P0155 Investigating the effect of a novel bio-based tissue glue for Perianal Fistulas in Crohn's Disease: A Low-Cost Rodent model study

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Abstract Background Perianal fistulas (PAFs) are a severe complication of Crohn’s disease (CD) significantly affecting quality of life with limited treatment options. TNBS-induced colitis rodent models to study CD-PAF is costly and time-intensive. This study aimed to study the efficacy of a novel decellularized dermal extracellular matrix (ddECM) derived from goat skin as a tissue glue 1 for PAF treatment in a low-cost acetic-acid induced CD-PAF rodent model. Methods Two fistula tracts (0.3mm,1.3mm from the anal sphincter) were created in 12 male Wistar rats (aged 8-10weeks, body weight 180-220g); and a seton was placed to keep them open(Fig1A) 2. 500µL of 5%(v/v)acetic acid was injected biweekly intrarectally for a week to induce colitis and fistula discharge . Ultrasound (USG), in vivo imaging (IVIS) using indocyanine green fluorescent dye, and histopathology were used to assess inflammation and fistula formation(Fig2). 1ml bio-based tissue glue was applied to occlude each of the orifices and polymerized with UV light for 30-seconds. Rats were monitored for one week post glue treatment with single doze of 5% acetic acid as maintenance. USG was repeated to confirm healing. Upon sacrifice, tissue was collected for histopathology examination to confirm the success of CD-PAF and healing. Results All rats exhibited soft feces, diarrhoea, widening of fistula orifice, purulent fistula discharge, blood per rectum and significant weight loss after induction(Fig1B). USG confirmed active inflammation revealing edematous fistula tracts on both sides. This was validated by strong fluorescent signal in IVIS at the site of inflammation. Histopathology staining also showed acute inflammation (Fig2). One rat died post-induction. Tissue glue was applied to the remaining 11 rats. Upon one week follow-up, 10 of 11 rats exhibited normal feces, closure of fistula, absence of purulent fistula discharge and weight gain. USG and histopathology showed complete fistula healing in 10 rats and partial healing in one. Conclusion This study has demonstrated the use of low-cost CD-PAF rodent model which offers a faster induction (1-week) than conventional TNBS models (8 weeks). The novel bio-based tissue glue has shown to be a feasible and an effective treatment for CD-PAFs. References 1. Bera, A.K. et al. BioScience.2022 2. Ling Li et al. Sci. Adv. 2023 3. Singh A. et al. Inflamm Bowel Dis. 2023

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