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Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly(lactide-co-glycolide) microspheres.

We have assessed the biocompatibility of a new composite bone graft consisting of calcium phosphate cement (CPC) and poly(lactide-co-glycolide) (PLGA) microspheres (approximate diameter of 0.18-0.36 mm) using cell culture techniques. CPC powder is mixed with PLGA microspheres and water to yield a workable paste that could be sculpted to fit the contours of a wound. The cement then hardens into a matrix of hydroxyapatite microcrystals containing PLGA microspheres. The rationale for this design is that the microspheres will initially stabilize the graft but can then degrade to leave behind macropores for colonization by osteoblasts. The CPC matrix could then be resorbed and replaced with new bone. In the present study, osteoblast-like cells (MC3T3-E1 cells) were seeded onto graft specimens and evaluated with fluorescence microscopy, environmental scanning electron microscopy and the Wst-1 assay (an enzymatic assay for mitochondrial dehydrogenase activity). Cells were able to adhere, attain a normal morphology, proliferate and remain viable when cultured on the new composite graft (CPC-PLGA) or on a control graft (CPC alone). These results suggest that our new cement consisting of CPC and PLGA microspheres is biocompatible. This is the first time that a 'polymer-in-mineral' (PLGA microspheres dispersed in a CPC matrix) cement has been formulated that is moldable, resorbable and that can form macropores after the cement has set.

Animals↗

Biocompatibility of hydrophilic intraocular lenses.

PURPOSE: To assess the biocompatibility of 3 hydrophilic acrylic intraocular lenses (IOLs) by evaluating the postoperative cell reaction on the IOL surface, anterior capsule opacification (ACO) rate, and presence of membrane growth over the anterior IOL surface. SETTING: University Eye Clinic of Trieste, Trieste, Italy. METHODS: In this prospective study, 73 patients were randomized to receive 1 of 3 types of hydrogel IOLs after phacoemulsification: Storz Hydroview H60M, Corneal ACR6D, or Ioltech Stabibag. To analyze and photograph the anterior IOL surface, slitlamp biomicroscopy and specular microscopy were performed 7, 30, 90, and 180 days after surgery. Small, epithelioid, and giant inflammatory cell reaction was evaluated. In addition, ACO and membrane growth on the anterior IOL surface were assessed. RESULTS: Low inflammatory cell adhesion was observed on the anterior surface of all 3 IOLs. The Stabibag group had a significantly higher grade of small inflammatory cell reaction 7 and 30 days after surgery. A significantly higher rate of ACO was observed in the ACR6D group. The Hydroview and ACR6D groups had a significantly higher percentage of membrane growth from the capsulorhexis edge onto the anterior IOL surface than the Stabibag group. CONCLUSIONS: Clinically, the 3 hydrophilic IOLs behaved in a different manner, showing the different forms of biocompatibility. Results indicate that a different chemical composition determines correspondingly different protein absorption on IOL surfaces. This might result in a different adhesion pattern and spreading of lens epithelial and inflammatory cells.

Acrylic Resins↗

Biocompatibility of surface-modified intraocular lenses.

We evaluated the biocompatibility of three kinds of intraocular lenses: heparin-surface-modified, surface-passivated, and regular poly(methyl methacrylate). Each lens type was implanted in 30 eyes. The cases were followed for one year. Biocompatibility was assessed by the degree of postoperative inflammation and capsule opacification. There was no significant difference between the surface-passivated and regular groups on both indices, but there was less postoperative inflammation in the heparin-surface-modified group. The incidence of posterior capsule opacification was greater in the heparin-surface-modified group than in the surface-passivated and regular groups, but the difference was not statistically significant.

Aged↗

In vitro organotypic culture method to evaluate the biocompatibility of heparin-surface-modified intraocular lenses.

Using an organotypic culture method, we evaluated the biocompatibility of two kinds of intraocular lenses: conventional poly(methyl methacrylate) (PMMA) and heparin-surface-modified (HSM) PMMA. Chicken corneal endothelium from embryos incubated for 14 days was placed on an agar medium and covered with one of three types of materials: PMMA, HSM PMMA, and a control, Thermanox. Experiments at five different times measured cell migration, cell multiplication, and cell adhesion. Scanning electron microscopy showed a low level of corneal endothelial adhesion on the HSM IOL surface. There was a significant difference between the HSM and untreated lenses in migration surface and cell density, with the HSM lenses having better biocompatibility.

