Hyaluronic acid-based shape-memory cryogel scaffolds for focal cartilage defect repair.

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 in order to minimize the risk of infection as well as patient pain and discomfort. Here, we engineered biomimetic, hyaluronic acid (HA)-based cryogel scaffolds that possess shape-memory properties as they contract and regain their shape following syringe injection to non-invasively 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 following 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 to in 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 non-surgically invasive defect repair.