Abstract: Biodegradable polymer/hydroxyapatite (HA) composites have potential application as bone graft substitutes. Thin films of polymer/HA composites were produced, and the initial attachment of primary human osteoblasts (HOBs) was assessed to investigate the biocompatibility of the materials. Poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLA) were used as matrix materials for two types of HA particles, 50-microm sintered and submicron nonsintered. Using ESEM, cell morphology on the surfaces of samples was investigated after 90 min, 4 h, and 24 h of cell culture. Cell activity and viability were assessed after 24 h of cell culture using Alamar blue and DNA assays. Surface morphology of the polymer/HA composites and HA exposure were investigated using ESEM and EDXA, respectively. ESEM enabled investigation of both cell and material surface morphology in the hydrated condition. Combined with EDXA it permitted chemical and visual examination of the composite. Differences in HA exposure were observed on the different composite surfaces that affected the morphology of attached cells. In the first 4 h of cell culture, the cells were spread to a higher degree on exposed HA regions of the composites and on PLA than they were on PCL. After 24 h the cells were spread equally on all the samples. The cell activity after 24 h was significantly higher on the polymer/HA composites than on the polymer films. There was no significant difference in the activity of the cells on the various composite materials. However, cells on PCL showed higher activity compared to those on PLA. A polymer surface exhibiting "point exposure" of HA appeared to provide a novel and favorable substrate for primary cell attachment. The cell morphology and activity results indicate a favorable cell/material interaction and suggest that PLA and PCL and their composites with HA may be candidate materials for the reconstruction of bony tissue. Further investigations regarding long-term biomaterial/cell interactions and the effects of acidic degradation products from the biodegradable polymers are required to confirm their utility.

Abstract: Disclosed are medical prosthetic device or medical implants which exhibit improved biocompatibility. The devices or implants include a metal material, e.g., titanium, in which the metal surfaces are coated with a corresponding hydride material that contains one or more biomolecule substance. The biomolecule substance may contain one or more biologically active molecules, e.g., bio-adhesives, biopolymers, blood proteins, enzymes, extracellular matrix proteins, extracellular matrix biomolecules, growth factors and hormones, peptide hormones, deoxyribonucleic acids, ribonucleic acids, receptors, inhibitors, drugs, biologically active anions and cations; vitamins; adenosine monophosphate (AMP), adenosine diphosphate (ADP) or adenosine triphosphate (ATP), marker biomolecules, amino acids, fatty acids, nucleotides (RNA and DNA bases), or sugars.

Abstract: ▪ Abstract This review summarizes recent advances and future research trends in the field of phospholipid-based biomaterials. Lipids play an important role in biomineralization and countless other biological processes, and they are receiving increasing attention for the synthesis of new biomimetic biomaterials. Several emerging strategies in biomaterials research take advantage of phospholipids to compartmentalize and/or template chemical reactions via self-assembled structures such as liposomes and tubules. Still others exploit the inherent biocompatibility of phospholipids and phospholipid-mimetic materials for use as novel tissue-contacting biomaterials that mimic biological membranes. In the future, phospholipid-based materials may be increasingly utilized as tools for the manipulation of cell and tissue responses to biomaterials, for controlled drug release, for reconstructive surgery, and as tissue-engineered constructs.

