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Injectable polyurethane composite scaffolds delay wound contraction and support cellular infiltration and remodeling in rat excisional wounds.
Adolph EJ, Hafeman AE, Davidson JM, Nanney LB, Guelcher SA
(2012) J Biomed Mater Res A 100: 450-61
MeSH Terms: Animals, Apoptosis, Carboxymethylcellulose Sodium, Cell Proliferation, Collagen, Disease Models, Animal, Hyaluronic Acid, Immunohistochemistry, Injections, Isocyanates, Ki-67 Antigen, Lysine, Male, Polyethylene Glycols, Polyurethanes, Rats, Sprague-Dawley, Rheology, Tissue Scaffolds, Wound Healing, Wounds and Injuries
Show Abstract · Added May 28, 2014
Injectable scaffolds present compelling opportunities for wound repair and regeneration because of their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane (PUR) biocomposite scaffolds and their application in cutaneous wound repair using a rat excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat excisional wound model, injection of settable biocomposite scaffolds stented the wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of wound length and thickness revealed that the treated wounds were less contracted at day 7 compared to blank wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable PUR biocomposite scaffold that enhances cutaneous wound healing in a rat model.
Copyright © 2011 Wiley Periodicals, Inc.
1 Communities
2 Members
0 Resources
20 MeSH Terms
Injectable biodegradable polyurethane scaffolds with release of platelet-derived growth factor for tissue repair and regeneration.
Hafeman AE, Li B, Yoshii T, Zienkiewicz K, Davidson JM, Guelcher SA
(2008) Pharm Res 25: 2387-99
MeSH Terms: Absorbable Implants, Animals, Biomechanical Phenomena, Bone Regeneration, Cell Line, Cross-Linking Reagents, Drug Carriers, Elasticity, Hydrolysis, Injections, Subcutaneous, Isocyanates, Kinetics, Male, Mice, Osteoblasts, Platelet-Derived Growth Factor, Polyurethanes, Porosity, Rats, Rats, Sprague-Dawley, Solubility, Temperature, Tissue Engineering, Tissue Scaffolds
Show Abstract · Added December 10, 2013
PURPOSE - The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering.
METHODS - Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured.
RESULTS - Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter.
CONCLUSIONS - Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering.
1 Communities
2 Members
0 Resources
24 MeSH Terms
Synthesis, mechanical properties, biocompatibility, and biodegradation of polyurethane networks from lysine polyisocyanates.
Guelcher SA, Srinivasan A, Dumas JE, Didier JE, McBride S, Hollinger JO
(2008) Biomaterials 29: 1762-75
MeSH Terms: 3T3 Cells, Absorbable Implants, Animals, Biocompatible Materials, Bone Substitutes, Cell Adhesion, Cell Line, Compressive Strength, Elasticity, Hardness, Isocyanates, Lysine, Materials Testing, Mice, Stress, Mechanical
Show Abstract · Added February 23, 2016
Bone defects, such as compressive fractures in the vertebral bodies, are frequently treated with acrylic bone cements (e.g., PMMA). Although these biomaterials have sufficient mechanical properties for fixing the fracture, they are non-degradable and do not remodel or integrate with host tissue. In an alternative approach, biodegradable polyurethane (PUR) networks have been synthesized that are designed to integrate with host tissue and degrade to non-cytotoxic decomposition products. PUR networks have been prepared by two-component reactive liquid molding of low-viscosity quasi-prepolymers derived from lysine polyisocyanates and poly(epsilon-caprolactone-co-DL-lactide-co-glycolide) triols. The composition, thermal transitions, and mechanical properties of the biomaterials were measured. The values of Young's modulus ranged from 1.20-1.43 GPa, and the compressive yield strength varied from 82 to 111 MPa, which is comparable to the strength of PMMA bone cements. In vitro, the materials underwent controlled biodegradation to non-cytotoxic decomposition products, and supported the attachment and proliferation of MC3T3 cells. When cultured in osteogenic medium on the PUR networks, MC3T3 cells deposited mineralized extracellular matrix, as evidenced by von Kossa staining and tetracycline labeling. Considering the favorable mechanical and biological properties, as well as the low-viscosity of the reactive intermediates used to prepare the PUR networks, these biomaterials are potentially useful as injectable, biodegradable bone cements for fracture healing.
