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Semi-interpenetrating polymer networks composed of biocompatible phospholipid polymer and segmented polyurethane.

2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers, which have excellent biocompatibility, have been receiving increasing attention in biomedical and bioengineering fields; however, the mechanical strength of the hydrated MPC polymers is not sufficient for use in these fields as a bulk material. Therefore, we hypothesized that a novel material might be realized by reinforcing the MPC polymer network with segmented polyurethane (SPU). Semi-interpenetrating polymer networks (IPNs) composed of crosslinked MPC polymer and SPU were prepared. The mechanical properties of the IPN membrane were significantly improved compared with those of the MPC polymer membrane. Three-dimensional polymer networks of the MPC polymer in the IPNs were observed after solvent extraction of SPU. An X-ray photoelectron spectrum analysis revealed that the MPC units were exposed on the IPN surface. When the IPN was alternately soaked in water and ethanol, the swelling ratio was found to be completely reversible and no disintegration of the network structure was observed. The permeation coefficient of 1, 4-di(2-hydroxyethoxy)benzene through the IPN membrane was 1.11 x 10(-7) cm(-2)s(-1). The amount of adsorbed protein and the number of adherent platelets on the IPN membrane were effectively reduced compared with those on SPU. We concluded that IPNs composed of the MPC polymer and SPU are a new bulk biomaterial, which possesses both blood compatibility and good mechanical properties.

Absorption↗

Improved calcification resistance and biocompatibility of tissue patch grafted with sulfonated PEO or heparin after glutaraldehyde fixation.

A novel chemical modification of biological tissues was developed aimed at improving biocompatibility and calcification resistance. This method involved the additional grafting of sulfonated PEO (PEO-SO(3)) or heparin after conventional glutaraldehyde (GA) fixation of bovine pericardium (BP). The amino groups of PEO-SO(3) or heparin were utilized to react to the GA residues to block them. The PEO-SO(3) or heparin grafted tissues demonstrated a slightly higher shrinkage temperature and tensile strength, but greater resistance to collagenase digestion, than GA treated ones. These results suggest that modified tissues have improved durability due to the grafting and filling effect of PEO-SO(3) or heparin in addition to the GA cross-linking. At the direct contact cytotoxicity test in vitro, PEO-SO(3) or heparin grafted tissue was shown to be nontoxic, while relatively significant cytotoxicity was observed for the GA treated tissues, possibly due to the release of GA. From the in vivo calcification study, calcium contents deposited on the modified tissues were much less than those on GA treated tissues. Such a decreased calcification might be explained by the decrease of residual GA groups during the additional treatment, and the space-filling effect and the nonadhesive property and/or the blood compatibility of PEO-SO(3) or heparin grafted covalently. The newly modified tissue patch was observed to show improved pathological assessibility including less inflammation and tissue reactions. This simple modification method may be useful for calcification-resistant and blood-compatible tissue patches for cardiovascular implants.

Animals↗

In vitro and in vivo investigations into the biocompatibility of diamond-like carbon (DLC) coatings for orthopedic applications.

Diamond-like carbon (DLC) shows great promise as a durable, wear- and corrosion-resistant coating for biomedical implants. The effects of DLC coatings on the musculoskeletal system have not been investigated in detail. In this study, DLC coatings were deposited on polystyrene 24-well tissue culture plates by fast-atom bombardment from a hexane precursor. Two osteoblast-like cell lines were cultured on uncoated and DLC-coated plates for periods of up to 72 h. The effects of DLC coatings on cellular metabolism were investigated by measuring the production of three osteoblast-specific marker proteins: alkaline phosphatase, osteocalcin, and type I collagen. There was no evidence that the presence of the DLC coating had any adverse effect on any of the parameters measured in this study. In a second series of experiments, DLC-coated cobalt-chromium cylinders were implanted in intramuscular locations in rats and in transcortical sites in sheep. Histologic analysis of specimens retrieved 90 days after surgery showed that the DLC-coated specimens were well tolerated in both sites. These data indicate that DLC coatings are biocompatible in vitro and in vivo, and further investigations into their long-term biological and tribological performance are now warranted.

