Bioactive Phenylboronic Acid‐Functionalized Hyaluronic Acid Hydrogels Induce Chondro‐Aggregates and Promote Chondrocyte Phenotype

Abstract

Hydrogels are extensively investigated as biomimetic extracellular matrix (ECM) scaffolds in tissue engineering. The physiological properties of ECM affect cellular behaviors, which is an inspiration for cell‐based therapies. Photocurable hyaluronic acid (HA) hydrogel (AHAMA‐PBA) modified with 3‐aminophenylboronic acid, sodium periodate, and methacrylic anhydride simultaneously is constructed in this study. Chondrocytes are then cultured on the surface of the hydrogels to evaluate the effect of the physicochemical properties of the hydrogels on modulating cellular behaviors. Cell viability assays demonstrate that the hydrogel is non‐toxic to chondrocytes. The existence of phenylboronic acid (PBA) moieties enhances the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia. RT‐PCR indicates that the gene expression levels of type II collagen, Aggrecan, and Sox9 are significantly up‐regulated in chondrocytes cultured on hydrogels. Moreover, the mechanical properties of the hydrogels have a significant effect on the cell phenotype, with soft gels (≈2 kPa) promoting chondrocytes to exhibit a hyaline phenotype. Overall, PBA‐functionalized HA hydrogel with low stiffness exhibits the best effect on promoting the chondrocyte phenotype, which is a promising biomaterial for cartilage regeneration.

Construction of a Decellularized Multicomponent Extracellular Matrix Interpenetrating Network Scaffold by Gelatin Microporous Hydrogel 3D Cell Culture System

“…This library, specifically created for soft hydrogels (E = 10-50 kPa), can be employed to encapsulate various cells, such as human chondrocytes. [56] Low-stiffness hyaluronic acid hydrogels modified with phenylboronic acid (E < 5 kPa) promote a transparent phenotype in chondrocytes, [57] while a stiffer matrix (E > 20 kPa) may be more suitable for the deposition of cartilaginous matrix based on chondrocytes. [58,59] Polyethylene glycol hydrogels, simulating a gradient stiffness characteristic of cartilage (2-60 kPa), can induce specific responses in chondrocytes, promoting ECM deposition in simulated cartilage-like tissue.…”