This work raises the potential of utilizing stem cells to catalyze cartilage regeneration by a minimal number of neonatal chondrocytes via controlling cell distribution in 3D matrices, and may solve the challenge of scarce donor availability associated with cell-based therapy. Cartilage loss is a leading cause of disability among adults and represents a huge socio-economical burden. Allogeneic neonatal articular chondrocytes (NChons) is a promising cell source for cartilage regeneration because these cells are highly proliferative, immune-privileged, and readily produce abundant cartilage matrix. However, scarce donor availability for NChons greatly hinders their broad clinical application. Besides their ability to differentiate into different tissue types, stem cells may contribute to tissue regeneration through the secretion of paracrine factors. Here we examined the potential for using a minimal number of NChons to catalyze cartilage tissue formation by co-culturing them with adipose-derived stem cells (ADSCs) in 3D biomimetic hydrogels.Summary Statement
Introduction
We have developed 3D combinatorial hydrogels containing cartilage extracellular matrix (ECM) proteins for modulating chondrogenesis of adipose-derived stromal cells. Our platform allows independently tunable biochemical and mechanical properties, which may provide a valuable tool for elucidating how ECM biochemical cues interact with matrix stiffness to regulate stem cell chondrogenesis. Adipose-derived stromal cells (ADSC) hold great promise for cartilage repair given their relative abundance and ease of isolation. Biomaterials can serve as artificial niche to direct chondrogenesis of ADSCs, and extracellular matrix (ECM) protein-based scaffolds are highly biomimetic. However, incorporating ECM molecules into hydrogel network often lead to simultaneous changes in both biochemical ligand density and matrix stiffness. This makes it difficult to understand how various niche signals interact together to regulate ADSC fate. To overcome these limitations, the goal of this study is to develop an ECM-containing hydrogel platform with independently tunable biochemical and mechanical cues for modulating ADSC chondrogenesis in 3D. We hypothesise that decreasing the degree of crosslinking of ECM molecules may allow their incorporation without affecting the matrix stiffness. The effects of interactive signaling between ECM molecules and matrix stiffness on ADSC chondrogenesis in 3D was then examined using this platformSummary Statement
Introduction
