The potential of topical and injectable growth factors and cytokines for skin rejuvenation.

Growth factors and cytokines (referred to collectively hereafter as GFs) control cell growth, proliferation, and differentiation via a network of inter and intracellular signaling pathways. There are striking parallels between the pathways involved in skin wound healing and those implicated in photoaging of the skin. In recent years, topical and injectable GFs have emerged as an intriguing therapeutic modality that can be harnessed for aesthetic and medical purposes. This article provides a review of available evidence for the role in skin regeneration of topical GFs, and of injectable GFs contained in autologous platelet-rich plasma (PRP). It presents data from recent studies of GFs, offers a discussion of their potential to serve as antiaging actives, and includes safety considerations. As studies of injectable GFs typically assume preexisting familiarity with PRP protocols and the theory behind them, explanatory notes are provided. An assessment is provided of the evidence gaps that exist currently between experimental observations regarding GFs and their proven clinical benefits. Data of evidence levels II and III support the use for skin rejuvenation of topical GFs derived from sources including secretions or lysate of human dermal fibroblasts, and secretions of the snail Cryptomphalus aspersa. GFs with associated stem cell proteins, secreted by human dermal fibroblasts under hypoxic stress, can accelerate skin healing after laser resurfacing. In vitro and animal studies, small case series of PRP-treated patients and one prospective clinical study of its variant, platelet-rich fibrin matrix (PRFM), suggest the value of injectable GFs for skin rejuvenation. However, data of higher power are required to expand this proof of concept into an evidence-based paradigm. The clinical applications of topical and injectable GFs are promising, and remain to be fully defined. With continued study, data of higher evidence level can be accrued and formulations can be developed that offer optimal clinical efficacy, safety, tolerability, and stability. Better understanding of the mechanism of action of GFs can potentially advance our general understanding of dermal signaling pathways, and hence of hyaluronic acid and other alloplastic fillers; and allow the development of protocols for synergistic combination of GFs with other skin rejuvenation modalities.