Animals↗

Long-term results and biocompatibility of heparin-surface-modified intraocular lenses.

A prospective in vivo study of 50 intraocular lenses was done to document the long-term results and biocompatibility of heparin-surface-modified poly(methyl methacrylate) posterior chamber lenses. Continuous curvilinear capsulorhexis and phacoemulsification were performed throughout and examinations were by slit-lamp and specular microscopy. Decentrations of more than 1 mm were seen in 4% of eyes. Stress folds from the haptic traction forces were detected in 16%. A posterior capsulotomy was performed in 10% because of fibrosis or Elschnig pearl formation. Fine fibers were found on the lens surface in 76%. During the first postoperative days only a moderate number of fibroblast-like cells was observed. Foreign-body giant cells were seen in 8%. All cases with foreign-body giant cells had posterior synechias. Visual performance and clinical results were comparable to those of other well-approved intraocular lenses. The low percentage of cellular reaction on the lens surface suggests good biocompatibility.

Adult↗

Biocompatibility of poly(methyl methacrylate), silicone, and AcrySof intraocular lenses: randomized comparison of the cellular reaction on the anterior lens surface.

PURPOSE: To determine the foreign-body response to three intraocular lens (IOL) biomaterials (poly[methyl methacrylate] [PMMA], silicone, and AcrySof) and use this as an indicator of their comparative biocompatibility postoperatively within the eye. SETTING: A British teaching hospital eye department. METHODS: Ninety eyes were prospectively randomized to receive a PMMA, silicone, or AcrySof IOL. All lenses had 6.0 mm optics with PMMA haptics. A standardized surgical protocol was performed by a single surgeon using an extracapsular technique with capsulorhexis; eyes that experienced a surgical complication were excluded. All patients had standardized postoperative medication and follow-up. Specular microscopy of the anterior IOL surface was carried out after pupil dilation on days 1, 7, 30, 90, 180, 360, and 720 to assess small cell and giant cell reactions. RESULTS: All three IOL types produced a mild degree of nonspecific foreign-body response, which resolved over the study period without detrimental effect. The silicone group had significantly higher small cell counts than the PMMA and AcrySof groups (P = .02); the AcrySof group had significantly lower giant cell counts than the other two groups (P = .003). CONCLUSION: The three IOL types were sufficiently biocompatible to function in normal eyes with age-related cataracts. However, AcrySof IOLs were associated with lower giant cell counts than PMMA and silicone IOLs and might produce better results in eyes with pre-existing blood-aqueous barrier damage.

Acrylates↗

A longitudinal comparative histometric study of the biocompatibility of three local hemostatic agents.

The biocompatibility was studied of 3 hemostatic agents (Astroplast, Hemastogen and bone wax) implanted into experimental bone cavities together with their clearance from the implantation sites. The 3 agents had an acceptable hemostatic effect during the surgical procedure. However, marked differences regarding tissue reactions in the experimental bone cavities, as well as at the internal bone surfaces, were found between them. Astroplast and Hemastogen appear to provoke more adverse tissue reactions, including foreign body giant cell formation, compared with bone wax. All 3 hemostatic implants showed markedly delayed bone healing. It was concluded that their biocompatibility was not ideal but acceptable in view of the clinical advantages.

Alginates↗

Study of the biodegradation and in vivo biocompatibility of novel biomaterials.