Alkaline Phosphatase↗

The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2.

A hydroxyapatite/type I collagen (HAp/Col) composite, in which the hydroxyapatite nanocrystals align along the collagen molecules, has been prepared. The biocompatibility, osteoconductive activity, and efficacy as a carrier of recombinant human bone morphogenetic proteins (rhBMPs) of this novel biomaterial were examined. The composite material was implanted in the backs of Wistar rats, and specimens were collected for histological observations until week 24. In a second experiment, other samples of the composite material (5 x 5 x 10 mm3) were drilled and immersed in a solution of rhBMP-2 (0, 200, 400 microg/mL), and subsequently grafted in radii and ulnae in beagle dogs. As a control, three unfilled holes were left in one radius and ulna. X-ray images were prepared, and specimens collected for histological observation at weeks 8 and 12. Histological findings of the composites grafted in rats showed that the surface of the material was eroded as a result of macrophage infiltration. X-ray images and histological findings for the composites implanted in dogs support the idea that HAp/ Col has a high osteoconductive activity and is able to induce bone-remodeling units. In cases where the implants are grafted at weight bearing sites, treatment with rhBMP-2 at a dose of 400 microg/mL may be useful to shorten the time needed until bone union has occurred.

Animals↗

Biocompatible hydrogel supports the growth of respiratory epithelial cells: possibilities in tracheal tissue engineering.

Extensive tracheal defect reconstruction is a major challenge in plastic and reconstructive surgery. The lack of an epithelial lining on the luminal surfaces of tracheal prostheses is among the major causes of their failure. Chitosan-gelatin hydrogels were synthesized for the development of biocompatible, growth-supportive substrata for respiratory epithelial cells. We employed J774 macrophages to test the immunocompatibility of this gel. The hydrogel did not exert a cytotoxic effect on macrophages, as confirmed by tetrazolium reduction and neutral red uptake assay. Flow cytometric analysis of macrophages cultured on the hydrogel showed a comparable expression of activation markers CD11b/CD18, CD45, and CD14 to the control. Semiquantitative RT-PCR results showed an absence of upregulation of interleukin-6 (IL-6) and TNF-alpha in these macrophages with respect to the controls. Primary human respiratory epithelial cells cultured on the hydrogel showed proper attachment, normal morphology, and growth. A small proportion of cells on the hydrogel showed synchronously beating cilia. RT-PCR analysis showed that cells on the hydrogel expressed mucins 2 and 5 and cytokeratin 13, which are markers for secretory goblet and squamous cells, respectively. All these results demonstrate that the hydrogel supports the growth of a mixed population of differentiated epithelial cells. This hydrogel is suitable as a culture substratum for respiratory epithelial cells and could be used as a potential candidate for coating tracheal prostheses.

Biocompatible Materials↗

In vitro biocompatibility study of electrically conductive polypyrrole-coated polyester fabrics.

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.

Animals↗

Studies on in vitro evaluation for the biocompatibility of various biomaterials: inhibitory activity of various kinds of polymer microspheres on metabolic cooperation.

Gap junctional intercellular communication is a function that plays an important role in maintaining cell and tissue homeostasis and in regulating cell growth, development, and differentiation. Change in this function when contacting fibroblasts with various polymer microspheres was estimated using the metabolic cooperation assay system. When the cells were in contact with the microspheres after their adhesion onto a substrate, the function did not alter. However, when they were in contact with precoated microspheres on test dishes, the function was inhibited as the quantity of microspheres increased. Moreover, the inhibition level increased as the diameters of polyethylene and polystyrene microspheres decreased. However, no inhibition was observed if precoated microspheres were composed from poly(L-lactic acid). These findings suggest that the size and the material of microspheres, and how cells recognize the microspheres, are factors affecting cell function of gap junctional intercellular communication. Therefore, estimating this function may provide valuable information about the biocompatibility of many kinds of materials even in the form of particles.

Animals↗

A Schwann cell-seeded intrinsic framework and its satisfactory biocompatibility for a bioartificial nerve graft.

