Lillian Nanney
Last active: 1/20/2015

Characterization of the degradation mechanisms of lysine-derived aliphatic poly(ester urethane) scaffolds.

Hafeman AE, Zienkiewicz KJ, Zachman AL, Sung HJ, Nanney LB, Davidson JM, Guelcher SA
Biomaterials. 2011 32 (2): 419-29

PMID: 20864156 · PMCID: PMC2997347 · DOI:10.1016/j.biomaterials.2010.08.108

Characterization of the degradation mechanism of polymeric scaffolds and delivery systems for regenerative medicine is essential to assess their clinical applicability. Key performance criteria include induction of a minimal, transient inflammatory response and controlled degradation to soluble non-cytotoxic breakdown products that are cleared from the body by physiological processes. Scaffolds fabricated from biodegradable poly(ester urethane)s (PEURs) undergo controlled degradation to non-cytotoxic breakdown products and support the ingrowth of new tissue in preclinical models of tissue regeneration. While previous studies have shown that PEUR scaffolds prepared from lysine-derived polyisocyanates degrade faster under in vivo compared to in vitro conditions, the degradation mechanism is not well understood. In this study, we have shown that PEUR scaffolds prepared from lysine triisocyanate (LTI) or a trimer of hexamethylene diisocyanate (HDIt) undergo hydrolytic, esterolytic, and oxidative degradation. Hydrolysis of ester bonds to yield α-hydroxy acids is the dominant mechanism in buffer, and esterolytic media modestly increase the degradation rate. While HDIt scaffolds show a modest (<20%) increase in degradation rate in oxidative medium, LTI scaffolds degrade six times faster in oxidative medium. Furthermore, the in vitro rate of degradation of LTI scaffolds in oxidative medium approximates the in vivo rate in rat excisional wounds, and histological sections show macrophages expressing myeloperoxidase at the material surface. While recent preclinical studies have underscored the potential of injectable PEUR scaffolds and delivery systems for tissue regeneration, this promising class of biomaterials has a limited regulatory history. Elucidation of the macrophage-mediated oxidative mechanism by which LTI scaffolds degrade in vivo provides key insights into the ultimate fate of these materials when injected into the body.

Copyright © 2010 Elsevier Ltd. All rights reserved.

MeSH Terms (16)

Animals Biocompatible Materials Cell Line Lysine Male Materials Testing Mechanics Mice Microscopy, Electron, Scanning Polyesters Polyurethanes Rats Rats, Sprague-Dawley Tissue Engineering Tissue Scaffolds Wound Healing

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