The degradation of two rosin-based biomaterials, the glycerol ester of maleic rosin (GMR) and the pentaerythritol ester of maleic rosin (PMR), was examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a subcutaneous rat model. Free films of the two biomaterials with mean thickness 0.4+/-0.02 mm were used for the study. The initial biocompatibility was followed by microscopic examination of the inflammatory tissue response to the implanted films. Sample weight loss and molecular weight decline of the free films was used to monitor the degradation quantitatively, while surface morphological changes were analysed for qualitative estimation. Biocompatibility response was followed on post-operative days 7, 14, 21 and 28 and compared with those of poly(DL-lactic-co-glycolic acid) (PLGA) (50:50) films. Both biomaterials showed slow in vitro degradation when compared with the in vivo rate. The mechanism followed was, however, bulk degradation of the films. The penta-esterified form of maleic rosin was observed to degrade more rapidly than glycerol esterified maleic rosin. The acute and subacute inflammatory reactions were characterized by fibrosis at the end of 28 days. The biomaterials showed reasonable tissue tolerance to the extent evaluated. There was a total absence of tissue necrosis or abscess formation for all implanted films. The response, although not identical to that of PLGA, is reasonable, promising new drug delivery applications for rosin biomaterials.

Animals↗

Biocompatible photolithographic process for the patterning of biomolecules.

A new approach for the patterning of biomolecule layers is introduced based on the design of a new photoresist material with biocompatible lithographic processing requirements. The photoresist is based on poly(t-butyl acrylate), which allows positive imaging with very dilute basic solutions, tolerable by selected biomolecules used in immunoanalysis. Sensitivity at lambda>300 nm is obtained using a suitable sulfonium salt photoacid generator. Thermal steps also take place under conditions tolerable by biomolecules. Lithographic results on Si wafer substrates show resolution capabilities for equal lines/spaces, down to the range of 5-10 microm under biocompatible conditions. The process is also used on substrates of different geometries, including inner capillary surfaces. The patterning of the inner surface of a polystyrene capillary with mouse IgG is reported to demonstrate the principles of the above approach.

Animals↗

Comparison of the intraosseous biocompatibility of Vitremer and super EBA by implantation into the mandible of rabbits.

OBJECTIVES: This study compared the intraosseous biocompatibility of Vitremer, a new hydrophilic glass-ionomer cement, to that of Super EBA. STUDY DESIGN: Twenty-two New Zealand rabbits were anesthetized, the mandibular bone exposed, and two holes were drilled through the cortical plate. The materials were loaded into silicone carriers and inserted into the mandibles. Eleven rabbits were killed 4 weeks after implantation, 11 animals after 12 weeks. The mandibles were prepared with standard histologic procedures; the tissue reactions were graded from none to very severe. RESULTS: At 4 weeks Vitremer implants showed very slight to slight reactions, and the Super EBA implants showed slight reactions and one moderate reaction with no significant difference between the two materials. At 12 weeks, bone healing had occurred, despite the persistence of some fibrous tissue interposition. The reactions were classified as none to very slight for Vitremer and very slight to slight for EBA. Statistical analysis showed better results for Vitremer at 12 weeks. CONCLUSION: The intraosseous biocompatibility of Vitremer was similar at 4 weeks and superior at 12 weeks to that of Super EBA. Its other properties should be evaluated before considering its use in clinical practice.

Animals↗

Biocompatibility studies of titanium-based alloy pedicle screw and rod system: histological aspects.

BACKGROUND CONTEXT: Few histological studies of pedicle screw and rod systems have been done, and spinal surgery with pedicle screw and rod system is increasing. PURPOSE: To know the biocompatibility of pedicle screw and rod systems histologically. STUDY DESIGN/SETTING: Titanium-based alloy pedicle screws were removed from 20 patients. Histological studies of the tissue response to the screws were performed by light microscopy. PATIENT SAMPLE: Twenty patients, who were diagnosed with burst type spinal fracture, spondylolysis, spondylolisthesis, and lumbar disc herniation. OUTCOME MEASURES: All slides were observed by light microscopy, and inflammation, fibrous tissue formation, and wear debris were evaluated using a subjective scale. METHODS: Before the surgery, plain radiographs were taken to confirm the solid arthrodesis. Histological analysis was divided into four areas and studied using light microscopy. RESULTS: Inflammation and fibrous tissue formation were the main tissue reactions to the implants. No tissue surrounding the implants showed irreversible changes. Fibrous tissue was often observed at the bone-screw interface without direct contact of screw and bone at the muscle-screw interface histologically. Although some titanium debris was observed in both interfaces, no debris of inflammatory cells were seen at 1 cm distance from the screws. The inflammatory response to the screw debris was localized. CONCLUSIONS: Titanium-based alloy pedicle screws produced some metal debris and caused localized inflammation. No adverse tissue reaction was observed around the screws and rods. Direct contact without any fibrous tissue formation at the bone-screw interface was observed in some patients. A titanium-based alloy pedicle screw and rod system is considered biocompatible histologically.

Adult↗

Synthetic biocompatible cyclodextrin-based constructs for local gene delivery to improve cutaneous wound healing.

The localized, sustained delivery of growth factors for wound healing therapy is actively being explored by gene transfer to the wound site. Biocompatible matrices such as bovine collagen have demonstrated usefulness in sustaining gene therapy vectors that express growth factors in local sites for tissue repair. Here, new synthetic biocompatible materials are prepared and shown to deliver a protein to cultured cells via the use of an adenoviral delivery vector. The synthetic construct consists of a linear, beta-cyclodextrin-containing polymer and an adamantane-based cross-linking polymer. When the two polymers are combined, they create an extended network by the formation of inclusion complexes between the cyclodextrins and adamantanes. The properties of the network are altered by controlling the polymer molecular weights and the number of adamantanes on the cross-linking polymer, and these modifications and others such as replacement of the beta-cyclodextrin (host) and adamantane (guest) with other cyclodextrins (hosts such as alpha, gamma, and substituted members) and inclusion complex forming molecules (guests) provide the ability to rationally design network characteristics. Fibroblasts exposed to these synthetic constructs show proliferation rates and migration patterns similar to those obtained with collagen. Gene delivery (green fluorescent protein) to fibroblasts via the inclusion of adenoviral vectors in the synthetic construct is equivalent to levels observed with collagen. These in vitro results suggest that the synthetic constructs are suitable for in vivo tissue repair applications.

Biocompatible Materials↗

Synthesis of well-defined amphiphilic block copolymers having phospholipid polymer sequences as a novel biocompatible polymer micelle reagent.

To realize safer and effective drug administration, novel well-defined and biocompatible amphiphilic block copolymers containing phospholipid polymer sequences were synthesized. At first, the homopolymer of 2-methacryloyloxyethylphosphorylcholine (MPC) was synthesized in water by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. The "living" polymerization was confirmed by the fact that the number-average molecular weight increased linearly with monomer conversion while the molecular weight distribution remained narrow independent of the conversion. The poly(MPC) thus prepared is end-capped with a dithioester moiety. Using the dithioester-capped poly(MPC) as a macro chain transfer agent, AB diblock copolymers of MPC and n-butyl methacrylate (BMA) were synthesized. Associative properties of the amphiphilic block copolymer (pMPC(m)-BMA(n)) with varying poly(BMA) block lengths were investigated using NMR, fluorescence probe, static light scattering (SLS), and quasi-elastic light scattering (QELS) techniques. Proton NMR data in D2O indicated highly restricted motions of the n-butyl moieties, arising from hydrophobic associations of poly(BMA) blocks. Fluorescence spectra of N-phenyl-1-naphthylamine indicated that the probes were solubilized in the polymer micelles in water. The formation of polymer micelles comprising a core with poly(BMA) blocks and shell with hydrophilic poly(MPC) blocks was suggested by SLS and QELS data. The size and mass of the micelle increased with increasing poly(BMA) block length. With an expectation of a pharmaceutical application of pMPC(m)-BMA(n), solubilization of a poorly water-soluble anticancer agent, paclitaxel (PTX), was investigated. PTX dissolved well in aqueous solutions of pMPC(m)-BMA(n) as compared with pure water, implying that PTX is incorporated into the hydrophobic core of the polymer micelle. Since excellent biocompatible poly(MPC) sequences form an outer shell of the micelle, pMPC(m)-BMA(n) may find application as a promising reagent to make a good formulation with a hydrophobic drug.

Antineoplastic Agents↗

Synthesis, material properties, and biocompatibility of a novel self-cross-linkable poly(caprolactone fumarate) as an injectable tissue engineering scaffold.

