INTRODUCTION
Like many pathologies, skin aging is complex. The well-balanced, youthful architecture of young skin relies on the structure of dermis, via a "bed base" supporting youthful skin while fibroblasts are the "craftsmen", producing collagen, hyaluronic acid (HA), and regulating molecules that control skin pigmentation.1,2 Dermal fibroblasts interact with extracellular matrix (ECM) fibers to produce healthy, elastic, hydrated, and unblemished skin.3 Age-related alterations of the structural and mechanical support of the skin's ECM are the driving pathomechanisms of aging skin. Therefore, fibroblasts play a vital role in the skin aging process, and if untreated during intrinsic or extrinsic aging, can contribute to loose, saggy skin with uneven tone. Previous studies have shown that fibroblasts are reduced in numbers and their proliferative and metabolic functions slow with aging.1,4,5 Simultaneously, matrix metalloproteinase concentrations increase with aging and enzymatically contribute to the degradation of the ECM and phenotypic changes associated with aging skin.6,7 Recent findings suggest that senile fibroblasts can be revived and their functions restored, particularly by restoring mechanical tension and cell-substrate contact.8-10 Targeting fibroblast activity, restoring ECM structure and mechanical tension, or mitigating degradative enzyme activity may be ideal targets for anti-aging therapy.11
In recent years, cosmetic dermatology has borrowed many ideas from regenerative medicine, which is loosely defined as the restoration of damaged or diseased tissues and their functions via biochemical or biomechanical cues, and has resulted in the emergence of regenerative aesthetics.12 Several bioregenerative treatments, including calcium hydroxylapatite (CaHA; Radiesse®/Radiesse® (+) (which includes integral lidocaine), Merz Aesthetics), polylactic acid (PLLA; Sculptra®, Galderma), polymethyl methacrylate (PMMA; Bellafill®, Suneva Medical) have been implemented in clinics and have demonstrated the ability to induce synthesis of some endogenous ECM components for contouring tissue in aesthetic indications.10,13,14 Specifically and uniquely among these fillers, CaHA has demonstrated the ability to restore fibroblast function in aged or damaged skin, synthesize type I and type III collagens, elastin, and proteoglycans, and is a promising regenerative aesthetic treatment.14-16
Since its introduction in the aesthetic market in 2006, CaHA has been an efficacious and safe injectable treatment for improving global panfacial volume loss and skin rejuvenation.17 CaHA injectable filler consists of 25-45 um synthetic, immunologically inert, and mechanically-stimulating microspheres suspended in an aqueous gel preparation containing carboxymethyl cellulose
In recent years, cosmetic dermatology has borrowed many ideas from regenerative medicine, which is loosely defined as the restoration of damaged or diseased tissues and their functions via biochemical or biomechanical cues, and has resulted in the emergence of regenerative aesthetics.12 Several bioregenerative treatments, including calcium hydroxylapatite (CaHA; Radiesse®/Radiesse® (+) (which includes integral lidocaine), Merz Aesthetics), polylactic acid (PLLA; Sculptra®, Galderma), polymethyl methacrylate (PMMA; Bellafill®, Suneva Medical) have been implemented in clinics and have demonstrated the ability to induce synthesis of some endogenous ECM components for contouring tissue in aesthetic indications.10,13,14 Specifically and uniquely among these fillers, CaHA has demonstrated the ability to restore fibroblast function in aged or damaged skin, synthesize type I and type III collagens, elastin, and proteoglycans, and is a promising regenerative aesthetic treatment.14-16
Since its introduction in the aesthetic market in 2006, CaHA has been an efficacious and safe injectable treatment for improving global panfacial volume loss and skin rejuvenation.17 CaHA injectable filler consists of 25-45 um synthetic, immunologically inert, and mechanically-stimulating microspheres suspended in an aqueous gel preparation containing carboxymethyl cellulose