The effect of Stromal cell Derived Factor-1 (SDF-1) and collagen-GAG (Glycosaminoglycan) scaffold on skin wound healing

Abstract

Wound healing is an intricate biological process requiring the appropriate balance of matrix and growth factors. Apart from causing physical deformity, adult wound healing results in the formation of scar tissue, which can hinder functionality and mobility due to excessive wound contraction. Wound care is a significant clinical problem for chronic wounds (eg. diabetic ulcers), acute injuries (eg. burns) and in elective surgeries (eg. scar revision). With an overall annual cost of $16 - 22 billion, wounds severely burden the U.S. healthcare system, and are the fastest growing area in the medical sector. Thus, the goal of promoting faster healing with "scar-less" wound resolution remains unchanged. Skin substitutes, such as IntegraTM and AllodermTM, have been developed to treat chronic wounds and extensive burns. However, they are susceptible to infection, prone to shearing and exhibit poor biodegradation. These limitations could potentially be overcome by expediting blood vessel growth which would promote a more rapid integration of the skin substitute with the surrounding tissue. Experimental evidence also suggests that down-regulating inflammatory cells and up-regulating stem cells and progenitors cells would yield less scar formation. But, these therapies require an expensive isolation and culturing process from the patient's bone marrow. Additional risks include immune rejection concerns, limited shelf-life and stringent storage requirements. To meet this need, a stem cell-attractant and inflammatory cell-repellant chemokine, Stromal cell Derived Factor-1 (SDF-1) was incorporated into a highly porous collagen-glycosamino-glycan (GAG) matrix (skin substitute). The hypothesis is that this enhanced skin substitute would expedite wound healing and decrease abnormal scarring by a mechanism where stem cells from the patient's circulation would be attracted to the wound site while inflammatory cells would be repelled.

(cont.) The purpose of this study is, thus, to elucidate the potential of SDF-1 to improve skin wound healing. Experimental results demonstrated that topical application of SDF-1 induced changes in wound healing kinetics (contraction and re-epithelialization) compared to spontaneous healing in un-treated wounds (Control group). A reproducible dorsal full-thickness excision wound model in wild-type mice was used and wound repair was assessed both macroscopically and microscopically. The SDF-1 treated group demonstrated the fastest rates of wound closure and cell proliferation as compared to the Control group, with re-epithelialization occurring more rapidly by 36%. Qualitatively, the amount of early cell infiltrate in the SDF-1 group was also significantly less when compared to the Control group, which is indicative of a decreased inflammatory response. In addition, wounds treated with SDF-1 exhibited reduced wound contraction initially during the healing process. These experimental results demonstrated a synergy between SDF-1 and the scaffold that promoted faster wound closure and reduced contraction. Thus, the SDF-1 treated-dermal matrix may be a new tool to stimulate wound closure and quality tissue formation in acute and chronic wounds. Other potential applications include tissues that exhibit poor regeneration after injury, such as cornea, spinal cord and heart. The development of such solutions would, therefore, be of significant benefit to human health.