Dilution‐Driven Regulation of Biostimulatory Signaling in Calcium Hydroxylapatite– PRGF Systems: Implications for Early Dermal Remodeling

Background Calcium hydroxylapatite (CaHA)‐based fillers act as both volumizing agents and bioactive scaffolds capable of inducing matrix synthesis and dermal remodeling. Their rheological properties and biological activity can be modulated via dilution strategies, expanding their applicability in regenerative and aesthetic medicine. Plasma rich in growth factors (PRGF), a leukocyte‐poor autologous platelet concentrate, represents a biologically active diluent that may modulate the biological response to CaHA. This study evaluated key In vitro biological effects of diluting Radiesse, a biostimulatory soft‐tissue filler composed primarily of synthetic CaHA microspheres suspended in an aqueous carboxymethylcellulose gel carrier, with different PRGF formulations at clinically relevant ratios. Methods Adhesion and proliferation assays, together with gene expression analyses of key extracellular matrix (ECM) remodeling markers, were conducted in human dermal fibroblasts (HDFs) in order to evaluate the biological response of primary human dermal fibroblasts to undiluted and PRGF‐diluted Radiesse formulations at 24 and 72 h. Results The incorporation of PRGF significantly modulated the biological response of HDFs when compared with undiluted CaHA in a dilution‐ and time‐dependent manner. Relative to undiluted CaHA, PRGF‐based conditions enhanced fibroblast adhesion and proliferation. Gene expression analyses revealed a temporally regulated extracellular matrix (ECM) remodeling profile, characterized by a reduction in collagen expression, an increase in FGF2 transcripts at 72 h and an earlier increase in MMP1 mRNA. CTGF transcript levels remained largely unchanged following dilution, suggesting attenuation of sustained profibrotic signaling. However, functional outcomes, including cell adhesion and proliferation, exceeded the magnitude predicted by transcriptional changes. Conclusions PRGF dilution modulates the early biological activity of CaHA‐based fillers by promoting fibroblast adhesion and proliferation while shifting extracellular matrix remodeling toward a dynamic turnover state, supporting its potential as a biologically active strategy to optimize regenerative endpoints. These findings support further investigation of PRGF as a biologically active diluent for CaHA‐based fillers.