Browning M B, Cereceres S N, Luong P T, Cosgriff-Hernandez E M
Department of Biomedical Engineering, Texas A&M University, College Station, Texas, 77843-3120.
J Biomed Mater Res A. 2014 Dec;102(12):4244-51. doi: 10.1002/jbm.a.35096. Epub 2014 Feb 13.
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 esters. 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.
聚乙二醇（PEG）水凝胶是应用最为广泛的生物材料系统之一，因其具有公认的生物相容性和高度可调节的特性。众所周知，传统的丙烯酸酯衍生化PEG（PEGDA）水凝胶在体内易发生缓慢降解，因此不适用于长期可植入应用。然而，目前尚不清楚观察到的降解是由于端基丙烯酸酯的水解还是醚主链的氧化，这两种情况在植入装置的异物反应中都有可能发生。PEG二丙烯酰胺（PEGDAA）是一种基于聚醚的水凝胶系统，其性质与PEGDA相似，但用酰胺键取代了丙烯酸酯。这提供了一种水解稳定的对照物，可用于分离水解和氧化对PEGDA体内降解的相对贡献。在此，我们表明，在大鼠模型中皮下植入12周后，PEGDAA水凝胶保持稳定，而PEGDA水凝胶则发生了显著降解，表现为溶胀率增加和模量降低。由于PEGDA和PEGDAA对氧化的敏感性相似，这些结果首次证明PEGDA在体内的主要降解机制是端基丙烯酸酯的水解。此外，PEGDAA水凝胶在体内性质的维持表明它们适用于长期植入物。这些研究有助于阐明关于一种广泛使用的生物材料系统的关键信息，以便进行更好的可植入装置设计，并为需要长期稳定性的应用提供一种生物稳定的PEGDA替代物。
