are designed to remain in situ in vivo, were seen to have the potential to represent an adverse factor (inflammation, fibrotic reactions) that correlated with some aspects of cell behaviour in vitro.

Abstract: Polymeric hydrogels are used as wound dressing material since these materials show advantages such as pain relief, exudates absorption, barrier to microorganisms, permeability, and others. This article shows the results obtained in a study aiming to know the biological performance of different polymeric materials to be used in contact with skin: PVP hydrogels and acrylate adhesive. The biocompatibility was determined by in vitro assay of cytotoxicity and in vivo assay by using the contact test of irritability in rabbits. All the tested samples presented no toxicity and no dermal irritation.

Abstract: The specific aim of the present study was to investigate the biodegradation and biocompatibility characteristics of rosin, a natural film-forming polymer. Both in vitro as well as in vivo methods were used for assessment of the same. The in vitro degradation of rosin films was followed in pH 7.4 phosphate buffered saline at 37°C and in vivo by subdermal implantation in rats for up to 90 days. Initial biocompatibility was followed on postoperative days 7, 14, 21, and 28 by histological observations of the surrounding tissues around the implanted films. Poly (DL-lactic-co-glycolic acid) (PLGA) (50∶50) was used as reference material for biocompatibility. Rate and extent of degradation were followed in terms of dry film weight loss, molecular weight (MW) decline, and surface morphological changes. Although the rate of in vitro degradation was slow, rosin-free films showed complete degradation between 60 and 90 days following subdermal implantation in rats. The films degraded following different rates, in vitro and in vivo, but the mechanism followed was primarily bulk degradation. Rosin films demonstrated inflammatory reactions similar to PLGA, indicative of good biocompatibility. Good biocompatibility comparable to PLGA is demonstrated by the absence of necrosis or abscess formation in the surrounding tissues. The study provides valuable insight, which may lead to new applications of rosin in the field of drug delivery.

Abstract: The antifouling property and biocompatibility of a polyacrylonitrile-based copolymer membrane were improved by the immobilization of poly(ethylene glycol) (PEG) on the membrane surface. The studied membranes were fabricated from poly(acrylonitrile-co-maleic acid), in which the carboxyl groups could be conveniently conversed into anhydride and then esterified with poly(ethylene glycol). Chemical and morphological changes on the membrane surface were characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA), scanning electron microscopy (SEM), and sessile drop contact angle measurements (CA). It was found that the water contact angle of the membrane was reduced and the biocompatibility corresponding to platelets adhesion and protein adsorption was improved significantly with the immobilization of PEG chains on the membrane surface. Furthermore, the permeation behaviors of the base and modified membranes were investigated by bovine serum albumin (BSA) filtration experiments. M...

Abstract: In the last decades, the research on materials for bone regeneration has focused on materials that are degradable and capable of stimulating tissue regeneration. In this context, phosphate glasses offer an interesting alternative, given the wide range of solubility they present and their similarity with respect to the chemical composition of the bone mineral phase. In the current work, two different formulations of phosphate glasses in the system P(2)O(5)[bond]CaO[bond]Na(2)O[bond]TiO(2) are developed. The incorporation of TiO(2) into the glass network allows for better control of the glass dissolution rate. Although these glasses have been studied extensively from the physicochemical point of view, little is known about their biocompatibility. To evaluate the biological response to these materials, we have used a human skin fibroblast model. The cells were incubated in vitro following two different methods. The first was incubated in direct contact with the glasses and the second one, in the presence of their extracts. The effects of the materials on cell growth were determined by means of toxicity (WST assay), adhesion, and proliferation tests. The results showed that the in vitro behavior of soluble phosphate glasses is strongly affected by their solubility. On the other hand, the results showed that the cellular response is highly affected by the testing procedure.

Abstract: A novel system of body water elimination to be used for the treatment of edemas, based on superabsorbent cellulose derivatives able to absorb large amounts of water and water solutions, has been investigated. Hydrogels have been synthesized starting from water solutions of carboxymethylcellulose sodium salt and hydroxyethylcellulose, chemically crosslinked with divinylsulphone. Polyelectrolyte hydrogels displayed high sensitivity in sorption capacity to variations of the ionic strength and pH of the external solution, which is a key parameter for the application under investigation. Further, swelling properties have been modulated acting on the degree of crosslinking of the macromolecular network, and a direct method for the measurement of this parameter based on NMR solid-state analysis has been provided. The hydrogel biocompatibility has been studied in terms of its capacity either to induce nitric oxide and lactate dehydrogenase release by macrophages or influence their viability. The eventual release of toxic substances from the hydrogel was also investigated using Swiss 3T3 fibroblasts. The results obtained from the biocompatibility studies carried out in this work are consistent with the hypothesis that this gel may represent an alternative to diuretic therapies in those pathologic conditions in which edemas occur.

Abstract: “Compatibility” most broadly refers to the suitability of two distinct systems or classes of things to be mixed or taken together without unfavorable results. More specifically, the safety, effectiveness, and utility of medical nanorobotic devices will critically depend upon their biocompatibility with human organs, tissues, cells, and biochemical systems. Classical biocompatibility has often focused on the immunological and thrombogenic reactions of the body to foreign substances placed within it. In this Volume, we broaden the definition of nanomedical biocompatibility to include all of the mechanical, physiological, immunological, cytological, and biochemical responses of the human body to the introduction of medical nanodevices, whether “particulate” or “bulk” in form. That is, medical nanodevices may include large doses of independent micron-sized individual nanorobots, or alternatively may include macroscale nanoorgans (nanorobotic organs) assembled either as solid objects or built up from trillions of smaller artificial cells or docked nanorobots inside the body. We also discuss the effects on the nanorobot of being placed inside the human body.

