In addition to being a major constituent of the extracellular matrix (ECM), hyaluronic acid (HA) plays essential roles as a structural component and a signaling molecule in various tissues, including articular cartilage. Its physiological functions, as well as its desirable properties in terms of biocompatibility, biodegradability, nontoxicity, and non-immunogenicity set it forth as a major element in biomedicine. Among its several applications, HA has been used in the preparation of hydrogels mainly via chemical modifications. These modifications are aimed at enhancing its properties, and therefore, broadening its utility, which made HA-based hydrogels useful in applications such as tissue engineering and drug delivery.
Bone and cartilage tissue engineering are the fields in which HA-based hydrogels are most extensively applied. These hydrogels serve as temporary scaffolds that support cells and guide the regeneration of functional tissues. However, the ideal HA hydrogel formulation for articular cartilage tissue engineering has still not been resolved, and this explains why the optimization of biomaterials for cartilage regeneration is in a state of continuous activity and advancement.
To test the effects of the functionalization of HA on chondrogenesis, a group of researchers from China recently optimized HA by three ways: first, synthesizing a methacrylated hyaluronic acid (MeHA); second, integrating two biomimetic peptides arginine-glycine-aspartate (RGD) and histidine-alanine-valine (HAV); and third, introducing kartogenin (KGN)-encapsulated poly(lactic-co-glycolic acid) (PLGA) microspheres (KGN@PM). Methacrylation can increase mechanical stiffness and long-term stability, whereas RGD peptide, HAV peptide, and KGN are suggested to promote chondrogenesis and maintain the phenotype of chondrocytes.
After synthesizing the functionalized HA hydrogel, researchers combined it with human mesenchymal stem cells (hMSCs), and then evaluated the whole system on several levels using in vitro studies (via 2D and 3D cell cultures) and preclinical in vivo studies (using nude mice models). Results showed that this hydrogel system has the potential to enhance proliferation, adhesion, condensation, and chondrogenic differentiation of hMSCs during neo-chondrogenesis, as presented in Scheme 1 (the graphical abstract of the original article) below. These preliminary results suggest that such a system can be used in cartilage tissue engineering, as well as in other clinical applications, including 3D-printed gel scaffolds and microfluidic technologies.
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Teng, B., Zhang, S., Pan, J., Zeng, Z., Chen, Y., Hei, Y., Fu, X., Li, Q., Ma, M., Sui, Y., & Wei, S. (2021).
A chondrogenesis induction system based on a functionalized hyaluronic acid hydrogel sequentially promoting hMSC proliferation, condensation, differentiation, and matrix deposition. Acta biomaterialia, 122, 145–159.