Chapter 12 - Acceleration of Wound and Burn Healing by Anti-Gal/α-Gal Nanoparticles Interaction

Abstract

Healing of wounds and burns may be accelerated by applying α-gal liposomes or α-gal nanoparticles to the injured tissue. These liposomes and nanoparticles are made of phospholipids, glycolipids, and cholesterol extracted from rabbit RBC membranes and present multiple α-gal epitopes (~1015 α-gal epitopes/mg). α-Gal nanoparticles are α-gal liposomes that were fractured into much smaller liposomes (<300 nm) by extensive probe sonication. The α-gal nanoparticles also may be prepared of synthetic glycolipids and phospholipids. Both α-gal liposomes and α-gal nanoparticles bind the natural anti-Gal antibody and activate the complement system, resulting in localized production of complement cleavage chemotactic peptides, which induce rapid migration of macrophages into the injury. Anti-Gal bound to α-gal nanoparticles or liposomes further binds to macrophages via Fc/FcγR interaction. This interaction activates macrophages to secrete various pro-healing cytokines and growth factors. Topical application of α-gal nanoparticles or liposomes onto injuries in anti-Gal producing GT-KO mice or pigs accelerates healing of wounds and burns so that the regeneration time of the epidermis is shortened by 40%–60%. This acceleration of wound healing in mice occurs prior to the onset of fibrosis. Therefore, wounds do not develop scars in anti-Gal producing mice treated with α-gal liposomes and nanoparticles. Preliminary studies in mice with chemically induced diabetes impaired wound healing suggest that α-gal nanoparticles can induce healing of wounds, which are chronic and fail to heal without treatment. These nanoparticles and liposomes are highly stable for years in suspension or in a dried state on wound dressings. Studies in GT-KO mice and pigs demonstrated no toxic effects of α-gal nanoparticles on the treated animals. Thus, it would be of interest study the feasibility and efficacy of α-gal nanoparticles in inducing accelerated healing of burns and acute or chronic wounds in humans.