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.

Therapeutic compression materials and wound dressings for chronic venous insufficiency: A comprehensive review

“…Figure b,c presents a schematic diagram of drug released dressings with dual delivery systems (i.e., water molecules and drug supply) for ulcer management. The incorporated drugs are commonly enzymes (Singer, Tassiopoulos, & Kirsner, ) and various growth factors (Park, Hwang, & Yoon, ). Normal tissue regenerations are controlled by cellular activities of various growth factors intrinsically involved in human body.…”

Review: Multimodal bioactive material approaches for wound healing

“…13,15,16 Growth factors have a role in cellular migration, proliferation, and adhesion. 17 Target cells include keratinocytes and fibroblasts, which are involved in reepithelialization and collagen deposition, respectively.…”

“…3,18 However, another study was unable to reproduce the accelerated wound healing results of rhPDGF in their diabetic mouse model, despite observing increased granulation tissue, 19 and repeated exposure has been linked to increased cancer malignancy by the FDA. 16 Regranex gel has defined our understanding of growth factor mediated gels for wound healing, and the use of PDGF has been common for many years. [20][21][22][23][24] Other commonly used growth factors include the epidermal growth factor (EGF), [25][26][27][28][29][30][31] fibroblast growth factor (FGF), 21,26,27,32,33 and vascular endothelial growth factor (VEGF).…”

“…Common strategies for delivering growth factors is mixing and encapsulating the growth factor in a biomaterial delivery system 16 (Table I). This is the simplest strategy, and results in a rapid release of the growth factor followed by a slow sustained release.…”

“…30 This field, however, has faced challenges derived from the low stability of growth factors in an in vivo setting, a short half-life, and unwanted side effects as a result of immunogenicity of recombinant proteins. 16,37 As an alternative, growth factor gene delivery has seen an increase in popularity for its long shelf life and stability, in conjunction with low cost for manufacturing. The use of materials containing complementary DNA (cDNA) has led to an extended period of high growth factor concentration with more recognizable proteins in comparison to recombinant proteins.…”