Initial Immunomodulation Using Mg(OH)(2) Promotes Renal Regeneration via Anti-Inflammatory Processes

Abstract

Immunomodulation should be an important consideration when using polylactic acid-polyglycolic acid copolymer (PLGA) based scaffolds, because the initial acute immune response prevents tissue regeneration. To achieve initial immunomodulation, magnesium hydroxide [Mg(OH)(2)], which is known to neutralize the acidity resulting from the PLGA degradation products, was incorporated into the PLGA scaffold. To investigate the in vivo effect Mg(OH)(2), PLGA with Mg(OH)(2) (PLGA/MH) scaffolds were implanted into partial nephrectomy sites in mice, and morphological, histological, molecular-biological and immunohistochemical analyses were performed. The expression of T-cell, pro-inflammatory, and fibrotic factors was lower in the PLGA/MH group than the PLGA group. The PLGA/MH group exhibited a significant increase in host stem cell recruitment. The recruited cells differentiated in situ into renal cells and formed glomeruli. The recruited mesenchymal cells in PLGA/MH group exhibited high levels of anti-inflammatory cytokine expression compared to those in the PLGA group. These results support the concept that targeted tissue regeneration can be stimulated by initial control of the inflammatory and fibrotic microenvironment, and thereby enhancing the processes of host stem/progenitor cell recruitment, in situ differentiation, and anti-inflammatory cytokine secretion.