Project R-17043

Native Chemical Ligation for Injectable Microgel Bioconjugation (CLIMB) (Research)

Current tissue engineering solutions for cartilage repair often fail due to poor lateral integration and mechanical instability at the implant-tissue interface. To address these challenges, the CLIMB (Native Chemical Ligation for Injectable Microgel Bioconjugation) project proposes a novel, two-stage bioorthogonal assembly strategy utilizing hyaluronic acid (HA) microgels. The core innovation lies in using Native Chemical Ligation (NCL) as a thiol-regenerative mechanism: C-terminal thioesters on the HA backbone react with N-terminal cysteine peptides to achieve high-density grafting of functional peptides, while simultaneously regenerating free thiols. These regenerated thiols are then utilized for subsequent crosslinking via radical-induced thiol-norbornene click chemistry to form monodisperse microgels. The resulting microgels are decorated with a library of functional peptides, including ECM-affinity sequences for collagen type II and chondroitin sulfate to improve anchoring to host tissue, and transglutaminase-sensitive motifs to enable the formation of microporous annealed particle scaffolds (MAPS). This acellular, injectable platform offers a versatile and minimally invasive alternative to traditional surgical interventions for delaying the onset of osteoarthritis.

01 November 2026 - 31 October 2030