Determination of the in vivo degradation mechanism of PEGDA hydrogels.

Determination of the in vivo degradation mechanism of PEGDA hydrogels.
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DOI:
10.1002/jbm.a.35096
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发表时间:
2014-12
影响因子:
4.9
通讯作者:
Cosgriff-Hernandez, E. M.
Cosgriff-Hernandez, E. M.
中科院分区:
工程技术3区
文献类型:
--
作者:
Browning, M. B.;Cereceres, S. N.;Luong, P. T.;Cosgriff-Hernandez, E. M.

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聚乙二醇(PEG)水凝胶是最广泛使用的生物材料系统之一,由于其已建立的生物相容性和高度可调的性能。人们普遍认为,传统的丙烯酸酯衍生的PEG(PEGDA)水凝胶在体内易于缓慢降解,因此不适合长期植入应用。然而,推测观察到的降解是否是由于端基丙烯酸酯水解或醚骨架氧化所致,这两种情况都可能在植入器械的异物反应中发生。PEG双丙烯酰胺(PEGDAA)是一种基于聚醚的水凝胶系统,具有与PEGDA相似的性质,但用酰胺键代替丙烯酸酯。这提供了水解稳定的对照,其可用于分离水解和氧化对PEGDA体内降解的相对贡献。在这里,我们表明PEGDAA水凝胶在大鼠模型中皮下植入12周后保持稳定,而PEGDA水凝胶发生了显著的降解,如溶胀比增加和模量降低所示。由于PEGDA和PEGDAA具有相似的氧化敏感性,这些结果首次证明PEGDA的主要体内降解机制是端基丙烯酸酯的水解。此外,PEGDAA水凝胶在体内的性质的维持表明其适用于长期植入物。这些研究用于阐明关于广泛使用的生物材料系统的关键信息,以允许更好的植入式器械设计,并在需要长期稳定性的应用中为PEGDA提供生物稳定的替代选择。
Poly(ethylene glycol) (PEG) hydrogels are one of the most extensively utilized biomaterials systems due to their established biocompatibility and highly tunable properties. It is widely acknowledged that traditional acrylate-derivatized PEG (PEGDA) hydrogels are susceptible to slow degradation in vivo and are therefore unsuitable for long-term implantable applications. However, there is speculation whether the observed degradation is due to hydrolysis of endgroup acrylate esters or oxidation of the ether backbone both of which are possible in the foreign body response to implanted devices. PEG diacrylamide (PEGDAA) is a polyether-based hydrogel system with similar properties to PEGDA but with amide linkages in place of the acrylate esters. This provides a hydrolytically-stable control that can be used to isolate the relative contributions of hydrolysis and oxidation to the in vivo degradation of PEGDA. Here we show that PEGDAA hydrogels remained stable over 12 weeks of subcutaneous implantation in a rat model while PEGDA hydrogels underwent significant degradation as indicated by both increased swelling ratio and decreased modulus. As PEGDA and PEGDAA have similar susceptibility to oxidation, these results demonstrate for the first time that the primary in vivo degradation mechanism of PEGDA is hydrolysis of the endgroup acrylate ester. Additionally, the maintenance of PEGDAA hydrogel properties in vivo indicates their suitability for long-term implants. These studies serve to elucidate key information about a widely used biomaterial system to allow for better implantable device design and to provide a biostable replacement option for PEGDA in applications that require long-term stability.
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