To optimize the internal environment of a collagen nerve tube, we designed a Schwann cell-seeded intrinsic framework and its biocompatibility was investigated. We fixed 6-0 polyglactin woven filaments (Vicryl) or polydioxanone monofilaments (PDS) on a silicone ring in a net fashion. It was coated with matrigel and then incubated with cultured newborn or adult Schwann cells. Furthermore, we implanted 1.5-cm-long filament-filled collagen tubes in a rat model. Using a live/dead fluorescent assay and electron microscopy, we found that adherent Schwann cells onto filaments remained viable and oriented longitudinally along filaments. The preliminary in vivo study indicated that a mild inflammatory reaction was present around the tube wall. However, nerve regeneration occurred around and between filaments. We concluded that the arrangement of Schwann cell columns onto filaments was achieved, mimicking Bünger bands. It was shown that the biomaterials did not impede nerve regeneration.

Animals↗

Biocompatible hemodialysis membranes for acute renal failure.

BACKGROUND: Acute renal failure (ARF) is associated with substantial morbidity and mortality. Some trials have reported a survival advantage among patients dialyzed with biocompatible membranes (BCM) compared to bioincompatible membranes (BICM). These findings were not consistently observed in subsequent studies. OBJECTIVES: To ascertain whether the use of BCM confers an advantage in either survival or recovery of renal function over the use of BICM in adult patients with ARF requiring intermittent hemodialysis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library - Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), the Mexican Index of Latin American Biomedical Journals IMBIOMED (1990 to January 2004), the Latin American and Caribbean Health Sciences Literature Database LILACS (1982 to January 2004), and reference lists of articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing the use of a BCM with a BICM in patients > 18 years of age with ARF requiring intermittent hemodialysis. DATA COLLECTION AND ANALYSIS: Two authors extracted the data independently. Cellulose-derived dialysis membranes were classified as BICM, and synthetic dialyzers were considered as BCM. The main outcomes were all-cause mortality and recovery of renal function by type of dialyzer. We further explored these outcomes according to the flux properties (high-flux or low-flux) of each of these dialyzers. A meta-analysis was conducted by combining data using a random-effects model. MAIN RESULTS: Nine studies were included in the primary analysis of mortality, with a total of 1062 patients. None of the pooled RR's reached statistical significance. The pooled relative risk (RR) for mortality was 0.93 (95% confidence interval (CI) = 0.81 to 1.07). The overall RR for recovery of renal function, inclusive of 1038 patients from nine studies was 1.09 (95% CI 0.90 to 1.31). The pooled RR for mortality by dialyzer flux property was 1.03 (95% CI 0.82 to 1.30). The RR for recovery of renal function by flux property was 0.85 (95% CI 0.55 to 1.31). A meta-analysis of mortality of kidney transplant recipients was not possible, but the analysis of recovery of renal function in this patient population was 1.09 (95% CI 0.91to 1.31). Results of sensitivity analyses did not differ significantly from the primary analyses. AUTHORS' CONCLUSIONS: There is no demonstrable clinical advantage to the use of BCM versus BICM in patients with ARF who require intermittent hemodialysis.

Acute Kidney Injury↗

Electroosmosis injection of blood serum into biocompatible microcapillary chip fabricated on quartz plate.

A chip which allows the detection of various human health markers from a trace amount of blood has been studied. As a goal, a microcapillary with a 30 x 30 microm cross-section was fabricated using all-dry etching technologies on a 2 x 2 cm SiO2 chip. The coating of the biocompatible 2-methacryloyloxyethylphosphorylcholine (MPC) polymer on the inner quartz wall of the microcapillary demonstrated a sufficiently long adsorption suppression of proteins in the serum on the quartz surface, while rapid stopping occurred for serum injected into the microcapillary with a bare quartz surface. The latter rapid stopping corresponded well to fast electroosmosis flow due to the negatively increasing zeta-potential by the adsorption of proteins on the quartz surface. The electroosmosis pump arranged a downstream of the microcapillary was also developed to inject serum into it. As a preliminary application, a given concentration-standard solution was injected into the ion-sensitive field-effect transistor (ISFET) embedded in the chip, employing the electroosmosis pump arranged downstream of the sensor position. Hence, the pH and Na+ and K+ cation concentrations were measured.

