Macrophages Recruitment and Activation by !-gal Nanoparticles Accelerate Regeneration and Can Improve Biomaterials Efficacy in Tissue Engineering

This review describes a novel method for accelerating tissue regeneration by !-gal nanoparticles and proposes methods for !-gal nanoparticles mediated increased efficacy of biomaterials used in tissue engineering. !-Gal nanoparticles present multiple !-gal epitopes (Gal!1-3Gal"1-4GlcNAc-R) that bind the most abundant natural antibody in all humansthe anti-Gal antibody, constituting ~1% of immunoglobulins. Anti-Gal/!-gal nanoparticles interaction generates chemotactic complement cleavage peptides that induce rapid and extensive recruitment of macrophages. The subsequent interaction between the Fc portion of anti-Gal coating !-gal nanoparticles and Fc# receptors on macrophages activates these cells to produce cytokines/growth factors that promote tissue regeneration and recruit stem cells. Intradermal injection of !-gal nanoparticles induces localized extensive recruitment and activation of macrophages. These macrophages disappear within 3 weeks without altering normal skin architecture. Application of !-gal nanoparticles onto wounds of anti-Gal producing animals reduces healing time by 40-70%. !-Gal nanoparticles injected into ischemic myocardium induce extensive recruitment of macrophages that secrete cytokines preserving the structure of the ischemic tissue. These macrophages may recruit progenitor cells and/or stem cells that are guided by myocardial microenvironment and extracellular matrix to differentiate into cardiomyocytes. !-Gal nanoparticles applied to nerve injures will recruit macrophages that can promote angiogenesis required for induction of axonal sprouting and thus may regenerate the severed nerve. In tissue engineering, incorporation of !-gal nanoparticles into decellularized tissue and organ implants may improve in vivo regeneration and restore biological function of implants because of accelerated recruitment of macrophages and stem