Transepidermal Delivery of Calcium Hydroxyapatite (CaHA) Microneedling: A Novel Approach for Inducing Collagen Types III and IV

Background/Objectives: Microneedling is increasingly applied to enhance transepidermal drug delivery. Calcium hydroxyapatite (CaHA) has recognized biostimulatory properties, but its delivery and distribution within the dermis remain poorly characterized. This study aimed to evaluate the efficacy of microneedling for transepidermal CaHA delivery, focusing on retention, dispersion, and collagen expression, and to investigate the role of hyaluronidase in modulating these effects. Methods: Fluorescently labeled CaHA nanopowder was characterized using scanning electron microscopy (SEM) and confocal fluorescence microscopy. Nine experimental groups were established, varying microneedling intensity and hyaluronidase application. Ex vivo porcine skin samples were analyzed histologically for CaHA penetration and distribution. HaCaT keratinocyte cultures were treated with CaHA, and mRNA expression of collagen types I, III, IV, and MMP-1 was quantified. Results: High-intensity microneedling improved CaHA retention but caused tissue damage. Low-intensity microneedling showed limited retention, enhanced by hyaluronidase co-application. In vitro, CaHA increased collagen type III and IV expression, while collagen type I and MMP-1 remained unchanged. Conclusions: Microneedling effectively delivers CaHA into the dermis and stimulates collagen remodeling. Optimizing microneedling intensity is essential to balance efficacy and safety, and hyaluronidase may enhance clinical outcomes by improving CaHA distribution.