Limited Added Effect of Proline-Rich P6 Peptide to Cross-Linked Hyaluronic Acid After Partial Lateral Meniscectomy in Sheep.

This study evaluates whether a proline-rich P6 peptide provides added benefit to a cross-linked hyaluronic acid (HA) hydrogel after partial lateral meniscectomy-associated osteoarthritis-like change in sheep. The corrected four-group framework includes Intact no-surgery/no-injection reference knees (n = 7) and 16 surgically injured knees from eight sheep assigned to Mnx (meniscectomy only, n = 4), Mnx + HA (n = 6), or Mnx + HA + P6 (n = 6). Mnx + HA and Mnx + HA + P6 knees received intra-articular injections at Weeks 0, 1, 2, and 4. Osteochondral tissues were evaluated at Week 12 by microCT, H&E scoring, and histochemical/immunohistochemical image analysis. Endpoint-specific animal- or knee-level models were used, with sheep identity included as a random effect when estimable. HA-based treatment was associated with favorable trabecular microCT patterns after meniscectomy. However, the primary Mnx + HA + P6 versus Mnx + HA contrast was not significant for percent trabecular bone volume/BV/TV (+1.52 percentage points; 95% CI -2.22 to 5.26; p = 0.427). Histology and IHC/histochemical findings showed selected exploratory tissue-pattern signals, including collagen-associated matrix staining, but did not establish consistent peptide-specific superiority. These findings support cross-linked HA as an intra-articular biomaterial platform while defining requirements for confirmatory HA-peptide hydrogel studies.