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首页> 外文期刊>Biomaterials Science >Evaluation of MMP substrate concentration and specificity for neovascularization of hydrogel scaffolds
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Evaluation of MMP substrate concentration and specificity for neovascularization of hydrogel scaffolds

机译：评估MMP底物浓度和水凝胶支架新血管形成的特异性

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Controlled vascular response in scaffolds following implantation remains a significant clinical challenge. A critical biomaterial design criterion is the synchronization of the rates of scaffold degradation and vascularized tissue formation. Matrix metalloproteinases (MMPs) are key enzymes that regulate neovascularization and extracellular matrix remodelling. Synthetic protease-sensitive hydrogels offer controllable environments for investigating the role of matrix degradation on neovascularization. In this study, PEG hydrogels containing MMP-sensitive peptides with increased catalytic activity for MMPs expressed during neovascularization were investigated. Scaffolds were functionalized with MMP-2-, MMP-14- or general collagenase-sensitive peptides and with varying peptide concentration using crosslinkers containing one (SSite) or multiple (TSite) repeats of each protease-sensitive sequence. Increasing peptide concentration enhanced the degradation kinetics of scaffolds functionalized with MMP-specific sequences while 80% of the collagenase-sensitive scaffolds remained upon exposure to MMP-2 and MMP-14. In vitro neovascularization was consistent with in vivo tissue invasion with significantly increased invasion occurring within SSite MMP-specific as compared to collagenase-sensitive hydrogels and with further invasion in TSite as compared to SSite hydrogels regardless of peptide specificity. All scaffolds supported in vivo neovascularization; however, this was not dependent on peptide specificity. These findings demonstrate that peptide concentration and specificity regulate in vivo scaffold degradation, neovascularization and matrix remodelling.
机译：植入后支架中受控的血管反应仍然是一项重大的临床挑战。关键的生物材料设计标准是支架降解和血管化组织形成的速率同步。基质金属蛋白酶（MMP）是调节新血管形成和细胞外基质重塑的关键酶。合成蛋白酶敏感性水凝胶为研究基质降解在新血管形成中的作用提供了可控的环境。在这项研究中，研究了含有MMP敏感肽的PEG水凝胶，该肽对新血管形成过程中表达的MMP具有增强的催化活性。使用包含每种蛋白酶敏感序列的一个（SSite）或多个（TSite）重复序列的交联剂，用MMP-2-，MMP-14-或一般胶原酶敏感肽对肽进行功能化。肽浓度的增加增强了被MMP特异性序列功能化的支架的降解动力学，而80％的胶原酶敏感支架在暴露于MMP-2和MMP-14后仍然保留。与胶原酶敏感的水凝胶相比，体外新血管形成与体内组织浸润相一致，与胶原酶敏感的水凝胶相比，SSite MMP特异性内发生的浸润显着增加，而与SSite水凝胶相比，无论肽特异性如何，TSite中的浸润均进一步。所有支架均支持体内新血管形成;但是，这不取决于肽的特异性。这些发现表明肽的浓度和特异性调节体内支架降解，新血管形成和基质重塑。

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