Safety and Efficacy of Micronized Acellular Dermal Matrix Injection for Correction of Moderate to Severe Nasolabial Folds: A Double-Blind, Multicenter, Randomized Controlled, Non-inferior Clinical Trial

BACKGROUND: Nasolabial folds (NLFs) are prominent facial lines that deepen with age and may adversely affect facial aesthetics and psychosocial confidence. Injectable fillers, including micronized acellular dermal matrix (mADM), offer minimally invasive correction; however, clinical evidence for mADM's safety and efficacy remains limited. We conducted a double-blind, multicenter, randomized controlled trial to compare an mADM filler (Regenfil) with a regulatory agency-approved cross-linked collagen filler (Sunmax Collagen Implant I-Plus). METHODS: Adults aged ≥18 years with Wrinkle Severity Rating Scale (WSRS) grade 3 or 4 NLFs were randomized to receive mADM or collagen. Six weeks after the initial treatment, a protocol-defined supplemental injection was permitted if additional correction was needed. Outcomes were assessed 6 weeks, 3 months, and 6 months after the last treatment. Efficacy endpoints included blinded-evaluator WSRS, Global Aesthetic Improvement Scale (GAIS) rated by injectors and participants, and participant satisfaction. The prespecified primary endpoint was the percentage of participants achieving a >1-grade WSRS improvement simultaneously on both left and right NLFs. Safety was evaluated by monitoring device-related adverse events and local injection-site reactions. RESULTS: Of 202 randomized participants, 175 completed all required follow-ups for safety and efficacy (mADM, n=86; collagen, n=89). The mADM group required lower mean filling volumes and fewer supplemental injections than the collagen group (P<0.05). At 3 months after the last treatment, the proportion meeting the primary endpoint was 88.4% with mADM versus 85.4% with collagen (P>0.05). At 6 months, efficacy was 70.9% with mADM and 69.7% with collagen (P>0.05). Apart from GAIS and participant satisfaction at 6 weeks, which favored collagen, no statistically significant differences were observed between groups across other efficacy endpoints and timepoints. The most common adverse events were hardening, redness, and skin discoloration at injection sites, occurring at similar frequencies in both groups (P>0.05). Early local reactions such as swelling and pain were more frequent with mADM (P<0.05), but were predominantly mild to moderate and resolved within one week. No treatment-related serious adverse events were reported. CONCLUSION: In this multicenter, randomized, double-blind trial, mADM demonstrated safety and effectiveness for correcting moderate-to-severe NLFs, with outcomes comparable to a cross-linked collagen filler through 6 months. Compared with collagen, mADM achieved similar correction with less product volume and fewer supplemental injections, while showing a transient increase in early local reactions that were self-limited. These findings support mADM as a minimally invasive, injectable tissue-regenerative bioscaffold and a viable alternative for facial rejuvenation. BULLET POINT LIST: Comparable Efficacy: mADM filler demonstrated similar effectiveness to collagen fillers in reducing moderate-to-severe nasolabial folds. Enhanced tissue remodeling: Histological analysis showed that mADM promotes collagen deposition, fibroblast proliferation, and vascularization. Minimally Invasive & Safe: While early adverse reactions (swelling, pain) were slightly higher with mADM, they were mild, self-limiting, and resolved within a week. Lower Injection Volume Needed: mADM required significantly less filler volume and fewer supplemental injections compared to collagen fillers. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .