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首页> 外文期刊>Acta biomaterialia >Engineering endostatin-expressing cartilaginous constructs using injectable biopolymer hydrogels
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Engineering endostatin-expressing cartilaginous constructs using injectable biopolymer hydrogels

机译：使用可注射生物聚合物水凝胶工程化表达内皮抑素的软骨构建体

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The release of an anti-angiogenic agent, such as type XVIII/endostatin, from an implantable scaffold may be of benefit in the repair of articular cartilage. The objectives of this study are to develop an injectable mesenchymal stem cell (MSC)-incorporating collagen-based hydrogel capable of undergoing covalent cross-linking in vivo and overexpressing endostatin using nonviral transfection, and to investigate methods for the retention of the endostatin protein within the scaffolds. The effects of different cross-linking agents (genipin, transglutaminase-2, and microbial transglutaminase) and different binding molecules for endostatin retention (heparin, heparan sulfate, and chondroitin sulfate) are evaluated. Cartilaginous constructs that overexpress endostatin for 3 weeks are successfully engineered. Most of the endostatin is released into the surrounding media and is not retained within the constructs. The presence of two common basement membrane molecules, laminin and type IV collagen, which have been reported in developing and mature articular cartilage and are generally associated with type XVIII collagen in vivo, is also observed in the engineered cartilaginous constructs. Endostatin-producing cartilaginous constructs can be formulated by growing nonvirally transfected mesenchymal stem cells in collagen gels covalently cross-linked using genipin, transglutaminase-2, and microbial transglutaminase. These constructs warrant further investigation for cartilage repair procedures. The novel finding of laminin and type IV collagen in the engineered cartilage constructs may be of importance for future work toward understanding the role of basement membrane molecules in chondrogenesis and in the physiology and pathology of articular cartilage.
机译：从可植入的支架中释放抗血管生成剂，例如XVIII /内皮抑素，可能有益于关节软骨的修复。这项研究的目的是开发一种可注射的间充质干细胞（MSC）-基于胶原蛋白的水凝胶，该凝胶能够在体内进行共价交联并使用非病毒转染来过度表达内皮抑素，并研究将内皮抑素蛋白保留在体内的方法脚手架。评估了不同交联剂（genipin，transglutaminase-2和微生物转谷氨酰胺酶）和不同结合分子对内皮抑素保留（肝素，硫酸乙酰肝素和硫酸软骨素）的影响。成功设计了过表达内皮抑素3周的软骨构建体。大多数内皮抑素释放到周围介质中，并且不保留在构建体中。在工程化的软骨构造中也观察到了两种常见的基底膜分子，层粘连蛋白和IV型胶原蛋白的存在，这些分子已在发育和成熟的关节软骨中被报道，并且通常与体内的XVIII型胶原蛋白相关。可以通过使用genipin，transglutaminase-2和微生物transglutaminase在共价交联的胶原凝胶中培养非病毒转染的间充质干细胞，从而配制产生内皮抑素的软骨构建体。这些结构值得进一步研究软骨修复程序。在工程化的软骨构造中层粘连蛋白和IV型胶原蛋白的新发现可能对理解基底膜分子在软骨形成以及关节软骨的生理和病理学中的作用的未来工作很重要。

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