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NIH grant 1R01DE036268-01: Breaking the balance of protease activity and ECM remodeling in ligament regeneration
Institute: {'code': 'DE', 'abbreviation': 'NIDCR', 'name': 'National Institute of Dental and Craniofacial Research', 'admin_org_id': '12500070', 'admin_funding_url': ''}. PI: Joanna Marjorie Smeeton. Award: $621950.
Start: 2026-08-06T00:00:00.
PROJECT SUMMARY
There is an urgent need to identify mechanisms that enable scar-free repair of ligaments to restore native
structure and function to improve the treatment of both acute injury and resultant chronic joint diseases. Although
regenerative healing is not seen in mammals, zebrafish are capable of fully repairing complex musculoskeletal
structures without fibrosis. We find that zebrafish tightly regulate ECM turnover following acute ligament injury,
producing a regenerative ECM that integrates seamlessly into functional tissue. In this proposal, we will dissect
the mechanisms that allow zebrafish to remodel their extracellular matrix (ECM) during ligament healing and
uncover molecular insights with direct relevance to human ligament and connective tissue repair. This project is
significant because it addresses a major clinical problem, fibrotic scar formation in ligament injuries, using a
powerful reductionist regenerative model. Ultimately, these studies will reveal novel strategies to promote scar-
free musculoskeletal healing and improve outcomes for human patients with ligament injuries.document fetched 2026-08-16 06:34