Abstract
Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.
Highlights
Articular cartilage is a specialized connective tissue with limited self-repair due to its avascular nature and limited cellularity
We demonstrated that CH nanoforms, in particular chitin nanocrystals (CHNCs), provide mechanical and topological cues to support the growth of human adipose tissue-derived mesenchymal stem cells (hASCs) in CS-based biomaterials for Tissue engineering (TE) [22]
Spheroids cultured in chondrogenic induction medium (CIM) maintained the typical compact physical structure of chondrospheroids for the length of the experiment (21 days; Figure 5). These results suggest that the 3D CS/CHNC scaffold is suitable for supporting hASC spheroids differentiating as chondrification centers
Summary
Articular cartilage is a specialized connective tissue with limited self-repair due to its avascular nature and limited cellularity. The damage and loss of cartilage tissue leads to the progressive remodeling of the subchondral bone leading to osteoarthritis [1], which is the most common and prevalent form of joint disease. The inability of cartilage to repair itself, together with the limited success of current therapies, call for the development of new therapeutic strategies for restoring the functional properties of this type of tissue [2]. Tissue engineering (TE) has undergone a major revolution over the past decade with the development of newly in vitro-formed tissue-material constructs, which exhibit similar biological and mechanical characteristics to those of mature cartilage [3]. There are specific limitations associated with the use of these cells, namely, cell availability, as well as reduced expansion capacity in vitro and a tendency towards the loss of the differentiated phenotype [4]
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