Insulin-like growth factor-I and wound healing, a potential answer to non-healing wounds: A systematic review of the literature and future perspectives

Abstract

The induction of wound healing by insulin-like growth factor-I (IGF-I) has been demonstrated in several animal studies; however, there are disproportionately fewer studies assessing its value in humans. The aim of the present review is to provide a comprehensive summary of all the available evidence pertaining to the effects of IGF-I administration on the process of wound anaplasias, both in human tissues in vivo and in cells in vitro. A systematic search of Medline, Scopus and Google Scholar was performed for relevant studies published until May 2020. Overall, 11 studies were included. Of these, 2 studies were conducted in human subjects, whereas the rest of them were performed using in vitro models of human cell lines. All studies demonstrated a positive association between IGF-I and wound anaplasias; IGF-I promoted the migration of keratinocytes, thus playing an important role in wound epithelialization as well as enabling wound bed contraction, and it also stimulated hyaluronan synthesis. The wound healing-promoting effect of IGF-I may be a great asset in dealing with the healing of challenging wounds; thus, this type of treatment could be extremely useful in addressing patients with large burn wounds, chronic diabetic ulcers and patients with impaired wound healing. Nevertheless, the route of recombinant IGF-I administration, the recommended dosage, as well as the indications for clinical use of this growth factor remain to be determined and thus, additional clinical trials are required, with a focus on the medical use of recombinant IGF-I in wound anaplasias.

Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels

“…Potential therapeutic applications of such a hydrogel system are within the area of bioresponsive wound sealants that enable the targeted growth factor release at the incision site due to an excess of MMPs. [98][99][100] Another potential application is the use of the POx-b-POzi hydrogel system for the regeneration of cartilage tissue. Cellular approaches such as the administration of chondrocytes or stem cells remain challenging and often need to be supported by external growth factors.…”

Extracellular Vesicles derived from Apis mellifera Royal Jelly promote wound healing by modulating inflammation and cellular responses

“…Most interesting for wound healing is the secretory profile of MSCs, since tissue-resident MSCs modulate the wound bed by secreting a variety of proteins. Among the most important ones are i) IGF, a chemotactic agent for endothelial cells that stimulates hyaluronan as well as increasing fibroblast and keratinocyte migration (46); ii) FGF, that displays an anti-fibrotic effect by decreasing myofibroblast differentiation and fibronectin (47,48); iii) HGF, that increases migration, proliferation, and matrix metalloproteinase production of keratinocytes as well as increases dedifferentiation of epidermal cells (49)(50)(51), and iv) VEGF, that increases angiogenesis, collagen deposition, and epithelization (52). Overall, RJEVs significantly increased IGF, HGF, and VEGF secretion, but not FGF, indicating a more pro-angiogenic and pro-migratory effect in wound healing, and only minor effects on scarring and fibrosis.…”

Signaling pathways in cutaneous wound healing

“…In the damaged tissue, monocytes are activated, which become macrophages and they mediate phagocytosis as well as the production of growth factors such as platelet-derived growth factor (PDGF), tumor necrosis factor (TNF), and transforming growth factor (TGF-β). Growth factors influencing wound healing include PDGF, which increases macrophage migration and collagen synthesis, promotes granulation tissue formation and accelerates epithelialization, fibroblast growth factor (FGF) supporting angiogenesis and fibroblast proliferation, insulin-like growth factor (IGF-1) increasing fibroblast proliferation, collagen synthesis and epithelialization (Patel et al, 2019;Garoufalia et al, 2021). Decreased IGF-1 expression in diabetic individuals has been reported, which in turn has slowed the healing process (Garoufalia et al, 2021;Liu et al, 2021).…”

“…Growth factors influencing wound healing include PDGF, which increases macrophage migration and collagen synthesis, promotes granulation tissue formation and accelerates epithelialization, fibroblast growth factor (FGF) supporting angiogenesis and fibroblast proliferation, insulin-like growth factor (IGF-1) increasing fibroblast proliferation, collagen synthesis and epithelialization (Patel et al, 2019;Garoufalia et al, 2021). Decreased IGF-1 expression in diabetic individuals has been reported, which in turn has slowed the healing process (Garoufalia et al, 2021;Liu et al, 2021). Many (23 types) of FGF have been identified and divided into seven subfamilies.…”