Enhanced regeneration of osteochondral defects by using an aggrecanase-1 responsively degradable and N-cadherin mimetic peptide-conjugated hydrogel loaded with BMSCs
Enhanced regeneration of osteochondral defects by using an aggrecanase-1 responsively degradable and N-cadherin mimetic peptide-conjugated hydrogel loaded with BMSCs
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使用负载 BMSC 的聚集蛋白聚糖酶 1 响应性可降解和 N-钙粘蛋白模拟肽缀合水凝胶增强骨软骨缺损的再生
DOI：
10.1039/d0bm00068j
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发表时间：
2020
影响因子：
6.6
通讯作者：
Gao Changyou
中科院分区：
文献类型：
--
作者：
Feng Xue;Zhou Tong;Xu Peifang;Ye Juan;Gou Zhongru;Gao Changyou
由于关节软骨自身修复能力差，软骨或骨软骨损伤难以恢复。在这项研究中，N-钙粘蛋白模拟肽序列HAVDIGGGC（HAV）被缀合以直接细胞-细胞相互作用，并且聚集蛋白聚糖酶-1可切割肽序列CRDTEGE-ARGSVIDRC（ACPep）被用于交联超支化的基于PEG的多丙烯酸酯聚合物（HBPEG）与半胱胺修饰的硫酸软骨素（Cys-CS），获得聚集蛋白聚糖酶-1响应性可降解的HAV缀合的水凝胶（（HAV-HBPEG）-CS-ACPep）。还制备了没有HAV基序的HBPEG-CS-ACPep水凝胶。这两种水凝胶在冻干后表现出相似的平衡溶胀比、弹性模量和孔径，表明共轭HAV对水凝胶的交联网络和机械性能的影响可以忽略不计。在PBS、聚集蛋白聚糖酶-1（ADAMTS 4）和胰蛋白酶中降解后，HBPEG-CS-ACPep水凝胶表现出显著降低的弹性模量，当在酶溶液中孵育时具有低得多的值。两种水凝胶均能维持包封的骨髓间充质干细胞（BMSCs）的活力，其中（HAV-HBPEG）-CS-ACPep水凝胶更能促进细胞间的相互作用。植入兔骨软骨缺损18周后，两组载细胞水凝胶组的修复效果均优于空白对照组。此外，（HAV-HBPEG）-CS-ACPep/BMSCs水凝胶组形成透明软骨，而HBPEG-CS-ACPep/BMSCs水凝胶组形成透明软骨和纤维软骨的混合体。
Due to the poor self-repair capabilities of articular cartilage, chondral or osteochondral injuries are difficult to be recovered. In this study, an N-cadherin mimetic peptide sequence HAVDIGGGC (HAV) was conjugated to direct cell–cell interactions, and an aggrecanase-1 cleavable peptide sequence CRDTEGE-ARGSVIDRC (ACpep) was used to crosslink hyperbranched PEG-based multi-acrylate polymer (HBPEG) with cysteamine-modified chondroitin sulfate (Cys-CS), obtaining an aggrecanase-1 responsively degradable and HAV-conjugated hydrogel ((HAV-HBPEG)-CS-ACpep). A HBPEG-CS-ACpep hydrogel without the HAV motif was also prepared. The two hydrogels exhibited similar equilibrium swelling ratios, elastic moduli and pore sizes after lyophilization, indicating the negligible influence of conjugated HAV on the crosslinking networks and mechanical properties of the hydrogels. After being degraded in PBS, aggrecanase-1 (ADAMTS4) and trypsin, the HBPEG-CS-ACpep hydrogel exhibited significantly decreased elastic moduli with a much lower value when incubated in enzyme solutions. The two hydrogels could maintain the viability of encapsulated bone marrow-derived mesenchymal stem cells (BMSCs), and the (HAV-HBPEG)-CS-ACpep hydrogel better promoted the cell–cell interactions. After being implanted into osteochondral defects in rabbits for 18 weeks, the two cell-laden hydrogel groups achieved better repair effects than the blank control group. Moreover, hyaline cartilage was formed in the (HAV-HBPEG)-CS-ACpep/BMSCs hydrogel group, while a hybrid of hyaline cartilage and fibrocartilage was found in the HBPEG-CS-ACpep/BMSCs hydrogel group.