Department of Bioengineering and Northeastern University, Boston, Massachusetts, USA.
Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, USA.
Tissue Eng Part A. 2021 Jun;27(11-12):748-760. doi: 10.1089/ten.TEA.2020.0264. Epub 2021 Feb 5.
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°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. Impact statement Hyaluronic 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.
创伤性关节损伤可导致明显的软骨缺损，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，需要采用组织工程方法来填补缺损并促进软骨再生。目前的方法利用侵入性手术从患者体内提取和植入自体软骨细胞；因此，人们对可注射生物材料产生了兴趣，以降低感染风险以及减轻患者的疼痛和不适。在这项研究中，我们设计了仿生的、具有形状记忆特性的透明质酸（HA）基冷冻凝胶支架，在通过注射器注射时可以收缩并恢复形状，从而非侵入性地填充软骨缺损。冷冻凝胶是在-20°C 下用 HA 和甲基丙烯酸缩水甘油酯制成的，具有弹性、大孔和高度互连的网络结构，为注射后的软骨细胞提供了有利的微环境，使其在通过注射器针头注射后仍然能够保持活力和代谢活性。与基于 HA 的水凝胶相比，接种在冷冻凝胶中的软骨细胞在培养 15 天后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，接种了软骨细胞的冷冻凝胶中产生了 II 型胶原蛋白，表明细胞表型得以维持。这些结果表明，接种了软骨细胞的、基于 HA 的、可注射的冷冻凝胶支架具有促进软骨组织再生的潜力，可用于非手术性缺损修复。 影响声明 基于透明质酸的形状记忆冷冻凝胶为软骨细胞的黏附、增殖和基质生物合成提供了有利的微环境，可用于修复软骨缺损。由于其海绵状弹性特性，冷冻凝胶在注射后可以完全恢复其原始形状，而不会影响包裹细胞的代谢或活力。在临床上，它们为通过单次微创注射细胞包封的生物相容性三维支架来填充局灶性软骨缺损提供了机会，这种支架可以恢复到原始结构，以适应缺损的几何形状，并促进基质再生。