Abstract: This study investigated the basic biocompatibility aspects of two types of polypyrrole (PPy)-coated polyester fabrics for possible use as vascular prostheses. These PPy-coated fabrics, PPy-Phos and PPy-Plas, were sterilized with ethylene oxide (EO) and the following characterizations were performed: surface morphology by scanning electron microscope, EO residuals analysis by the headspace method, acute systemic toxicity in the mouse model, hemolysis, blood coagulation time, viability and proliferation of endothelial cells measured with the WST-1 method, and activation of polymorphonuclear (PMN) cells indicated by the specific expression of interleukin 8 mRNA measured by reverse transcription polymerase chain reaction. Virgin polyester fabrics, expanded poly(tetrafluoroethylene) (ePTFE), and medical-grade Bionate 80A poly(carbonate urethane) were used as references in the cell culture experiments. The PPy-coated fabrics revealed different surface morphologies by showing more PPy lamina and clusters on the PPy-Plas. Neither of the PPy-coated fabrics had an adverse effect on hemolysis and coagulation time, and they did not cause any acute systemic toxicity. The EO residual level was as low as 5 ppm or less, which is considered quite acceptable. Although exhibiting a relatively low initial cell adhesion at 24 h, the two PPy-coated samples showed no cytotoxicity at 72 and 168 h. Bionate 80A and ePTFE recorded cytotoxicity at 72 and 168 h, respectively. The virgin fabrics also demonstrated a decrease of viable cells at 72 h that was not significant. The activation of PMN cells induced by both PPy-coated fabrics, the ePTFE, and the negative control was significantly lower than that induced by their respective tumor necrosis factor-alpha controls. These results therefore highlighted the potential of PPy-coated fabrics for use as cardiovascular prostheses. It was suggested that cell adhesion moieties should be incorporated into the PPy/fabric composite to increase cell adhesion and subsequent cell proliferation.

Abstract: V ions exhibit cytotoxicity in a culture medium from concentrations of ≧0.2 mg/L. Ti, Zr, Nb and Ta are biocompatible elements. A new Ti–15Zr–4Nb–4Ta alloy for medical implants is being developed. Its microstructure, mechanical properties, corrosion resistance and corrosion fatigue properties in a physiological saline solution, biocompatibility with cultured cells, new bone tissue response through rat tibia implantation and surface modification are discussed. Medical applications will be also addressed.

Abstract: Commercially pure titanium (cpTi), titanium alloys, and steel are often used for dental and orthopedic implants. In these applications titanium is considered the "gold standard." However, tissue reactions around titanium implants and the changing trend to leave orthopedic devices in the body have led to a new examination of the preferred material. This in vitro study tested the behavior of osteoblasts on cpTi, Ti-6Al-7Nb, and stainless steel with surface designs similar to clinical implants. After surface characterization by scanning electron microscopy and profilometry, cell proliferation and the differentiation parameters of alkaline phosphatase (ALP) activity and osteocalcin were measured. For all materials tested, the growth curves showed a similar kinetic. On Ti-6Al-7Nb, ALP activity was significantly lower when compared with steel, and cpTi and did not change over the time. ALP activity increased moderately on steel and cpTi. Osteocalcin levels were higher on both titanium materials than on steel. Based on undisturbed cell growth and the relatively high alkaline phosphatase and osteocalcin levels, we suggest that cpTi provides the best biocompatibility with regard to proliferation, in addition to more reliable early and late differentiation markers of human osteoblasts in vitro.

Abstract: The aim of this study was to investigate the swelling properties and the biocompatibility of a novel tissue expander material. The self-inflating material is a hydrogel consisting of a modified copolymer of methylmethacrylate and N-vinyl-2-pyrrolidone, which takes up water by osmosis. To increase the swelling volume, the primarily neutral gel material was modified by converting it into an ionized gel. To study the swelling and pressure behavior of the material, the anhydrous gel cylinders were equilibrated in distilled water, saline, and sugar solutions. The biocompatibility was investigated in cell culture. We tested the hydrogel eluate after swelling for cytotoxicity and mutagenicity using the cell lines MRC-5 and P3X63 Ag8 653 (Ag8). Furthermore, particles of the material were added to cell cultures to induce foreign body reactions and to verify its influence on monocyte differentiation. The material has a swelling capacity (Q = maximum swelling volume/anhydrous volume) of 5 to 50 depending on the degree of ionization of the polymer network. In this study, two polymer modifications with a swelling equilibrium of Q = 11.1 and 30 in water were tested. The swelling ratio also depends on concentration and ion content of the equilibration medium. The highest swelling capacity was found in water, the lowest in Ringer's solution. The swelling of the anhydrous material with the swelling capacity of Q = 11.1 fits best the average purpose of material properties for tissue expansion and generates a maximal hydrostatic pressure of approximately 235 mmHg. Effects on cell proliferation were detected only at the highest eluate concentration tested (i.e., eluate: culture medium = 1:1), which was far beyond physiological values, whereas mutagenicity was absent. Monocytes neither migrated nor tightly attached to the hydrogel. They neither phagocytose the material nor did they show any sign of a foreign body reaction, e.g., formation of multinucleated giant cells or monocyte proliferation. In the presence of hydrogel material, the differentiation processes of monocytes to macrophages or dendritic cells, respectively, were found to be undisturbed. From these results, we conclude that there is a high biocompatibility of the expander material, which may be a favorable and interesting candidate for further clinical applications.

