The Use of Senolytic Agent to Improve the Benefit of Platelet-Rich Plasma and Losartan for Treatment of Femoroacetabular Impingement and Labral Tear: A Pilot Study
Abstract
Abstract: Femoroacetabular impingement (FAI) and labral tears can cause hip pain, which decreases function and can lead to osteoarth ritis (OA). Arthroscopic treatment of FAI eliminates pain and delays progression of OA by preventing further cartilage damage. Plate let-Rich Plasma (PRP), an orthobiologic treatment containing a mixture of growth factors beneficial for tissue repair, has been used to improve outcomes after surgical treatment of FAI and labral tears. It is known that TGF-1, a cytokine found in high levels in P RP, induces fibrosis which can impede cartilage regeneration and cause aberrant scar tissue formation within the hip. We have shown administration of the TGF- 1 blocker, losartan, improves the benefit of PRP in hip arthroscopy and, currently a combination of PRP and losartan, have become a standard of care for FAI and labral tears at the Steadman Clinic. However, senescent cells, which releas e pro-inflammatory cytokines/chemokines, proteases, and other senescence-associated secretory phenotypes (SASP) are present in PRP, especially in older patients. We believe these cells decrease the benefit of PRP/losartan and that administration of a senolytic age nt to eliminate senescent cells and reduce SASPs may improve the benefit of PRP/losartan. Thus, we posit that pre- and post-operativ e administration of Fisetin, a senolytic agent, will enhance the beneficial effect of PRP/losartan. We propose to perform a randomiz ed, double-blind, placebo-controlled clinical trial in which patients undergoing arthroscopic treatment of FAI and labral tear and t reated with standard of care (PRP and losartan) will be given Fisetin or placebo both pre- and post-operatively. Serum biomarkers re lated to cartilage degeneration, inflammation, cellular senescence, fibrosis and, pain will be assessed at baseline, immediately pre -op, 1 week post-op and 8-12 weeks post-op. Patient-reported outcomes for pain and function will be collected at baseline, at 8-12 w eeks post-op and at6, and 12 months post-op. A physical exam will be conducted at baseline and at 8-12 weeks post-op. Improving arth roscopic treatment of FAI will provide long term benefits to civilians and military service members by accelerating healing and redu cing incidence of OA.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 07, 2021
- Source ID
- N000142112716
Entities
People
- Johnny Huard
Organizations
- Office of Naval Research
- Steadman Philippon Research Institute
- United States Navy