An enzyme-sensitive PEG hydrogel based on aggrecan catabolism for cartilage tissue engineering.
An enzyme-sensitive PEG hydrogel based on aggrecan catabolism for cartilage tissue engineering.
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DOI：
10.1002/adhm.201400277
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发表时间：
2015-02-18
影响因子：
10
通讯作者：
Bryant SJ
中科院分区：
文献类型：
--
作者：
Skaalure SC;Chu S;Bryant SJ
介绍了一种基于可光点击的硫醇烯PEG水凝胶的软骨特异性可降解水凝胶。水凝胶交联由肽CRDTEGE-ARGSVIDRC组成，该肽来源于聚集蛋白聚糖中的聚集蛋白聚糖酶可裂解位点。通过包封来自不同细胞来源的牛软骨细胞（未成熟（幼年）和成熟（成年）供体以及用促炎性脂多糖（LPS）刺激的成年细胞）并培养12周来评估这种新的水凝胶在软骨组织工程中的用途。无论细胞来源如何，到12周时观察到压缩模量降低两倍，但没有显著的水凝胶溶胀，表明体积降解有限。对于幼年细胞，观察到富含聚集蛋白聚糖和胶原蛋白II的连接基质，但胶原蛋白I和X极少。对于成体细胞，沉积较少的基质，但质量相似。聚集蛋白聚糖酶活性升高，但不加速本体水凝胶降解。LPS进一步降低基质产生，但不影响聚集蛋白聚糖酶活性。相比之下，不可降解水凝胶中的基质沉积由聚集蛋白聚糖和胶原蛋白I、II和X组成，表明软骨肥大。最后，通过聚集蛋白聚糖酶敏感性水凝胶未观察到软骨细胞中的炎症反应。总的来说，我们证明了这种新的聚集蛋白聚糖酶敏感的水凝胶，它是由软骨细胞降解，并促进透明样工程软骨，是有希望的软骨再生。
A new cartilage-specific degradable hydrogel based on photoclickable thiol-ene PEG hydrogels is presented. The hydrogel crosslinks are composed of the peptide, CRDTEGE-ARGSVIDRC, derived from the aggrecanase-cleavable site in aggrecan. This new hydrogel is evaluated for use in cartilage tissue engineering by encapsulating bovine chondrocytes from different cell sources (skeletally immature (juvenile) and mature (adult) donors and adult cells stimulated with pro-inflammatory lipopolysaccharide (LPS)) and culturing for 12 weeks. Regardless of cell source, a two-fold decrease in compressive modulus is observed by 12 weeks, but without significant hydrogel swelling indicating limited bulk degradation. For juvenile cells, a connected matrix rich in aggrecan and collagen II, but minimal collagens I and X is observed. For adult cells, less matrix, but similar quality, is deposited. Aggrecanase activity is elevated, although without accelerating bulk hydrogel degradation. LPS further decreased matrix production, but did not affect aggrecanase activity. In contrast, matrix deposition in the non-degradable hydrogels consisted of aggrecan and collagens I, II and X, indicative of hypertrophic cartilage. Lastly, no inflammatory response in chondrocytes is observed by the aggrecanase-sensitive hydrogels. Overall, we demonstrate that this new aggrecanase-sensitive hydrogel, which is degradable by chondrocytes and promotes a hyaline-like engineered cartilage, is promising for cartilage regeneration.