Abstract: An implant device is provided which incorporates a retinoid for improving the biocompatibility of the device in tissue. The device may be bioerodible for the purpose of systemically or locally releasing a therapeutic agent in tissue or it may be a permanent implant which includes a surface treated with a retinoid for increasing the biocompatibility thereof.

Abstract: The widespread and successful application of titanium (Ti) in medical implants is unquestionable. If, each year, Ti is used with good outcomes in hundreds of thousands of clinical implants, surely it must be biocompatible? This supposition will be examined in light of the definition of biocompatibility, ideas on the foreign body reaction and new developments in surface modification.

Abstract: Background: Current literature shows that calcium sulfate can be used in guided tissue regeneration. Its biocompatibility and resorbability give it significant advantages in the treatment of periodontal and endodontic defects. Clinically guided tissue regeneration procedures have demonstrated significant positive clinical change, beyond that achieved with debridement alone, in treating intraosseous defects. The aim of the present investigation was to evaluate the clinical results obtained with autologous bone plus calcium sulfate, and to compare them with the results obtained using autologous bone plus membrane. Methods: A total of 12 patients were treated in the present investigation. A split-mouth design was utilized. Twelve 3-wall periodontal defects were treated with calcium sulfate plus autologous bone graft (test) and compared with 12 contra-lateral defects treated with a bioabsorbable membrane plus autologous bone graft (control). Before the surgical procedure, patients were instructed about oral h...

Abstract: Angiogenesis is essential in wound healing and a common feature in chronic inflammation which is crucially involved in the biological response to biomaterials. A useful system to evaluate the angiogenic activity and the inflammatory potency of various agents is the chorioallantoic membrane (CAM) of the chick embryo. Here we examined its response to different biomaterials. Smooth materials such as PVC or the polyurethane Tecoflex either unmodified or modified by an OH- or N(CH(3))(3)(+)-end group (HEMA or MAPTAC) inhibited angiogenesis and did not induce the formation of granulation tissue. The anti-angiogenic effects of PVC, Tecoflex and its HEMA modification, however, were only seen at an early stage of development. In contrast, the MAPTAC modified Tecoflex inhibited angiogenesis over the whole time. Rough materials, e.g. filter paper or a collagen/elastin membrane, stimulated angiogenesis and induced the formation of inflammatory tissue. Histological analysis revealed that the filter material was homogeneously populated with cells consisiting mainly of macrophages, fibroblasts and endothelial cells. The collagen/elastin membrane was only partially infiltrated with cells. Among those also clusters of granulocytes were present pointing to an acute inflammatory process. These data show that the angiogenic activity and inflammatory response of biomaterials strongly depend on the chemical composition and the physical structure of the material. The CAM assay appears to be a useful tool for studying biocompatibility.

