Abstract
Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40–60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries.
Highlights
Wounds that penetrate deep in the skin remain a major clinical problem because of morbidity associated with prolonged periods required for repair and regeneration of the injured tissue, bleeding, risk for infections and septicemias, keloids, and scar formation
This review describes the natural anti-Gal Ab, α-gal nanoparticles, and experimental models in which anti-Gal/α-gal nanoparticles interaction accelerates wound healing
Demonstration of meniscus like fibrocartilage generation in such sponge discs suggested that stem cells recruited into these PVA sponge discs by secretions from activated macrophages were “instructed” by the meniscus cartilage extracellular matrix (ECM) fragments to differentiate into fibrochondroblasts that produce fibrocartilage [67]
Summary
Wounds that penetrate deep in the skin remain a major clinical problem because of morbidity associated with prolonged periods required for repair and regeneration of the injured tissue, bleeding, risk for infections and septicemias, keloids, and scar formation. Based on the extensive in vitro interaction between antiGal and α-gal nanoparticles, it could be expected that, following topical application of these nanoparticles to wounds, they will readily bind the natural anti-Gal Ab that is released from ruptured blood vessels within the wound and is present in the fluid film in wounds As schematically illustrated, this Ag/Ab interaction activates the complement system, generating chemotactic peptides that recruit macrophages which bind the anti-Gal coated nanoparticles and produce cytokines and growth factors that orchestrate the healing of wounds [19,20,21, 23]. In vivo studies on anti-Gal mediated effects of α-gal nanoparticles cannot be performed in standard experimental animal models since mice, rats, guinea-pigs, rabbits, and pigs (as well as other nonprimate mammals) all produce αgal epitopes on their cells by the glycosylation enzyme α1,3galactosyltransferase (α1,3GT) [37, 38]. Both GT-KO mice and GTKO pigs were found to be suitable experimental models for studying the effects of α-gal nanoparticles on wound healing [19,20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
