Search

Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.

Zwitterionic polymers have shown promising results in non-fouling and preventing thrombosis. However, the lack of controlled surface coverage hinders their application for biomedical devices. Inspired by the natural biological surfaces, a facile zwitterionic microgel-based coating strategy is developed by the co-deposition of poly (sulfobetaine methacrylate-co-2-aminoethyl methacrylate) microgel (SAM), polydopamine (PDA), and sulfobetaine-modified polyethyleneimine (PES). The SAMs were used to construct controllable morphology by using the PDA combined with PES (PDAS) as the intermediate layer, which can be easily modulated via adjusting the crosslinking degree and contents of SAMs. The obtained SAM/PDAS coatings exhibit high anti-protein adhesive properties and can effectively inhibit the adhesion of cells, bacteria, and platelet through the synergy of high deposition density and controllable morphology. In addition, the stability of SAM/PDAS coating is improved owing to the anchoring effects of PDAS to substrate and SAMs. Importantly, the ex vivo blood circulation test in rabbits suggests that the SAM/PDAS coating can effectively decrease thrombosis without anticoagulants. This study provides a versatile coating method to address the integration of zwitterionic microgel-based coatings with high deposition density and controllable morphology onto various substrates for wide biomedical device applications. STATEMENT OF SIGNIFICANCE: Thrombosis is a major cause of medical device implantation failure, which results in significant morbidity and mortality. In this study, inspired by natural biological surfaces (fish skin and vascular endothelial layer) and the anchoring ability of mussels, we report a convenient and efficient method to firmly anchor zwitterionic microgels using an oxidative co-deposition strategy. The prepared coating has excellent antifouling and antithrombotic properties through the synergistic effect of physical morphology and chemical composition. This biomimetic surface engineering strategy is expected to provide new insights into the clinical problems of blood-contacting devices related to thrombosis.

Postoperative adhesions are very common complications after general abdominal surgery. Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. The prevention of recurrent adhesion after adhesiolysis is more difficult because the injury is more severe and adhesion mechanism is more complicated compared with the primary adhesion. In this study, a thermoresponsive hydrogel contained galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC) was developed as a barrier device for recurrent adhesion prevention after adhesiolysis due to its injectability and spontaneous gelling behaviors at the body temperature without any chemical reactions or extra driving factors. First, mXG and HBC were synthesized via enzymatic modification and etherification reaction, respectively. Rheological measurements indicated that the mXG/HBC composite system showed excellent thermosensitivity properties, and their gelation temperature and time can be modulated via adjusting the mXG/HBC ratio. Moreover, the mXG/HBC hydrogel exhibited excellent cytocompatibility and hemocompatibility in vitro. Furthermore, the mXG/HBC hydrogel could promote wound healing in the rat skin wound model. Finally, the efficacy of the mXG/HBC composite hydrogel in the prevention of recurrent adhesion was evaluated in a more rigorous rat repeated-injury adhesion model. The results demonstrated that the composite hydrogel could not only effectively prevent recurrent adhesion after adhesiolysis, but also promote wound healing and reduce scare formation. These results suggested that the mXG/HBC composite hydrogel may be a promising candidate as an injectable anti-adhesion system for clinical applications. Statement of Significance Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. So far, most of the existing barrier systems and pharmacological approaches were developed for primary adhesion prevention while few attention has paid on prevention of recurrent adhesion after adhesiolysis. In the present study, we developed a thermoresponsive polysaccharide-based composite hydrogel by simple mixing galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC). The resulting mXG/HBC composite hydrogel not only was easy to handle and highly effective in preventing the recurrent adhesion after adhesiolysis, but also could promote wound healing and reduce scare formation. Our study provide an effective anti-adhesion system for preventing recurrent adhesion after adhesiolysis.

Peritoneal adhesion is very common after abdominal and pelvic surgery, which leads to a variety of severe complications. Although numerous pharmacological treatments and barrier-based devices have been investigated to minimize or prevent postoperative adhesion, the clinical efficacy is not very encouraging. In this work, a biodegradable and thermoreversible galactose modified xyloglucan (mXG) hydrogel was developed and the efficacy of mXG hydrogel in preventing postoperative peritoneal adhesion was investigated. The 4% (w/v) mXG solution was a free flowing sol at low temperature, but could rapidly convert into a physical hydrogel at body temperature without any extra additives or chemical reactions. In vitro cell tests showed that mXG hydrogel was non-toxic and could effectively resist the adhesion of fibroblasts. Moreover, in vitro and in vivo degradation experiments exhibited that mXG hydrogel was degradable and biocompatible. Finally, the rat model of sidewall defect-cecum abrasion was employed to evaluate the anti-adhesion efficacy of the mXG hydrogel. The results demonstrated that mXG hydrogel could effectively prevent postoperative peritoneal adhesion without side effects. The combination of suitable gel temperature, appropriate biodegradation period, and excellent postoperative anti-adhesion efficacy make mXG hydrogel a promising candidate for the prevention of postsurgical peritoneal adhesion. Statement of significance Despite numerous drugs or barrier-based devices have been developed to prevent postoperative adhesion, few solutions have proven to be uniformly effective in subsequent clinical trials. In the present study, we developed a biodegradable and thermoreversible galactose modified xyloglucan (mXG) hydrogel by green enzymatic reaction without using any organic reagents. The developed physical mXG hydrogel not only showed excellent injectability, appropriate gelation time and temperature, but also exhibited excellent biocompatibility and biodegradability both in vitro and in vivo. In addition, mXG hydrogel was easy to handle and could effectively prevent postoperative adhesion without side effects in a rat model of sidewall defect-bowel abrasion. Our study provide a safe and effective postoperative anti-adhesion material which may have potential applications in clinical practice.