A novel self-cross-linkable and biodegradable macromer, poly(caprolactone fumarate) (PCLF), has been developed for guided bone regeneration. This macromer is a copolymer of fumaryl chloride, which contains double bonds for in-situ cross-linking, and poly(epsilon-caprolactone), which has a flexible chain to facilitate self-cross-linkability. PCLF was characterized with Fourier transform infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and gel permeation chromatography. Porous scaffolds were fabricated with sodium chloride particles as the porogen and a chemical initiation system. The PCLF scaffolds were characterized with scanning electron microscopy and micro-computed-tomography. The cytotoxicity and in vivo biocompatibility of PCLF were also assessed. Our results suggest that this novel copolymer, PCLF, is an injectable, self-cross-linkable, and biocompatible macromer that may be potentially used as a scaffold for tissue engineering applications.

Animals↗

pH-sensitive vesicles based on a biocompatible zwitterionic diblock copolymer.

Highly biocompatible pH-sensitive diblock copolymer vesicles were prepared from the self-assembly of a biocompatible zwitterionic copolymer, poly[2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate], PMPC-b-PDPA. Vesicle formation occurred spontaneously by adjusting the solution pH from pH 2 to above 6, with the hydrophobic PDPA chains forming the vesicle walls. Transmission electron microscopy (TEM), dynamic laser light scattering (DLS), and UV-visible absorption spectrophotometry were used to characterize these vesicles. Gold nanoparticle-decorated vesicles were also obtained by treating the vesicles with HAuCl4, followed by NaBH4.

Biocompatible Materials↗

Biocompatible heterostructured nanoparticles for multimodal biological detection.

Hybrid nanoparticles are of significant interest primarily because of their innate multifunctional capabilities. These capabilities can be exploited when hybrid nanoparticles are used for applications in the biomedical sciences in particular, where they are utilized as multimodal nanoplatforms for sensing, imaging, and therapy of biological targets. However, the realization of their biomedical applications has been difficult, in part because of a lack of high quality hybrid nanoparticles which possess high aqueous colloidal stability and biocompatibility while retaining their multifunctionalities. Here, we present the development of inorganic heterodimer nanoparticles of FePt-Au with multifunctional capabilities including catalytic growth effects, magnetic resonance (MR) contrast effects, optical signal enhancing properties, and high colloidal stability and biocompatibility. Their multimodal capabilities for biological detection are demonstrated through their utilizations in the patterned biochip based detection of avidin-biotin interaction as well as in molecular MR imaging of neuroblastoma cells.

Biocompatible Materials↗

Poly(L-lactide) (PLLA)/multiwalled carbon nanotube (MWCNT) composite: characterization and biocompatibility evaluation.

Much effort has been directed at the fabrication of carbon nanotubes (CNTs)/polymer composites and the characterization of their physical properties. Among them, composites comprising CNTs and the biocompatible polymers are of special interest due to their potential for specific biomedical applications. we report the preparation of the MWCNT/poly(L-lactide) composite and the corresponding spectroscopic (Raman) and the microscopic (SEM, TEM) characterization. The electronic transport, thermal properties, and biocompatibility of this composite have also been investigated. The Raman spectroscopic analysis suggests the interaction between PLLA and MWCNT occurs mainly through the hydrophobic C-CH3 functional groups. The DC conductivity of the composite increases as the MWCNT loading is increased. Such behavior can be described by a percolation mechanism in which a percolation threshold at about 14 wt % MWCNT loading is observed with the maximum end conductivity of 0.1 S x cm(-1). The DSC study of the PLLA/MWCNT composite reveals that the MWCNTs in the composite have the effect of inducing crystallization and plasticizing the polymer matrix. The results from the cell culture test suggest that the presence of MWCNT in the composite inhibits the growth of the fibroblast cells.

Biocompatible Materials↗

Surfactant-assisted synthesis of water-soluble and biocompatible semiconductor quantum dot micelles.

We report a simple, rapid approach to synthesize water-soluble and biocompatible fluorescent quantum dot (QD) micelles by encapsulation of monodisperse, hydrophobic QDs within surfactant/lipid micelles. Analyses of UV-vis and photo luminescence spectra, along with transmission electron microscopy, indicate that the water-soluble semiconductor QD micelles are monodisperse and retain the optical properties of the original hydrophobic QDs. The QD micelles were shown to be biocompatible and exhibited little or no aggregation when taken up by cultured rat hippocampal neurons.

Animals↗