Development of an Injectable Biphasic Hyaluronic Acid‐Based Hydrogel With Stress Relaxation Properties for Cartilage Regeneration

• Published in: Advanced healthcare materials Vol. 13; no. 18; pp. e2400043 - n/a
• Main Authors: Kim, Han‐Sem, Li, Cheng Ji, Park, Sung‐Min, Kim, Kyung Wook, Mo, Ji‐Hun, Jin, Guang‐Zhen, Lee, Hae‐Hyoung, Kim, Hae‐Won, Shin, Ueon Sang, Lee, Jung‐Hwan
• Format: Journal Article
• Language: English
• Published: Germany 01.07.2024
• Subjects: adjustable remodeling property; Animals; biphasic chondrogenesis; Cartilage - drug effects; Cartilage - physiology; Chondrogenesis - drug effects; Humans; Hyaluronic Acid - chemistry; Hyaluronic Acid - pharmacology; Hydrogels - chemistry; Hydrogels - pharmacology; injectable hydrogel; Mice; Regeneration - drug effects; Stress, Mechanical; stress‐relaxing hydrogels; Tissue Engineering - methods; tissue regeneration; injectable hydrogel; tissue regeneration; stress‐relaxing hydrogels; adjustable remodeling property; biphasic chondrogenesis
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202400043

Biomimetic stress‐relaxing hydrogels with reversible crosslinks attract significant attention for stem cell tissue regeneration compared with elastic hydrogels. However, stress‐relaxing hyaluronic acid (HA)‐based hydrogels fabricated using conventional technologies lack stability, biocompatibility, and mechanical tunability. Here, it is aimed to address these challenges by incorporating calcium or phosphate components into the HA backbone, which allows reversible crosslinking of HA with alginate to form interpenetrating networks, offering stability and mechanical tunability for mimicking cartilage. Diverse stress‐relaxing hydrogels (τ1/2; SR50, 60–2000 s) are successfully prepared at ≈3 kPa stiffness with self‐healing and shear‐thinning abilities, favoring hydrogel injection. In vitro cell experiments with RNA sequencing analysis demonstrate that hydrogels tune chondrogenesis in a biphasic manner (hyaline or calcified) depending on the stress‐relaxation properties and phosphate components. In vivo studies confirm the potential for biphasic chondrogenesis. These results indicate that the proposed stress‐relaxing HA‐based hydrogel with biphasic chondrogenesis (hyaline or calcified) is a promising material for cartilage regeneration. Injectable biphasic hyaluronic acid‐based hydrogels offer a customized platform for tissue regeneration by controlling their remodeling properties. In vitro and in vivo experiments demonstrate the potential for biphasic cartilage regeneration facilitated by stress relaxation ability and functionalization effects, indicating their potential for stem cell therapy and as a platform for customized tissue regeneration.