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Biomedical subjects

Eric J Beckman

Publications and source records attributed to Eric J Beckman.

10 recordsLinked to original sources

Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether ester) triblock copolymers and putrescine: synthesis, characterization and cytocompatibility.

Polymers with elastomeric mechanical properties, tunable biodegradation properties and cytocompatibility would be desirable for numerous biomedical applications. Toward this end a series of biodegradable poly(ether ester urethane)urea elastomers (PEEUUs) based on poly(ether ester) triblock copolymers were synthesized and characterized. Poly(ether ester) triblock copolymers were synthesized by ring-opening polymerization of epsilon-caprolactone with polyethylene glycol (PEG). PEEUUs were synthesized from these triblock copolymers and butyl diisocyanate, with putrescine as a chain extender. PEEUUs exhibited low glass transition temperatures and possessed tensile strengths ranging from 8 to 20MPa and breaking strains from 325% to 560%. Increasing PEG length or decreasing poly(caprolactone) length in the triblock segment increased PEEUU water absorption and biodegradation rate. Human umbilical vein endothelial cells cultured in a medium supplemented with PEEUU biodegradation solution suggested a lack of degradation product cytotoxicity. Endothelial cell adhesion to PEEUUs was less than 60% of tissue culture polystyrene and was inversely related to PEEUU hydrophilicity. Surface modification of PEEUUs with ammonia gas radio-frequency glow discharge and subsequent immobilization of the cell adhesion peptide Arg-Gly-Asp-Ser increased endothelial adhesion to a level equivalent to tissue culture polystyrene. These biodegradable PEEUUs thus possessed properties that would be amenable to applications where high strength and flexibility would be desirable and exhibited the potential for tuning with appropriate triblock segment selection and surface modification.

Absorbable Implants↗

A biodegradable polyurethane-ascorbic acid scaffold for bone tissue engineering.

A novel, nontoxic, biodegradable, sponge-like polyurethane scaffold was synthesized from lysine-di-isocyanate (LDI) and glycerol. Ascorbic acid (AA) was copolymerized with LDI-glycerol. Our hypothesis was that the AA-containing polymer foam would enhance the biological activity of the osteoblastic precursor cell (OPCs). The LDI-glycerol-AA matrix degraded in aqueous solution to the nontoxic products of lysine, glycerol, and AA. The degradation products did not significantly affect the solution pH. The physical properties of the polymer network supported the cell growth in vitro. Mouse OPCs attached to the polymer matrix and remained viable. OPCs produced multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, AA release stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis. Cells grown on the LDI-glycerol-AA matrix also showed an enhancement of mRNA expression for pro-alpha1 (I) collagen and transforming growth factor-alpha1 after 1 week. Data were tested for significance with an analysis of variance model and multiple comparison test (Fisher's Protected Least Significant Difference) at p < or = 0.05. The observations suggest that AA-containing polyurethane may be useful in bone tissue engineering applications.

Alkaline Phosphatase↗

Three-dimensional biocompatible ascorbic acid-containing scaffold for bone tissue engineering.

A biodegradable, biocompatible, ascorbic acid-containing three-dimensional polyurethane matrix was developed for bone tissue-engineering scaffolds. This matrix was synthesized with lysine-di-isocyanate (LDI), ascorbic acid (AA), glycerol, and polyethylene glycol (PEG). LDI-glycerol-PEG-AA prepolymer when reacted with water foamed with the liberation of CO(2) to provide a pliable, spongy urethane polymer with pore diameters of 100 to 500 microm. The LDI-glycerol-PEG-AA matrix degraded in aqueous solution and yielded lysine, glycerol, PEG, and ascorbic acid as breakdown products. The degradation products did not significantly affect the solution pH. The LDI-glycerol-PEG-AA matrix can be fabricated into diverse scaffold dimensions and the physicochemical properties of the polymer network supported in vitro cell growth. Green fluorescent protein-transgenic mouse bone marrow cells (GFP-MBMCs) attached to the polymer matrix and remained viable, and the cells became confluent cultures. Furthermore, ascorbic acid released from LDI-glycerol-PEG-AA matrix stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis in vitro. Cells grown on LDI-glycerol-PEG-AA matrix did not differ phenotypically from cells grown on tissue culture polystyrene plates as assessed by cell growth, expression of mRNA for collagen type I, and transforming growth factor beta(1). These observations suggest that AA-containing polyurethane may be useful in bone tissue-engineering applications.

Absorbable Implants↗

Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester-urethane)ureas based on poly(caprolactone) and putrescine.

