Regeneration of an Extracellular Matrix Ecosystem Following Subcutaneous Injection With Different Radiesse Dilutions: A Histologic and Ultrasound Study

ABSTRACT Background Calcium hydroxylapatite‐carboxymethylcellulose (CaHA‐CMC) stimulates neocollagenesis across a range of dilutions; however, the magnitude and temporal profile of this bioregenerative response have not yet been comprehensively examined. Objective To assess collagen, elastin, and proteoglycan expression, as well as elastosis, microcirculation, and skin thickness after injection of undiluted and diluted CaHA‐CMC. Methods In this prospective, single‐site study (NCT06093815), 10 adults undergoing abdominoplasty were injected subcutaneously into the pannus with CaHA‐CMC (+), CaHA‐CMC 1:1, CaHA‐CMC 1:2, and saline control 6 months, 3 months, and 14 days before surgery. Skin thickness, elastosis, and microcirculation were measured with ultrasound, and collagen, elastin, decorin, versican, and fibulin‐5 were quantified using histology and immunohistochemistry. Continuous outcomes were analyzed using mixed‐effects models, and paired categorical outcomes were analyzed using the Stuart–Maxwell test and repeated‐measures proportional‐odds ordinal models. Results Elastosis improved at 6 months for CaHA‐CMC (+) and CaHA‐CMC 1:1, and skin thickness increased significantly at 3 months for CaHA‐CMC (+) and at 3 and 6 months for CaHA‐CMC 1:1. Microcirculation also improved over time for all CaHA‐CMC dilutions, with the strongest and most consistent changes observed for CaHA‐CMC 1:1. Collagen deposition was significantly greater than saline at all time points for all dilutions, with the highest levels observed at 3 months for CaHA‐CMC 1:1. Decorin and versican were elevated at 3 months, whereas fibulin‐5 increased at 6 months, particularly for CaHA‐CMC 1:2. Conclusion CaHA‐CMC induces coordinated ECM remodeling, with the most consistent overall improvements observed for CaHA‐CMC 1:1, supporting its use for bioregenerative skin quality improvement.