Articular cartilage injury is a widely prevalent condition that leads to a progression of degenerative changes in the joint space. Current treatment methods fall short of long-term tissue repair, and they often miss the complex spatiotemporal microenvironmental cues required for cartilage development, repair, and homeostasis. In response to the fact that cartilage is cell-sparse and has poor inherent regenerative capacity, cell-laden hydrogels have emerged as a suitable approach to cartilage repair. These hydrogel environments are being engineered with microenvironmental cues to promote cell differentiation, matrix synthesis, and construct maturation. Materials designed for the fabrication of these hydrogels can make use of the current understanding of developmental processes, specifically by addressing both the cell-cell and cell-matrix interactions that are required for chondrogenesis, as well as the timing of presentation of such cues.
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CHAPTER 2 RESEARCH OVERVIEW
2.1. SPECIFIC AIMS
Cell-laden hyaluronic acid (HA) hydrogels have been adopted as a promising and extensively studied approach to cartilage repair.1 Advances in the designs of these
hydrogel environments now consider how they can mimic or recapitulate microenvironmental cues that promote relevant cell differentiation, matrix synthesis, and construct maturation. Specifically, these can include interactions between cells and the HA that forms the hydrogel via surface receptors (e.g., CD44), as well as the cell-cell interactions that are essential in the early stages of cartilage tissue development.
The use of HA in these approaches introduces potential biological activity to the hydrogel, such as through binding with the cell-surface receptor CD44 - indeed, this biologically relevant interaction may serve to explain why HA hydrogels are superior to polyethylene glycol (PEG) hydrogels when directly compared toward cartilage tissue engineering with increased extracellular matrix (ECM) synthesis and chondrogenic differentiation of MSCs observed when HA is used.2 However, the modification of HA
through the primary alcohol or carboxylic acid groups is needed to enable crosslinking into hydrogels. These groups may play a role in the interactions with CD44; thus, modification would likely influence the final macromer’s actual biological activity and