Direct Contact with CaHA Microspheres Drives ECM Stimulation In Vitro

Calcium hydroxyapatite (CaHA)-based dermal fillers have been shown to help counteract and potentially reverse certain aspects of skin aging. By applying isolated CaHA microspheres, we investigated the importance of the direct contact of dermal cells to microspheres and their role for the expression of extracellular matrix (ECM) components. To this end, human dermal fibroblasts were cultured in the presence of CaHA microspheres. Cell migration, cell–microsphere interaction, and CaHA dose-dependent effects on the expression of ECM proteins were examined using microscopy, mRNA and protein expression analysis. Our results indicated that fibroblasts established direct and close contact to CaHA microspheres. This interaction was associated with a time- and dose-dependent increase in ECM protein expression, including collagen-1, emilin-1, elastin, fibulin-5, fibronectin, and the proteoglycans—lumican and versican. These observations indicate that direct contact between fibroblasts and CaHA microspheres promotes ECM protein expression, suggesting a role for this interaction in supporting skin regeneration and counteracting age-related changes, potentially augmented in vivo by immunomodulatory effects.