The engineering of tissue for mechanically demanding applications in the cardiovascular system is likely to require mechanical conditioning of cell-scaffold constructs prior to their implantation. Scaffold properties amenable to such an application include high elasticity and strength coupled with controllable biodegradative and cell-adhesive properties. To fulfill such design criteria, we have synthesized a family of poly(ester-urethane)ureas (PEUUs) from polycaprolactone and 1,4-diisocyanatobutane. Lysine ethyl ester (Lys) or putrescine was used as chain extenders. To encourage cell adhesion, PEUUs were surface modified with radio-frequency glow discharge followed by coupling of Arg-Gly-Asp-Ser (RGDS). The synthesized PEUUs were highly flexible, with breaking strains of 660-895% and tensile strengths from 9.2-29 MPa. Incubation in aqueous buffer for 8 weeks resulted in mass loss, from >50% (Lys chain extender) to 10% (putrescine chain extender). Human endothelial cells cultured for 4 days with medium containing the degradation products from PEUUs with either the Lys or putrescine chain extender showed no toxic effects. Cell adhesion was 85% of that measured on tissue-culture polystyrene for unmodified PEUU surfaces (p < 0.01) and >160% (p < 0.001) of polystyrene on RGDS-modified PEUUs. These biodegradable PEUUs demonstrate potential for future application as cell scaffolds in cardiovascular tissue-engineering or other soft-tissue applications.

Absorbable Implants↗

Fluorinated NAD as an affinity surfactant.

Nicatinamide adenine dinucleotide (NAD) with an attached perfluoropolyether tail acts as an affinity surfactant in the extraction of the enzyme horse liver alcohol dehydrogenase (HLADH) from an aqueous medium into a fluorous solvent.

Ethers↗

H(2)O(2) in CO(2): sustainable production and green reactions.

Hydrogen peroxide is a "green" oxidant whose relatively high cost has prevented it from being applied to commodity chemical processing. Interestingly, those attributes of the current H(2)O(2) process that contribute to the high cost also contribute to its nonsustainable features. We have consequently explored the generation of hydrogen peroxide both by the AQ route and directly from hydrogen and oxygen using liquid CO(2) as the solvent, because CO(2) provides some unique advantages to H(2)O(2) synthesis.

Carbon Dioxide↗

Polyethylene glycol diisocyanate decreases platelet deposition after balloon injury of rabbit femoral arteries.

BACKGROUND: Platelet deposition after angioplasty remains problematic and may contribute to intimal hyperplasia and restenosis. We proposed that polyethylene glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages with amine residues on proteins, could mask thrombogenic vascular wall proteins from platelets, thereby abrogating acute platelet deposition. METHODS AND RESULTS: To test this hypothesis, we isolated the femoral arteries of 10 New Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter which was inserted through a distal arteriotomy. Immediately after balloon injury, (111)indium-labeled autologous platelets were infused peripherally and the injured femoral arteries were randomly treated for 1 minute with a PEG-DISO solution in one artery and a control solution of the phosphate buffered saline vehicle in the contralateral artery. Following treatment, reflow was initiated. The vessels were harvested after 1 hour and radioactivity was quantified in a gamma counter. Platelet counts were standardized by weight and expressed as platelets/mg (mean +/- SEM). Platelet deposition onto arteries treated with PEG-DISO was (1.2 +/- 0.5) x 10(6) platelets/mg compared to (5.6 +/- 4.2) x 10(6) platelets/mg onto the contralateral control arteries treated with vehicle (P < 0.005). Scanning electron micrographs of the injured vessel segment confirmed qualitatively less platelet deposition on the treated segments than on the control segments. CONCLUSION: Treatment with PEG-DISO significantly inhibited platelet deposition after vascular injury. These data support the hypothesis that treatment with PEG-DISO masks surface adhesive proteins from platelet receptors in vivo and that the resulting molecular barrier significantly reduces platelet deposition onto the damaged vessel wall for at least one hour. The formation of a molecularly thin barrier to platelet deposition may thus be a novel and effective treatment to abrogate acute intravascular thrombosis and may have value in the treatment of restenosis.

Angioplasty, Balloon↗

Synthesis, biodegradability, and biocompatibility of lysine diisocyanate-glucose polymers.

The success of a tissue-engineering application depends on the use of suitable biomaterials that degrade in a timely manner and induce the least immunogenicity in the host. With this purpose in mind, we have attempted to synthesize a novel nontoxic biodegradable lysine diisocyanate (LDI)- and glucose-based polymer via polymerization of highly purified LDI with glucose and its subsequent hydration to form a spongy matrix. The LDI-glucose polymer was degradable in aqueous solutions at 37, 22, and 4 degrees C, and yielded lysine and glucose as breakdown products. The degradation products of the LDI-glucose polymer did not significantly affect the pH of the solution. The physical properties of the polymer were found to be adequate for supporting cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSCs) attached to the polymer matrix, remained viable on its surface, and formed multilayered confluent cultures with retention of their phenotype over a period of 2 to 4 weeks. These observations suggest that the LDI-glucose polymer and its degradation products were nontoxic in vitro. Further examination in vivo over 8 weeks revealed that subcutaneous implantation of hydrated matrix degraded in vivo three times faster than in vitro. The implanted polymer was not immunogenic and did not induce antibody responses in the host. Histological analysis of the implanted polymer showed that LDI-glucose polymer induced a minimal foreign body reaction, with formation of a capsule around the degrading polymer. The results suggest that biodegradable peptide-based polymers can be synthesized, and may potentially find their way into biomedical applications because of their biodegradability and biocompatibility.

Biocompatible Materials↗