Development of poly(D,L-lactic-co-glycolic acid) films coated with biomembrane-mimicking polymers for anti-adhesion activity

Abstract

A physical barrier is one of the most effective strategies to alleviate excessive postoperative adhesion (POA) between tissues at an injury site. To overcome the limitations of current polymeric film-type physical barriers, we suggest a film of poly(lactic-co-glycolic acid) (PLGA) that is non-covalently coated with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (PMB). While maintaining the degradability and mechanical properties of PLGA, the PMB coating introduces strong anti-adhesive properties to the film by forming a zwitterionic MPC-based surface through the hydrophobic interactions between BMA moieties and PLGA. Compared to SurgiWrap®, the commercially available poly(lactic acid)-based anti-adhesive film against POA, the PMB-coated PLGA film is much more inhibitory against protein adsorption and fibroblast adhesion, processes that are crucial to the POA process. PMB coating also inhibits the expression of fibronectin containing extra domain A (FN-EDA), α-smooth muscle actin (α-SMA), and collagen type IV alpha 2 (COL4A2), which are marker genes and proteins involved in fibroblast activation and excessive fibrosis during POA. Such inhibitory activities are clearly observed in a 3-dimensional culture of fibroblasts within a collagen matrix, which mimics the in vivo environment of an injury site, as well as in a 2-dimensional culture. The kinetics and the stability of the PMB coating suggest potential future clinical use to coat PLGA films to create a film-type anti-adhesion barrier that overcomes the limitations of current products.

Keywords: Adhesion barrier; Fibrosis inhibition; PLGA; Poly(MPC-co-BMA) (PMB); Postoperative adhesion (POA).