Optimal Molecular Weight of Poly(lactic-co-glycolic acid) and Mg(OH)(2) Concentration to Fabricate Anti-Inflammatory Scaffold for Renal Tissue Regeneration

Abstract

Poly(lactic-co-glycolic acid) (PLGA) is a material widely used for medical purposes, but it can cause inflammation via acidic byproducts during degradation in vivo. In vivo PLGA retention can be controlled by molecular weight, and the acidic byproducts can be removed using a neutralizing agent, such as Mg(OH)(2). In this study, three types of scaffold [PLGA 40 kDa/Mg(OH)(2) 5%, PLGA 40 kDa/Mg( OH)(2) 15%, and PLGA 180 kDa/Mg(OH)(2) 15%] were fabricated and in vivo initial inflammation and renal regeneration were evaluated by histological, immunohistochemical, and real-time PCR analyses. The PLGA 40 kDa/Mg(OH)(2) 15% scaffold showed reduced immune cell (CD8(+)) infiltration, inhibited proinflammatory reactions (TNF-alpha, IL-1 beta, IL-6, M-CSF, MCP-1, RANTES, IL-18, OPN, and Col3) and fibrosis (alpha-SMA, Col1, FSP-1, and vimentin), increased expression of anti-inflammatory factors (TGF-beta 1, IL-10, IL-4, IL-2, adiponectin, and adipsin), and enhanced expression of renal tissue differentiation genes (Pax2, Wt1, Emx2, vWF, laminin, Krt10, and cadherin) compared to other scaffolds. Additionally, the PLGA 40 kDa/Mg(OH)(2) 15% scaffold yielded no abnormal morphological or histological characteristics during 40 weeks of observation. The scaffold prepared with 40-kDa PLGA and 15% of Mg(OH)(2) was effective at inhibiting inflammation and stimulating renal regeneration.