1 Communities
1 Members
0 Resources
15 MeSH Terms
Analysis of protein adduction kinetics by quantitative mass spectrometry: competing adduction reactions of glutathione-S-transferase P1-1 with electrophiles.
Orton CR, Liebler DC
(2007) Chem Biol Interact 168: 117-27
MeSH Terms: Biotin, Cysteine, Glutathione S-Transferase pi, Isocyanates, Kinetics, Naphthalenesulfonates, Proteomics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tandem Mass Spectrometry
Show Abstract · Added March 20, 2014
Defining the mechanisms and consequences of protein adduction is crucial to understanding the toxicity of reactive electrophiles. Application of tandem mass spectrometry and data analysis algorithms enables detection and mapping of chemical adducts at the level of amino acid sequence. Nevertheless, detection of adducts does not indicate relative reactivity of different sites. Here, we describe a method to measure the kinetics of competing adduction reactions at different sites on the same protein. Adducts are formed by electrophiles at Cys14 and Cys47 on the metabolic enzyme glutathione-S-transferase P1-1 and modification is accompanied by a loss of enzymatic activity. Relative quantitation of protein adducts was done by tagging N-termini of peptide digests with isotopically labeled phenyl isocyanate and tracking the ratio of light-tagged peptide adducts to heavy-tagged reference samples in liquid chromatography-tandem mass spectrometry analyses using a multiple reaction monitoring method. This approach was used to measure rate constants for adduction at both positions with two different model electrophiles, N-iodoacetyl-N-biotinylhexylenediamine and 1-biotinamido-4-(4'-[maleimidoethyl-cyclohexane]-carboxamido)butane. The results indicate that Cys47 was approximately two- to three-fold more reactive toward both electrophiles than was Cys14. This result was consistent with the relative reactivity of these electrophiles in a complex proteome system and with previously reported trends in reactivity of these sites. Kinetic analyses of protein modification reactions provide a means of evaluating the selectivity of reactive mediators of chemical toxicity.
0 Communities
1 Members
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9 MeSH Terms
Synthesis of biocompatible segmented polyurethanes from aliphatic diisocyanates and diurea diol chain extenders.
Guelcher SA, Gallagher KM, Didier JE, Klinedinst DB, Doctor JS, Goldstein AS, Wilkes GL, Beckman EJ, Hollinger JO
(2005) Acta Biomater 1: 471-84
MeSH Terms: Biocompatible Materials, Cell Culture Techniques, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cross-Linking Reagents, Humans, Isocyanates, Osteosarcoma, Polyurethanes, Tissue Engineering, Urea
Show Abstract · Added February 23, 2016
Many polyurethane elastomers display excellent mechanical properties and adequate biocompatibility. However, many medical-grade polyurethanes are prepared from aromatic diisocyanates and can degrade in vivo to carcinogenic aromatic diamines, although the question of whether the concentrations of these harmful degradation products attain physiologically relevant levels is currently unresolved and strongly debated. It is therefore desirable to synthesize new medical-grade polyurethanes from less toxic aliphatic diisocyanates. In this paper, biocompatible segmented polyurethane elastomers were synthesized from aliphatic diisocyanates (1,4-diisocyanatobutane (BDI) and lysine methyl ester diisocyanate (LDI)), novel diurea diol chain extenders based on tyrosine and tyramine, and a model poly(ethylene glycol) (PEG) diol soft segment. The objectives were to design a hard segment similar in structure to that of MDI-based polyurethanes and also investigate the effects of systematic changes in structure on mechanical and biological properties. The non-branched, symmetric polyurethane prepared from BDI and a tyramine-based chain extender had the highest modulus at 37 degrees C. Introduction of symmetric short-chain branches (SCBs) incorporated in the tyrosine-based chain extender lowered the modulus by an order of magnitude. Polyurethanes prepared from LDI were soft polymers that had a still lower modulus due to the asymmetric SCBs that hindered hard segment packing. Polyurethanes prepared from tyramine and tyrosine chain extenders thermally degraded at temperatures ranging from 110 to 150 degrees C, which are lower than that reported previously for phenyl urethanes. All four polyurethanes supported the attachment, proliferation, and high viability of MG-63 human osteoblast-like cells in vitro. Therefore, the non-cytotoxic chemistry of these polyurethanes make them good candidates for further development as biomedical implants.
1 Communities
1 Members
0 Resources
12 MeSH Terms