Mucin-inspired bottlebrush polymer hydrogel for postoperative adhesion prevention.

Abstract

Postoperative adhesions pose a significant clinical challenge, contributing to chronic pain, organ dysfunction, increased morbidity, mortality, and substantial healthcare costs. Current adhesion prevention strategies often rely on physical barriers such as solid films, polymer solutions, and hydrogels. Leveraging nature's own effective barrier, mucus, and specifically mimicking mucus' bottlebrush-structured mucins (its core glycoprotein composition) that provide lubrication and hydration, we chemically engineered a mucin-inspired bottlebrush polymer (MIBP) hydrogel. It features zwitterionic polysulfobetaine bottlebrush polymers dynamically crosslinked by ionic interactions with poly(sodium 4-styrenesulfonate). This design enables rapid, injectable gelation and autonomous self-healing, which achieves the similar adaptability of natural mucus. Its superior zwitterionic antifouling properties resist protein and cell adhesion, forming a low-friction, biocompatible barrier. Our work elucidates how the bottlebrush architecture leads to enhanced lubricity and solubility compared to analogous linear polymers, notably by mitigating issues like coacervation. In vivo evaluation in a rat sidewall defect-cecum abrasion model demonstrated anti-adhesion efficacy and biosafety, with mitigated local inflammation. Thus, the MIBP hydrogel, embodying natural, dynamic, and biocompatible barrier principles, offers a highly effective and adaptable strategy to prevent postoperative adhesions and improve surgical outcomes. STATEMENT OF SIGNIFICANCE: Postoperative adhesions are a major surgical complication. Our research introduces a mucin-mimetic hydrogel that replicates the self-healing and lubricating properties of natural mucus. We achieve this using a molecularly engineered bottlebrush polymer that mimics the core architecture of mucin glycoproteins. This unique hydrogel functions as a dynamic barrier, isolating surgical sites and mitigating the physical irritation that causes inflammation, before safely decomposing after treatment. By leveraging this biomimetic design, our material provides a highly effective and adaptable anti-adhesion barrier, offering a significant advance for improving surgical outcomes.