Neo-Dermis Formation and Graft Timing After ADM Reconstruction: A Cohort Study with Histological Validation

Abstract

Acellular dermal matrices (ADMs) are widely used in soft-tissue reconstruction, yet the optimal timing for split-thickness skin grafting (STSG) remains unsettled. We conducted a single-center retrospective cohort study (January 2023–August 2025) of adults undergoing ADM-based reconstruction with Integra® Double Layer (IDL), Integra® Single Layer (ISL), or Nevelia®. Primary endpoints included length of stay (LOS), STSG requirement and timing, and in-hospital complications; secondary endpoints included spontaneous epithelialization. Prespecified adjusted analyses (linear/logistic models) controlled for age, sex, etiology, anatomical site, diabetes/PAOD, smoking, wound size (when available), wound contamination, and matrix type. Histology and immunohistochemistry (H&E, Masson trichrome, CD105, D2-40) assessed matrix integration and vascular/lymphatic maturation. Seventy-five patients were included (IDL n = 40; ISL n = 20; Nevelia n = 15). On multivariable analysis, matrix type was not an independent predictor of LOS (ISL vs. IDL β = +2.84 days, 95% CI −17.34 to +23.02; Nevelia vs. IDL β = −4.49 days, 95% CI −16.24 to +7.26). Complications were infrequent (6/75, 8.0%) and comparable across matrices; spontaneous epithelialization occurred in 3/75 patients (4.0%). A day-14 grafting strategy, applied only after documented clinical integration, was feasible in 30/75 (40.0%) patients without excess complications. Histology/IHC at 3–4 weeks demonstrated CD105-positive, perfused capillary networks with abundant collagen; at 4–6 weeks, D2-40-positive lymphatic structures confirmed progressive neo-dermis maturation, supporting the biological plausibility of earlier grafting once integration criteria are met. In this cohort, outcomes were broadly similar across matrices after adjustment. A criteria-based early STSG approach (~day 14) appears safe and operationally advantageous when integration is confirmed, while a minority of defects may heal without grafting. Prospective multicenter studies with standardized scar/functional measures and cost analyses are needed to refine patient selection and graft timing strategies.