Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843, USA.
Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton, BME 3.503D, 1 University Station, C0800, Austin, TX, 78712, USA.
Ann Biomed Eng. 2020 Mar;48(3):953-967. doi: 10.1007/s10439-019-02271-8. Epub 2019 May 28.
Resorbable hydrogels have numerous potential applications in tissue engineering and drug delivery due to their highly tunable properties and soft tissue-like mechanical properties. The incorporation of esters into the backbone of poly(ethylene glycol) hydrogels has been used to develop libraries of hydrogels with tunable degradation rates. However, these synthetic strategies used to increase degradation rate often result in undesired changes in the hydrogel physical properties such as matrix modulus or swelling. In an effort to decouple degradation rate from other hydrogel properties, we inserted thio-β esters into the poly(ethylene glycol)-diacrylate backbone to introduce labile bonds without changing macromer molecular weight. This allowed the number of hydrolytically labile thio-β esters to be controlled through changing the ratios of this modified macromer to the original macromer without affecting network properties. The retention of hydrogel properties at different macromer ratios was confirmed by measuring gel fraction, swelling ratio, and compressive modulus. The tunable degradation profiles were characterized both in vitro and in vivo. Following confirmation of cytocompatibility after exposure to the hydrogel degradation products, the in vivo host response was evaluated in comparison to medical grade silicone. Collectively, this work demonstrates the utility and tunability of these hydrolytically degradable hydrogels for a wide variety of tissue engineering applications.
可吸收水凝胶因其具有高度可调的特性和类似软组织的机械特性，在组织工程和药物输送方面具有众多潜在应用。在聚乙二醇水凝胶的主链中引入酯基已被用于开发具有可调降解率的水凝胶库。然而，这些用于提高降解率的合成策略通常会导致水凝胶物理性质（如基质模量或溶胀）的不期望变化。为了使降解率与其他水凝胶性质解耦，我们将硫代β酯插入聚乙二醇二丙烯酸酯主链中，以引入不稳定的键，而不改变大分子单体的分子量。这使得通过改变这种改性大分子单体与原始大分子单体的比例，可以控制水解不稳定的硫代β酯的数量，而不影响网络性质。通过测量凝胶分数、溶胀比和压缩模量来确认不同大分子单体比例下水凝胶性质的保留。可调节的降解曲线在体外和体内进行了表征。在确认暴露于水凝胶降解产物后的细胞相容性后，将体内宿主反应与医用级硅胶进行了比较。总的来说，这项工作证明了这些可水解降解水凝胶在各种组织工程应用中的实用性和可调性。
