Preparation and characterization of branched polymers as postoperative anti-adhesion barriers

Abstract

Homopolymers and copolymers synthesized from biocompatible monomers with polyethylene glycol (PEG) and polycaprolactone side chains, were applied to separate healing tissues and prevent postsurgical adhesions. The results of the contact angle and the ESCA spectra reveal the presence of more PEG segments on the surface of the PEMC1 film than the P(EM)₃(EMC4)₁ film. The effects of the molecular structures on the surface properties, including the wetting properties and the anti-tissue adhesion behaviors, of the films were examined. Fluorescent polymer was fixed on the surface of the film to form the marking dot. The in vivo degradation behaviors of the surface-marked films were investigated non-invasively by monitoring the location of the fluorescent signal. The degradation behaviors of various films observed in the animal study were consistent with those observed by in vivo imaging. Proper arrangement of PEG segments on the polymer side chain helped to keep a large proportion of PEG segments close to the surface of the film. Such an arrangement represents an effective means of preventing postoperative tissue adhesion.

Introduction

Postoperative tissue adhesions frequently occur following abdominal operations. They may cause problems such as chronic pelvic pain, bowel obstruction, and infertility [1]. Various methods have been developed to prevent adhesion formation. One common approach is to establish a physical barrier between injured surfaces. Such a barrier can be a film or a gel. Several potential therapeutic products use hyaluronic acid (HA) as a base. However, HA degrades quickly and disappears from the injured site soon after application. Further crosslinking treatment [2], [3] of HA is required to improve the efficacy of the barrier in preventing adhesion. Synthetic polymers are sometimes preferred over natural materials as physical barriers because the former are easier to handle, contain fewer biological contaminants, and exhibit less immunogenicity. Polymeric films [4], [5], [6] have been applied as barrier films to reduce postsurgical adhesion. Polycaprolactone–poly(ethylene glycol) block copolymer (PCL-b-PEG) is a biodegradable polymer. The degradation rate of the PCL-b-PEG increased with increasing PEG content [7]. Nanoparticles of amphiphilic PCL-b-PEG block copolymer have been employed for drug release applications [8]. However, no application of the PCL–PEG copolymer as an adhesion preventative barrier has yet been found. Huang et al. [9] examined the degradation characteristics of poly(ɛ-caprolactone)-based copolymers and blends. They found that the degradation rate of PEG–PCL copolymer is lower than those of poly(ethylene glycol)–polycaprolactone–polylactide (PEG–PCL–PLA) copolymer. Therefore, the anti-adhesion property of PEG–PCL copolymer is worthy of study. Complex biological phenomena are visualized by the bioimaging process. Its applications have been extended to therapy and high-throughput drug screening [10]. In vivo drug distribution profiles were determined by fluorescence imaging [11].

In this work, the homopolymer and copolymer that contained biocompatible monomers with polyethylene glycol–polycaprolactone side chains were employed to establish a physical barrier between surgically damaged surfaces. Polyethylene glycol and polycaprolactone are hydrophilic and hydrophobic segments, respectively. The distribution of polyethylene glycol and polycaprolactone close to the surface of the film changed the surface properties of the film. The anti-adhesion performance of the barrier film was evaluated by a non-invasive method [12] and the direct observation in the animal study. The goal of this study is to evaluate the effects of the polymer chemical structure (homopolymer or copolymer) on the surface properties and tissue anti-adhesion properties.