Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease

Abstract

Background and Aims The Self-assembling Peptide Hydrogel (SAPH, PuraMatrix TM), a fully synthetic peptide solution designed to replace collagen, has recently been used to promote mucosal regeneration in iatrogenic ulcers following endoscopic submucosal dissection. Herein, we evaluated its utility in ulcer repair using a rat model of topical trinitrobenzene sulfonic acid (TNBS)-induced colonic injuries. Methods Colonic injuries were generated in 7-week-old rats by injecting an ethanol solution (35%, 0.2 mL) containing 0.15 M TNBS into the colonic lumen. At 2- and 4-days post-injury, the rats were subjected to endoscopy, and SAPH (or vehicle) was topically applied to the ulcerative lesion. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to detect SAPH. Colonic expression of cytokines and wound healing-related factors were assessed using real-time polymerase chain reaction or immunohistochemistry. Results SAPH treatment significantly reduced ulcer length (P = 0.0014) and area (P = 0.045), while decreasing colonic weight (P = 0.0375) and histological score (P = 0.0005) 7 days after injury. SAPH treatment also decreased colonic expression of interleukin (IL)-1α (P = 0.0233) and IL-6 (P = 0.0343) and increased that of claudin-1 (P = 0.0486), villin (P = 0.0183), and β-catenin staining (P = 0.0237). TOF-SIMS revealed lesional retention of SAPH on day 7 post-injury. Furthermore, SAPH significantly promoted healing in in vivo mechanical intestinal wound models. Conclusions SAPH application effectively suppressed colonic injury, downregulated inflammatory cytokine expression, and upregulated wound healing-related factor expression in the rat model; thus, it may represent a promising therapeutic strategy for IBD-related colonic ulcers.

GelNB molecular coating as a biophysical barrier to isolate intestinal irritating metabolites and regulate intestinal microbial homeostasis in the treatment of inflammatory bowel disease

“…We chose continuous observation for one week after TNBS induction as the time window for evaluation as studies have shown that injury can completely disappear on day 7 after TNBS, making it difficult to compare efficacy among groups [ 58 ]. As such, an observation time of seven days was considered to be optimal.…”

Clinical Use of the Self-Assembling Peptide RADA16: A Review of Current and Future Trends in Biomedicine

“…Purposefully created periodontal defects in rats showed significant healing and bone regeneration at 4 weeks when defects were initially filled with 2.5% RADA16 solution compared to defects filled with Matrigel (a mouse-derived ECM-like product) or left unfilled ( Takeuchi et al, 2016 ). In a rat model of inflammatory colitis simulated by chemically induced colon mucosal ulceration, topical application of 1% RADA16 (as PuraMatrix) significantly suppressed colonic injury as viewed by endoscopy, downregulated expression of inflammatory cytokines, and increased expression of wound-healing factors ( Araki et al, 2021 ). Topical application of RADA16 in an assessor-blinded porcine EMR study suggested enhanced neomucosal coverage and less submucosal damage with RADA16 versus no-RADA16 treatment, at 6 days after lesion creation ( Tsiamoulos et al, 2017 ).…”

Cell and Tissue Imaging by TOF-SIMS and MALDI-TOF: An Overview for Biological and Pharmaceutical Analysis

“…Brain mouse sections Monitor spatial distribution of lipids (cholesterol, sulfatides, phosphatidylinositols, and phosphatidylcholines). with a cluster ion beam Bi 3 + 10 keV, was used first to detect SAPH in rat models suffering from colonic injuries, and second to prove that SAPH is a propitious therapeutic approach for inflammatory bowel diseases, especially colonic ulcers (Araki et al, 2021). Earlier in the same year, Wenli et al investigated the spatiotemporal localization of lipid metabolites to identify potential biomarkers and to understand atherosclerosis (AS) pathology.…”