Abstract: The extracellular matrix molecular collagen is the one of the most widely utilized scaffolding materials in tissue engineering. However, obtaining uniform bioactive collagen films in the nanoscale range and precisely controlling the physical and chemical properties of these biological films is still a challenge for biomedical engineering. Layer-by-layer assembly, i.e., sequential adsorption of oppositely charged macromolecular species, is a powerful new film preparation technique that can be applied to the design of versatile biomaterials, with well-controlled interfacial, mechanical and biological functions. To demonstrate the feasibility of biomaterial design by means of layer-by-layer assembly, type-I collagen thin films were prepared by using this technique with poly(styrene) sulfonate as a partner polyelectrolyte. The gradual build-up of the collagen films was confirmed by UV-vis spectroscopy and ellipsometry, while their surface morphology was assessed by atomic force microscopy. The thickness of the collagen layers can be changed by increasing the number of bilayers adsorbed with an increment of 13 nm. It was found that the layer-by-layer assembled collagen scaffolds can support the attachment and growth of C2C12 myoblast cells and PC12 pheochromocytoma cells. Accurate thickness control and compatibility with nerve cell precursors indicate the utility of layer-by-layer assembled films in neuroprosthesis.

Abstract: We make a subtrate biocompatible by contacting it with a starting material and initiating alternating charge layer electrostatic self-assembly to form a thin film. Starting materials may be poly(vinylpyrrolidone), poly{bis-(carboxylatophenoxy)phosphazene}, poly(methacrylic acid), poly(l)-lysine, poly(ethylene glycol), poly(D-glucosamine), poly(l-glutamic acid), poly(diallyldimethylamine), poly(ethylenimine), hydroxy fullerene, long-sidechain fullerene, or other polymers that participate in electrostatic self-assembly. The thin film fabrication advantageously may be at room temperature. A biocompatible thin film that is uniform and homogeneous can be provided. Optionally, ZrO2, Al2O3 or TiO2 nanoclusters also may be used in the film assembly. The film may be used in a drug delivery device or a medical device. The film may be used for tissue engineering. We also provide a biocompatible composition in which are present a plurality of layers electrostatically self-assembled from at least a polymer or fullerene asmentioned. The substrate is not particulary limited, and may be quartz, glass, plastic, metal or ceramic, a material for a bone implant, bioactive glass, polyester or other polymers, plastic or rubber tubing, bandaging material, composite material, insulator material, semi-conductor material, an artificial hip, a pacemaker, a catheter, a stent or other substrates.

Abstract: The semi-IPN hydrogel membranes of polyvinyl pyrrolidone (PVP) and β-chitosan were synthesized by crosslinking β-chitosan with glutaraldehyde. Hydrogel membranes were characterized by spectroscopic, swelling, thermal and mechanical properties. The in vitro biocompatibility of hydrogel membranes was studied by haemorheological method. These hydrogels have water contents in the range of 60–70% with a high fraction contributed by free water (> 45%). The gel composition, amount of cross-linking agent and swelling temperature plays an important role in swelling kinetics of these semi-IPN membranes. Melting temperature (T m ) of membranes increased with a decrease in endothermic peak with increasing β-chitosan content. The tensile strength of membranes in the dry state was found to be high (29–43 MPa) and it increased with increasing β-chitosan content. The in vitro haemorheological studies indicated the biocompatible nature of membranes with no significant changes in whole blood and plasma viscosity and red blood cell rigidity.

Abstract: Phosphorylcholine-based polymers have been used commercially to improve the biocompatibility of coronary stents. In this study, one particular polymer is assessed for its suitability as a drug delivery vehicle. Membranes of the material are characterized in terms of water content and molecular weight cut-off, and the presence of hydrophilic and hydrophobic domains investigated by use of the hydrophobic probe pyrene. The in vitro loading and elution of a variety of drugs was assessed using stents coated with the polymer. The rate of a drug's release was shown not to be simply a function of its water solubility, but rather more closely related to the drug oil/water partition coefficient. This finding was explained in terms of the more hydrophobic drugs partitioning into, and interacting with, the hydrophobic domains of the polymer coating. The suitability of the coated stent as a drug delivery vehicle was assessed in vivo using a radiolabeled analog of one of the more rapidly eluting drugs, angiopeptin. Autoradiography showed that the drug was released locally to the wall of the stented artery, and could be detected up to 28 days after implantation.

