Alginate hydrogels modified with low molecular weight hyaluronate for cartilage regeneration

Alginate is a typical biomaterial that forms hydrogels in the presence of calcium ions and has often been utilized in tissue engineering approaches. However, it lacks biofunctionality in the form of interactions with cells and proteins. Hyaluronate, a main component of glycosaminoglycans, provides CD44-specific interactions with chondrocytes but typically requires chemical cross-linking agents to fabricate hydrogels, which may cause unexpected side effects in the body. In this study, we propose the design and fabrication of a hybrid structure of alginate and hyaluronate useful for cartilage regeneration. Alginate was used as a backbone, and hyaluronate with a low molecular weight was introduced to the backbone to fabricate alginate-hyaluronate hybrid coupled by ethylenediamine. We hypothesized that alginate-hyaluronate hybrid (AH) could maintain its ability to form gels in the presence of calcium ions and could be useful for cartilage regeneration as an injectable system. Characteristics of AH hydrogels containing various composition ratios of hyaluronate to alginate were investigated, and the chondrogenic potential of ATDC5 cells encapsulated within AH hydrogels was evaluated in vitro. Consequently, AH hydrogels having a defined polymer composition and mechanical stiffness were useful to successfully regulate chondrogenic differentiation and to maintain the chondrocytic cell phenotype, which may lead to many useful applications in cartilage regeneration.