Characterization of Tissue Histology for Collagenase Clostridium Histolyticum-aaes: Results in Humans Following Abdominoplasty-An Exploratory Pilot Study.

Abstract

Collagenase clostridium histolyticum-aaes (CCH-aaes) is FDA-approved for cellulite treatment but was withdrawn because of high bruising incidence. Histological effects of CCH-aaes in humans remain poorly characterized. The aim of the study was to evaluate histopathologic changes in human subcutaneous tissue following CCH-aaes injection and compare injection techniques to identify strategies that reduce bruising. In this single-center, Phase 2b, nonrandomized, open-label exploratory study, 8 women undergoing elective abdominoplasty received CCH-aaes injections using either a 3-aliquot or a 7-injection hexagonal grid technique. Dosing schedules varied across groups. Excised abdominal tissue was analyzed histologically and immunohistochemically. Pathologists were blinded to injection technique and timing. CCH-aaes induced targeted enzymatic subcision and remodeling of subcutaneous tissue, with collagen degradation, neocollagenesis, and fat-lobule reorganization. The 3-aliquot technique produced more localized, intense histologic changes and greater bruising, whereas the grid technique caused diffuse but milder tissue effects. Bruising correlated with subcutaneous vascular disruption rather than dermal injury. No serious adverse events occurred. AUX-I (clostridial collagenase I-1 of the 2 purified bacterial collagenases in CCH-aaes)-neutralizing antibodies developed in 5 of 8 subjects, with no impact on safety or efficacy. CCH-aaes induces localized subcutaneous remodeling without dermal disruption. The 3-aliquot technique elicits more robust histologic effects but increases bruising risk, whereas the grid method offers a more diffuse, potentially safer alternative. These findings clarify the tissue-level mechanism of CCH-aaes and may guide safer clinical use should the product return to market. For image description, please refer to the figure legend and surrounding text.