Blood Chemical Analysis↗

Compression of biocompatible liquid-filled HSA-alginate capsules: determination of the membrane mechanical properties.

Compression experiments between two parallel plates are performed on a series of biocompatible HSA-alginate capsules with two different membrane thicknesses. The capsule geometry and size as well as the average membrane thickness are first measured. The compression set-up is fitted with a sensitive force transducer that allows measurement of the compression force as a function of plate separation. The response of the capsule is analyzed by assuming different constitutive models for the membrane, where the shear and surface dilatation effects are accounted. An apparent area dilatation modulus is then computed for different values of the plate separation and required to remain constant as the capsule deformation increases. This allows identification of plausible constitutive laws for the membrane material.

Alginates↗

Production of different morphologies of biocompatible polymeric materials by supercritical CO(2) antisolvent techniques.

High-value biocompatible-polymers have been processed with supercritical antisolvent techniques to produce solid structures of different shape and size. In particular, a class of hyaluronic acid-derived polymers (Hyaff11-p100, Hyaff11-p80, Hyaff11-p75, Hyaff 302) have been used to obtain various morphologies such as microspheres, threads, fibers, networks, and sponges. The effect of thermodynamic variables on precipitation were highlighted in some preliminary batch experiments. Then, different products were obtained by tuning the values of operating parameters. Threads and fibers were the result of a continuous supercritical antisolvent (SAS) process where a concentrated polymer solution was pumped through a micrometric nozzle: The threads showed a reticular internal structure with an adjustable type of cavity. For production of networks and sponges, the concentration of polymer plays the key role. Below a critical value it was not possible to obtain a continuous network, while above it, a structure similar to that of the natural bone with three types of internal microporosity were obtained. Again, by tuning pressure and polymer concentration, the internal porosity could be controlled. Microparticles were also produced by the SAS process, and a control of their morphology was achieved by varying the concentration of the polymer in the starting solution and the density of organic solvent-CO(2) mixtures. All the products obtained by SAS have negligible content of residual solvent. A qualitative interpretation of experimental results is presented.

Biocompatible Materials↗

Unexpected improvement in stability and utility of cytochrome c by solution in biocompatible ionic liquids.

Proteins generally are only stable in vitro for short periods of time. This results in challenges during isolation and purification of recombinant proteins and reduces the shelf life of protein-based pharmaceuticals. Here we show that certain novel, biocompatible ionic liquids provide a stabilizing solvent for proteins, for example, cytochrome c, such that structure and activity are maintained even after 6 months of storage at room temperature. Normally, this protein would be rendered inactive after only 1 week in buffered aqueous solution. The effect of the ionic liquid solvent appears to be related to protection against hydrolysis.

Animals↗

Stenting very small coronary narrowings (< 2 mm) using the biocompatible phosphorylcholine-coated coronary stent.

Published data regarding stenting very small arteries are still limited. The BiodivYsio stent is a new stent coated with phosphorylcholine, a biocompatible molecule designed to reduce the formation of thrombus and potentially the risk of restenosis. The feasibility, safety, and efficacy of implantation of the 2.0 mm coated coronary stent were prospectively studied. We studied 97 patients from three centers who underwent elective, urgent, or bailout implantation of 106 BiodivYsio mini-stents (2.0 mm) in 101 lesions. Forty percent of lesions had unfavorable characteristics (type B2 or C) and 16% had thrombus and/or chronic total occlusion. Successful stent deployment was achieved in 100/101 lesions (99%). MLD increased from 0.49 +/- 0.31 mm to 1.89 +/- 0.41 mm and diameter stenosis decreased from 89% +/- 7% to 5.6% +/- 6%. Small vessel stenting was the only procedure in 71% patients. There was one acute stent thrombosis case. During 6-month follow-up, none died, one had MI, and one was referred to CABG due to nontarget lesion progression. Angiographic restenosis that required target lesion revascularization was performed in 8/18 that had catheterization due to chest pain or significant ischemia. Most patients improved in their clinical symptoms. The rate of major adverse cardiac events was 4.1% at 30-day and 10.3% at 6-month follow-up. This initial clinical experience indicates that the implantation of 2.0 mm stents coated with phosphorylcholine appears to be safe and efficacious in the treatment of complex coronary lesions and is associated with low target vessel revascularization rate in spite of the very small vessel diameter.

Adult↗

A bibliography of monographic works on biomaterials and biocompatibility.

Organizing and accessing biomaterials-related information is problematic because of the interdisciplinary nature of the field. Relevant information appears in the literature of numerous science and technology subdisciplines and there is no one index or database that covers all of the related publications. An additional barrier to information retrieval is the lack of a thesaurus for the field. Multiple terms representing the same concepts are currently employed and it is not always readily apparent which terms to use in a literature search. As an aid for students and researchers in the discipline, the author provides an indexed bibliography of English language monographic works on biomaterials and biocompatibility published after 1973.

Biocompatible Materials↗

Biocompatibility and in vivo gentamicin release from bioactive sol-gel glass implants.

Biomaterial pieces, with suitable osteogenic properties for use in the treatment of bone defects and the capability to avoid bone infections, have been synthesized. These materials are composed exclusively of gentamicin sulfate and bioactive SiO(2)-CaO-P(2)O(5) sol-gel glass (previously synthesized). Implant processing was achieved by uniaxial and isostatic pressure of the components mixture. After implanting the pieces into rabbit femur, we studied (i) the antibiotic release, determining the concentration in proximal and distal bone, liver, kidney, and lung as a function of time; and (ii) the bone growth resulting from the glass reactivity in the biologic environment. The results indicate that the implants are good carriers for local gentamicin release in the osseous tissue, exhibiting excellent biocompatibility and bone integration. Moreover, these implants are able to promote bone growth during their resorption process.

Animals↗

New acrylic bone cements conjugated to vitamin E: curing parameters, properties, and biocompatibility.

Acrylic bone cement formulations with antioxidant character were prepared by incorporation of a methacrylic monomer derived from vitamin E (MVE). Increasing concentrations of this monomer provided decreasing peak temperature values, ranging from 62 to 36 degrees C, and increasing setting time with values between 17 and 25 min. Mechanical properties were evaluated by compression and tension tests. Compressive strength of the new formulations were superior to 70 MPa in all cases. The cement containing 25 wt % MVE, however, showed a significant decrease in tensile properties. Biocompatibility of the new formulations was studied in vitro. The analysis of the effect of leachables from cements into the media showed continued cell proliferation and cell viability with a significant increase for the cement containing 15 wt % MVE. This formulation also showed a significant increase in cellular proliferation over a period of 7 days as indicated by the Alamar Blue test. The cells were able to differentiate and express phenotypical markers in presence of all materials. A significant increase in alkaline phosphatase activity was observed on the cements prepared in presence of 15-25 wt % MVE compared with PMMA. Morphological assessment showed that the human osteoblast (HOB) cells were able to adhere, retain their morphology, and proliferate on all the cements.

Acrylates↗

Biocompatible microcapsules with enhanced mechanical strength.

A block copolymer, (short-chain alginate)-co-MPEG, was synthesized and used for coating the capsular membranes of the photosensitive microcapsules. The resulted microcapsules exhibited an excellent mechanical strength. The permeability test results revealed that the capsular membrane was freely permeable to cytochrome C and myoglobin, less permeable to serum albumin, and almost impermeable to IgG. In the cell attachment test, the results showed that the surface formed by (short-chain alginate)-co-MPEG copolymer could effectively reduce cell adhesion as compared to poly(L-lysine) and alginate. The microcapsules were evaluated by intraperitoneal implantation experiment of mice. The results demonstrated that microcapsules coated with (short-chain alginate)-co-MPEG were more biocompatible than the conventional alginate/PLL/alginate microcapsules.

3T3 Cells↗