Abstract: As-received and heat-treated Ti40Ta and Ti50Ta alloys were evaluated to determine their corrosion as well as mechanical performances and compared to Ti6A14V, a common material utilized for orthopedic (surgical) implants. Anodic potentiodynamic tests performed in PlasmalyteTM showed that all samples, except for the Ti50Ta specimen aged at 400 °C for 3 h gave a curve similar to that of Ti6A14V. Optical and TEM microscopy was performed to determine as-received and heat-treated microstructures. As-received materials showed an α precipitate in an α+β and martensite matrix. Samples that were aged at 400 °C increased in the density and the length of the α precipitate. Vickers hardness measurements were performed to get an approximation of the tensile strengths. Aged Ti40Ta and Ti50Ta specimens produced the highest tensile values when compared to the Ti6A14V material, representing a 31% and 56% increase for the 3 h samples and an 18% and 58% increase for the 10 h samples. Of all the materials studied the Ti50Ta specimen aged for 10 h exhibited the best biocompatibility showing excellent corrosion resistance combined with the highest tensile strength (1089 MPa and 58% harder/stronger than Ti6A14V). © 2001 Kluwer Academic Publishers

Abstract: Object. Stereotactically guided implantation of biodegradable microspheres is a promising strategy for delivery of neurotrophic factors in a precise and spatially defined brain area. The goal in this study was to show the biocompatibility of poly(D,L,lactide-co-glycolide) microspheres with brain tissue at the ultrastructural level and to analyze the three-dimensional (3D) ultrastructure after intrastriatal implantation of these microparticles. Methods. Scanning and transmission electron microscopy were used to study the microspheres and their environment after implantation in an inert material (gelatin) and in the rat striatum. Observations were made at different time periods, ranging from 24 hours to 2 months postimplantation. Conclusions. The progressive degradation of the microspheres, with vacuolization, deformation, and shrinkage, was well visualized. This degradation was identical in microspheres implanted in the inert material and in the rat brain tissue, independent of the presence of macrophages. The studies preformed in the striatum permitted the authors to demonstrate the structural integrity of axons in contact with microspheres, confirming the biocompatibility of the polymer. Furthermore, scanning electron microscopy showed the preservation of the 3D ultrastructure of the striatum around the microparticles. These microparticles, which can be stereotactically implanted in functional areas of the brain and can release neurotrophic factors, could represent, for some indications, an alternative to gene therapy.

Abstract: The barrier membranes for guided tissue regeneration (GTR) to treat bone defects have to satisfy the criteria of biocompatibility, cell-occlusiveness, space-making, tissue integration and clinical manageability. In this study a system constituted of a poly(L-lactide) acid (PLLA) asymmetric membrane combined with an alginate film was prepared. The PLLA membrane functions to both support the alginate film and separate the soft tissue; the alginate film is intended to act as potential vehicle for the growth factors to promote osteogenesis. The structural, morphological, and mechanical properties of the bilamellar membrane and its stability in culture medium were evaluated. Moreover, the feasibility of using the alginate membranes as controlled-release delivery vehicles of TGF-beta was monitored. Finally, the bacterial adhesion and permeability of Streptococcus mutans, selected for the high adhesive affinity, were monitored. The results showed that the surfaces of the alginate side, to be used in contact with the bone defect, were rougher than PLLA ones. When in contact with complete culture medium, the PLLA-alginate membrane retained its mechanical and structural properties for more than 100 days. Then, the degradation processes occurred but the membrane continued to be stable and manageable for 6 months. Growth factors such as TGF-beta can be incorporated into alginate membranes functioning as drug delivery vehicle, and retain the biological activity when tested in an in vitro model system. The obtained membrane acted as a barrier to the passage of S. mutans bacteria and showed to promote a lower bacterial adhesion with respect to commercial GTR membranes.