Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration

Abstract

Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.

Keywords: chronic wound; drug delivery system; growth factor; wound healing.

Figure 1

Cutaneous wounds 3 (A) and 5 days (B) after injury. Growth factors such as fibroblast growth factor (FGF), insulin-like growth factor (IGF), keratinocyte growth factor (KGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), and vascular endothelial growth factor (VEGF), and proteases such as matrix metalloproteinases (MMPs) and plasminogen activator (PA) are thought to be necessary for cell movement [reproduced with permission from Singer, A.J.; Clark, R.A. Cutaneous wound healing. N. Engl. J. Med. 1999, 341, 738‒746].

Figure 2

Schematic illustration of growth factor-loaded drug delivery systems (DDSs) for enhanced wound healing. DDSs were classified according to their matrix structures, i.e., particulate systems, scaffolds, hydrogels, and miscellaneous strategies.