Injection of cross-linked hyaluronic acid dermal filler into sun-exposed forearm skin of early middle-aged persons stimulates collagen expression in dermal fibroblast

Summary: Abstract Body: Mechanical support and function of the dermis depend on the integrity of the extracellular matrix (ECM), which is primarily composed of type I collagen fibrils in association with other structural proteins, including several types of collagens, proteoglycans, and glycoproteins. Dermal fibroblasts reside within the ECM and coordinately regulate its production, turnover, and maintenance. With the passage of time and chronic exposure to the environment, including ultraviolet irradiation, the dermal ECM becomes fragmented. This loss of structural integrity disrupts interactions between fibroblasts and the ECM. It has been demonstrated that injection of cross-linked hyaluronic acid dermal filler (CL-HA) into sun-protected or sun-exposed skin of elderly individuals (>70 years of age) activates fibroblasts, leading to deposition of new ECM, thereby improving dermal structural integrity. The aim of this study is to investigate the impact of CL-HA injection on dermal fibroblast collagen expression in sun-exposed forearm skin of early middle-aged persons (30-50 years, N=16). Each study participant received injections of CL-HA and its vehicle (saline) in adjacent sites of forearm skin. Skin samples (4 mm punch biopsies) were obtained at one- and three-months post-injection and analyzed using histochemistry, immunohistochemistry, in situ mRNA hybridization, and multiphoton confocal laser scanning second harmonic generation microscopy. Substantial activation of dermal fibroblasts surrounding pockets of injected CL-HA was observed at one-month post-injection and continued for at least three-months. In particular, the expression of type I collagen mRNA and protein significantly increased 44% and 92%, respectively, compared with vehicle injection. Thus, our results show that injection of CL-HA activates dermal fibroblasts and enhances dermal ECM integrity in sun-exposed skin of early middle-aged individuals, similar to that observed in persons of advanced age. Alexandre Ermilov¹, Mio Nakamura¹, Megan Hauptman¹, Reinie Thomas¹, Jeffrey Orringer¹, Frank Wang¹, Gary J. Fisher¹ 1. Department of Dermatology, University of Michigan, Ann Arbor, MI, United States. Translational Studies: Cell and Molecular Biology