Hyaluronic Acid-Based Shape-Memory Cryogel Scaffolds for Focal Cartilage Defect Repair
Hyaluronic Acid-Based Shape-Memory Cryogel Scaffolds for Focal Cartilage Defect Repair
复制标题
DOI：
10.1089/ten.tea.2020.0264
复制
发表时间：
2021-02-05
影响因子：
4.1
通讯作者：
Bajpayee, Ambika G.
中科院分区：
文献类型：
--
作者：
He, Tengfei;Li, Boting;Bajpayee, Ambika G.
影响声明基于透明质酸的形状记忆冷冻凝胶为软骨细胞粘附、增殖和基质生物合成提供了有利的微环境，用于修复软骨缺损。由于其海绵状的弹性特性，冷冻凝胶可以在注射后完全恢复其原始形状，同时不影响封装细胞的代谢或活力。在临床上，它们提供了一个机会，通过使用一个单一的，微创注射的细胞封装的生物相容性三维支架，可以返回到其原始结构，以适应缺陷的几何形状，并使基质再生局灶性软骨缺损。创伤性关节损伤可能会导致显着的软骨缺损，这可能会大大增加骨关节炎发展的风险。由于无血管软骨的自我修复能力有限，需要组织工程方法来填充缺损并促进软骨再生。目前的方法利用侵入性外科手术来提取和植入自体软骨细胞;因此，可注射生物材料已获得兴趣，以最大限度地减少感染风险以及患者疼痛和不适。在这项研究中，我们设计了仿生的，基于透明质酸（HA）的冷冻凝胶支架，这些支架具有形状记忆特性，因为它们在注射器注射后收缩并恢复形状，以非侵入性地填充软骨缺损。这些冷冻凝胶由HA和甲基丙烯酸缩水甘油酯在-20摄氏度下制成，形成了弹性、大孔和高度互连的网络，为软骨细胞在通过注射器针头注射后保持活力和代谢活性提供了有利的微环境。与HA基水凝胶相比，软骨细胞接种在冷冻凝胶内并培养15天，表现出增强的细胞增殖、代谢和软骨细胞外基质糖胺聚糖的产生。此外，免疫组织化学染色显示软骨细胞接种的冷冻凝胶产生II型胶原，表明细胞表型的维持。这些结果表明，软骨细胞接种的、基于HA的、可注射的冷冻凝胶支架具有促进软骨组织再生以进行非手术侵入性缺陷修复的潜力。
Impact statementHyaluronic acid-based shape-memory cryogels provide a conducive microenvironment for chondrocyte adhesion, proliferation, and matrix biosynthesis for use in repair of cartilage defects. Due to their sponge-like elastic properties, cryogels can fully recover their original shape back after injection while not impacting metabolism or viability of encapsulated cells. Clinically, they provide an opportunity for filling focal cartilage defects by using a single, minimally invasive injection of a cell encapsulating biocompatible three-dimensional scaffold that can return to its original structure to fit the defect geometry and enable matrix regeneration.Traumatic joint injuries can result in significant cartilage defects, which can greatly increase the risk of osteoarthritis development. Due to the limited self-healing capacity of avascular cartilage, tissue engineering approaches are required for filling defects and promoting cartilage regeneration. Current approaches utilize invasive surgical procedures for extraction and implantation of autologous chondrocytes; therefore, injectable biomaterials have gained interest to minimize the risk of infection as well as patient pain and discomfort. In this study, we engineered biomimetic, hyaluronic acid (HA)-based cryogel scaffolds that possess shape-memory properties as they contract and regain their shape after syringe injection to noninvasively fill cartilage defects. The cryogels, fabricated with HA and glycidyl methacrylate at -20 degrees C, resulted in an elastic, macroporous, and highly interconnected network that provided a conducive microenvironment for chondrocytes to remain viable and metabolically active after injection through a syringe needle. Chondrocytes seeded within cryogels and cultured for 15 days exhibited enhanced cell proliferation, metabolism, and production of cartilage extracellular matrix glycosaminoglycans compared with HA-based hydrogels. Furthermore, immunohistochemical staining revealed production of collagen type II from chondrocyte-seeded cryogels, indicating the maintenance of cell phenotype. These results demonstrate the potential of chondrocyte-seeded, HA-based, injectable cryogel scaffolds to promote regeneration of cartilage tissue for nonsurgically invasive defect repair.