Synthesis and Engineering of Hyaluronic Acid-Gelatin Hydrogels with Improved Cellular Attachment and Growth

Injectable hydrogels are promising materials for cartilage regeneration in tissue engineering due to their tunable crosslinking rates, mechanical properties, and biodegradation profiles. This study investigates the chondrogenic potential of hyaluronic acid (HA) hydrogels crosslinked via tyramine (TA) moieties, with and without gelatin modified with TA (Gel-TA). Incorporating Gel-TA improved cell viability, spreading, and cartilage matrix deposition, particularly in medium and high molecular weight (MMW and HMW) HA-TA/Gel-TA hydrogels. Although the hydrogels’ molecular weight did not significantly alter stiffness, MMW and HMW HA-TA/Gel-TA formulations exhibited enhanced functional properties such as slower degradation and superior cartilage matrix deposition. These attributes, coupled with Gel-TA’s effects, underscore the importance of both molecular weight and biofunctional components in hydrogel design for cartilage regeneration. While low molecular weight (LMW) HA-TA hydrogels offered excellent injectability and supported high cell viability, they degraded rapidly and exhibited reduced cartilage matrix formation. Gel-TA enhanced cell adhesion and spreading by providing integrin-binding sites and promoted collagen type II deposition, crucial for cartilage regeneration. Moreover, the increased stiffness of MMW and HMW HA-TA/Gel-TA hydrogels facilitated extracellular matrix production. These findings show the potential of Gel-TA-modified HA-TA hydrogels for cartilage tissue engineering, with the opportunity for further optimization through the incorporation of bioactive components.