Abstract: Biocompatibility and the Biomaterial-Tissue Interface. Tissue Engineering Equivalents. Delivery Systems. Emerging Concepts in Biomaterials. Index.

Abstract: The present invention is directed toward the renewable surface treatment of medical devices such as contact lenses and medical implants. In particular, the present invention is directed to a method of modifying the surface of a medical device to increase its biocompatibility or hydrophilicity by coating the device with a removable hydrophilic polymer by means of reaction between reactive functionalities on the hydrophilic polymer which functionalities are complementary to reactive functionalities on or near the surface of the medical device. The present invention is also directed to a contact lens or other medical device having such a surface coating.

Abstract: Titanium and its alloys are used worldwide in surgery. Dental implants, screws and plates, prostheses, and surgical instruments are made with titanium-based metals. The favorable characteristics that make this material desirable for implantation are (a) mechanical proprieties and (b) biocompatibility. The latter has been demonstrated by in vivo studies with animal models and clinical trials over a 40-year period. However, the exact effect of titanium on cells is still not well characterized. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of gene expression in a cell system. Several genes whose expression was significantly up- or downregulated in an osteoblast-like cell line (MG-63) on titanium were identified with the use of DNA microarrays containing 19,200 genes. The differentially expressed genes are associated with a broad range of functional activities, including apoptosis, vesicular transport, and structural function. It was also possible to detect some genes whose function is unknown. The data reported are, to the author's knowledge, the first genetic portrait of titanium-cell interaction. They may help to provide a better understanding of the molecular mechanisms of titanium biocompatibility and serve as a model for studying the biocompatibility of other materials.

Abstract: A biodegradable scaffold for skin-tissue engineering was designed using collagen and chitosan, which are common materials for biomedical application. The scaffolds containing different amounts of chitosan were prepared by mixing the collagen and chitosan solutions followed by removal of the solvent using a freeze-drying method. The cross-linking treatment of these scaffolds was performed using the dehydrothermal treatment (DHT) method or glutaraldehyde (GA) to increase their biostability. The effect of the chitosan concentration and the cross-linking methods on the morphology of these scaffolds was studied by SEM. The water retention and the biodegradability in vitro of various collagen-chitosan scaffolds were investigated. Finally the biocompatibility of the collagen-chitosan (10 wt% chitosan) scaffold treated with different cross-linking methods was evaluated using a in vivo animal test. A mild inflammatory reaction could be detected in the early stages, and GA treatment can decrease the inflammatory re...

Abstract: Improvement of the biocompatibility of alginate/poly-L-lysine/alginate microcapsules by the use of epimerized alginate as a coating

Abstract: Corrosion processes due to contact with the physiological environment should be avoided or minimized in orthopedic implants. Four metallic substrates frequently used as biomaterials: pure Ti, Ti-6Al-4V alloy, ASTM F138 stainless steel, and Co-Cr-Mo alloy, were coated with TiN using the physical vapor deposition (PVD) technique. These coatings have been screened by polarization curves in physiological solutions. TiN prepared by PVD is efficient as coating for stainless steel. On titanium and alloy there are no benefits concerning the corrosion resistance compared to the bare Ti-materials. TiN coatings have been screened according to ISO 10993 standard tests for biocompatibility and exhibited no cytotoxicity, dermal irritation, or acute systemic toxicity response.

Abstract: Grafting of encapsulated living cells has the potential to cure a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. A major factor in the biocompatibility of capsules is inadequate covering of the inflammatory poly-L-lysine (PLL) on the capsules' surface. In the present study, we investigate whether tissue responses against alginate-PLL capsules can be reduced by crosslinking the surface of the capsules with heparin or polyacrylic acid. Our transplant study in rats shows a tissue response composed of fibroblasts and macrophages on alginate-PLL-alginate and alginate-PLL-heparin capsules that was completely absent on alginate-PLL-polyacrylic acid capsules. Atomic force microscopy analyses of the capsules demonstrates that the improved biocompatibility of alginate-PLL-capsules by polyacrylic acid coating should not only be explained by a more adequate binding of PLL but also by the induction of a smoother surface. This study shows for the first time that biologic responses against capsules can be successfully deleted by chemically crosslinking biocompatible molecules on the surface of alginate-PLL capsules.

Abstract: Recently developed versatile biodegradable polymeric biomaterial offer new therapeutic options in numerous medical fields. Biocompatibility is a crucial requirement for the biomedical application of biomaterials, including the sterilization of these materials with the use of accepted protocols. Ethylene-oxide (EO) and low-temperature plasma (LTP) sterilization are frequently used low-temperature sterilization technologies for heat-sensitive materials. The agarose diffusion assay is a recommended cell-screening test to assess the cytotoxicity of biomaterials in vitro. The sensitivity of the agarose assay can be increased by using a modified computer-based image-analysis system. The influence of EO and LTP sterilization on the cytotoxicity of a versatile polymer system of shape-memory polymer networks based on oligo (epsilon-caprolactone) dimethacrylate and n-butyl acrylate was investigated. Statistically significant differences in the rate of cell lysis after EO and LTP sterilization of the polymer samples were detected by using this modified quantification system. The influence of the different sterilization techniques on the cytotoxicity of the polymeric material, as well as the clinical relevance of the described differences, are discussed.