Abstract
Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.
Highlights
Osteoarthritis (OA) affects more than 10% of men and 18% of women worldwide and places an enormous socio-economic burden on health care systems worldwide, with the number of joint replacement surgeries projected to increase steadily [1,2,3]
Current research focuses on the use of these three-dimensional hydrogels, which mimic the extracellular matrix (ECM) of hyaline cartilage to further optimize the treatment of cartilage defects
Natural hydrogels can be further separated into polysaccharide-based hydrogels formed from agarose (AG), alginate (AL), glycosaminoglycans (GAGs), and chitosan (CH), as well as protein-based hydrogels formed from collagen (COL), elastin (EL), gelatin (GEL), or other polymers [26]
Summary
Osteoarthritis (OA) affects more than 10% of men and 18% of women worldwide and places an enormous socio-economic burden on health care systems worldwide, with the number of joint replacement surgeries projected to increase steadily [1,2,3]. Damage to hyaline cartilage or osteochondral lesions naturally results in lasting defects or the formation of inferior fibrocartilage, which is why surgical and regenerative treatment methods for cartilage repair have gained growing interest [4,5]. Tissue engineering combines the use of growth factors, gene transfer, and biomaterials to optimize chondrogenic differentiation and maintenance of a chondrogenic phenotype in seeded cells. Cell-based approaches, such as tissue engineering (TE), combine the use of chondrogenic growth factors, cells, and functional scaffolds to further optimize the treatment of cartilage defects (Figure 1) [6]. MSCs carry a characteristic set of surface markers, grow plastic adherent, can be differentiated toward the osteogenic, adipogenic, and chondrogenic lineage in vitro, and have been shown to reside in various, accessible adult and human fetal tissues [10,11]. Despite good in vitro and in vivo data, limitations to the use of MSCs include loss of transplanted cells upon transplantation, insufficient chondrogenic differentiation, osteogenic de-differentiation, chondrogenic hypertrophy, or failed integration in targeted defects [4,13]
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