Dataset Information

Light-Operated Transient Unilateral Adhesive Hydrogel for Comprehensive Prevention of Postoperative Adhesions.

ABSTRACT: Dislocation of anti-adhesion materials, non-specific tissue adhesion, and the induction of secondary fibrinolysis disorders are the main challenges faced by postoperative anti-adhesion materials. Herein, a self-leveling transient unilateral adhesive hydrogel is custom-designed to conquer these challenges with a theoretically calculated and dual-step tailored gellan gum (GG) as the sole agent. First, the maximum gelation temperature of GG is lowered from 42-25 °C through controlled perturbation of intra- and inter-molecular hydrogen bonds, which is achieved by employing the methacrylic anhydride as a "hydrogen bond's perturbator" to form methacrylate GG (MeGG). Second, the "self-leveling" injectability and wound shape adaptably are endowed by the formation of borate-diol complexed MeGG (BMeGG). Finally, the transient unilateral tissue-adhesive hydrogel (BMeGG-H) barrier is prepared through photo-controlled cross-linking of reactive alkenyl groups. This degradable hydrogel demonstrates favorable rheological properties, light-controlled unilateral adhesion properties, biocompatibility, anti-fibrin adhesion, and anti-cell adhesion properties in vitro. Comprehensive regulation of the fibrinolysis balance toward non-adhesion is conformed in a rat model after intra-abdominal surgery via anti-autoinflammatory response, intestinal wall integrity repair, and Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) balance adjustment. Notably, the 14^th day anti-adhesion effective rate is 100%, indicating its significant potential in clinical applications for postoperative anti-adhesion.

SUBMITTER: Cui F

PROVIDER: S-EPMC11348232 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Light-Operated Transient Unilateral Adhesive Hydrogel for Comprehensive Prevention of Postoperative Adhesions.

Cui Furong F Shen Shihong S Ma Xiaoxuan X Fan Daidi D

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240625 32

Dislocation of anti-adhesion materials, non-specific tissue adhesion, and the induction of secondary fibrinolysis disorders are the main challenges faced by postoperative anti-adhesion materials. Herein, a self-leveling transient unilateral adhesive hydrogel is custom-designed to conquer these challenges with a theoretically calculated and dual-step tailored gellan gum (GG) as the sole agent. First, the maximum gelation temperature of GG is lowered from 42-25 °C through controlled perturbation o ...[more]

PMID: 38924679

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Project description:Postoperative adhesions protect, repair, and supply nutrients to injured tissues; however, such adhesions often remain permanent and complicate otherwise successful surgeries by tethering tissues together that are normally separated. An ideal adhesion barrier should not only effectively prevent unwanted adhesions but should be easy to use, however, those that are currently available have inconsistent efficacy and are difficult to handle or to apply. A robust hydrogel film composed of alginate and a photo-crosslinkable hyaluronic acid (HA) derivative (glycidyl methacrylate functionalized hyaluronic acid (GMHA)) represents a solution to this problem. A sacrificial porogen (urea) was used in the film manufacture process to impart macropores that yield films that are more malleable and tougher than equivalent films produced without the sacrificial porogen. The robust mechanical behavior of these templated alginate/GMHA films directly facilitated handling characteristics of the barrier film. In a rat peritoneal abrasion model for adhesion formation, the polysaccharide films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion technology on the market, Seprafilm®. STATEMENT OF SIGNIFICANCE: Postoperative adhesions often remain permanent and complicate otherwise successful surgeries by tethering tissues together that are normally separated and pose potentially significant challenges to patients. Therefore, the generation of adhesion barriers that are easy to deploy during surgery and effectively prevent unwanted adhesions is a big challenge. In this study robust hydrogel films composed of alginate and a photo-crosslinkable hyaluronic acid (HA) derivative (glycidyl methacrylate functionalized HA, GMHA) were fabricated and investigated for their potential to act as a solution to this problem using a rat peritoneal abrasion model for adhesion formation. We observed the polysaccharide films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion technology on the market, Seprafilm®, suggesting that such films represent a promising strategy for the prevention of postoperative adhesions.

Project description:Formation of asymmetric, rigid scar tissue known as surgical adhesions is caused by traumatic disruption of mesothelial-lined surfaces in surgery. A widely adopted prophylactic barrier material (Seprafilm) for the treatment of intra-abdominal adhesions is applied operatively as a pre-dried hydrogel sheet but has reduced translational efficacy due its brittle mechanical properties. Topically administered peritoneal dialysate (Icodextrin) and anti-inflammatory drugs have failed to prevent adhesions due to an uncontrolled release profile. Hence, inclusion of a targeted therapeutic into a solid barrier host matrix with improved mechanical properties could provide dual utility in adhesion prevention and as a surgical sealant. Spray deposition of poly(lactide-co-caprolactone) (PLCL) polymer fibers through solution blow spinning has yielded a tissue-adherent barrier material with previously reported adhesion prevention efficacy due to a surface erosion mechanism that inhibits deposition of inflamed tissue. However, such an approach uniquely presents an avenue for controlled therapeutic release through mechanisms of diffusion and degradation. Such a rate is kinetically tuned via facile blending of "high" molecular weight (HMW) and "low" molecular weight (LMW) PLCL with slow and fast biodegradation rates, respectively. Here, we explore viscoelastic blends of HMW PLCL (70% w/v) and LMW PLCL (30% w/v) as a host matrix for anti-inflammatory drug delivery. In this work, COG133, an apolipoprotein E (ApoE) mimetic peptide with potent anti-inflammatory properties was selected and tested. In vitro studies with PLCL blends presented low (∼30%) and high (∼80%) percent release profiles over a 14-day period based on the nominal molecular weight of the HMW PLCL component. Two independent mouse models of cecal ligation and cecal anastomosis significantly reduced adhesion severity versus Seprafilm, COG133 liquid suspension, and no treatment control. The synergy of physical and chemical methods in a barrier material with proven preclinical studies highlights the value of COG133-loaded PLCL fiber mats in effectively dampening the formation of severe abdominal adhesions.

Dataset Information

Light-Operated Transient Unilateral Adhesive Hydrogel for Comprehensive Prevention of Postoperative Adhesions.

Publications

Light-Operated Transient Unilateral Adhesive Hydrogel for Comprehensive Prevention of Postoperative Adhesions.

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