Ultrafast crosslinking, strongly adhesive <i>de novo</i> protein hydrogels promote cartilage regeneration

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Osteoarthritis (OA) is a prevalent degenerative joint disease and the leading cause of chronic pain and disability, affecting millions of people worldwide. In the early stages, shallow cartilage lesions serve as the primary pathological driver, leading to progressive cartilage deterioration and the development of OA. These lesions are characterized by irregular shape and depth, with an inherent anti-adhesive extracellular matrix (ECM), and a poor niche for tissue regeneration, currently lacking effective clinical interventions. Despite extensive efforts, few tissue engineering-based therapies simultaneously address both the demands of robust adhesion to host tissue, support for cell adhesion, and promotion of regeneration for partial-thickness cartilage defects. Here, we report a de novo engineered protein adhesive hydrogel that displays ultrafast gelation, robust tissue adhesion, and maintains chondrocyte phenotype. Tyrosine, lysine, and RGD motifs were precisely encoded into the protein backbone by genetic engineering to enable visible light-triggered covalent bonding, electrostatic interactions with negatively charged cartilage ECM, and enhanced cell adhesion. Molecular weight was tailored by extending monomer repeats to further improve the mechanical performance. Importantly, this genetically engineered protein hydrogel demonstrated ultrafast gelation ( in vitro and in vivo

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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