Enhancing Regenerative Outcomes: Histological Comparison of Hydroxyapatite-Carboxymethylcellulose Combined With Saline vs Platelet-rich Fibrin: A 21-day Study.

BACKGROUND: Calcium hydroxyapatite-carboxymethylcellulose (CaHA-CMC) is a widely used biostimulatory agent that promotes collagen production and tissue remodeling. Platelet-rich fibrin (PRF), rich in growth factors, may enhance this biological response. This study evaluates the subdermal histopathological changes induced by saline solution (SS), PRF, CaHA-CMC + SS, and CaHA-CMC + PRF, with emphasis on early extracellular matrix remodeling and cellular response. METHODS: A prospective study was conducted in 5 patients undergoing subdermal injections of the 4 study groups. Tissue samples were obtained at 21 days postinjection. Hematoxylin and eosin staining was analyzed using a semiquantitative digital histomorphometric surrogate (collagen-associated eosinophilic area). Immunohistochemical analysis for CD45 and collagen (types I, III, and IV) was performed in CaHA-containing groups. Statistical comparisons were conducted using the Wilcoxon signed-rank test. RESULTS: CaHA-CMC + PRF demonstrated a significantly higher collagen-associated eosinophilic area compared to the saline control (3.07 times more; 95% CI: 2.10-4.20; P = 0.04), indicating increased collagen-associated matrix deposition. PRF alone showed a mild, nonsignificant increase, whereas CaHA-CMC + SS remained comparable to control. Immunohistochemistry revealed increased CD45+ cellular clustering and more diffuse collagen deposition in the CaHA-CMC + PRF group compared to CaHA-CMC + SS, supporting enhanced cellular recruitment and extracellular matrix organization. CONCLUSIONS: The addition of PRF to CaHA-CMC appears to potentiate early subdermal tissue remodeling and cellular response. These findings suggest a synergistic biological effect; however, larger studies are required to confirm long-term clinical implications.