Tissue engineering is a promising field for treating various diseases using tissue-like structures generated through biomaterials, scaffolds, nanoparticles, biomolecules, and stem cells. This advanced method is considered one of the next-generation therapeutic techniques that may solve the therapeutic challenges in treating perianal fistula based on seton therapy. Remarkable advances in stem cell biology, genetics, biomaterials, fabrication technologies, and nanotechnology have provided the opportunity to implement this multidisciplinary approach to repair damaged tissue in the seton-based fistula treatment. In addition, tissue engineering provides us with nanostructured biomaterials to fabricate setons that can act as scaffolds, with modified mechanical and biological properties such as antibacterial and anti-inflammatory. This review focuses on the applications, advantages, and future perspectives of tissue engineering to enhance the seton placement techniques and present a novel therapeutic solution to treat perianal fistula. In addition, in vivo and in vitro studies about implementing tissue engineering in the treatment of perianal fistula are reported in this study. Also, it summarizes the surgical procedures for the treatment of fistula, including Ligation of the Intersphincteric Fistula Tract (LIFT), Fistula Laser Closure (FiLaC™), Over-The-Scope Clip System (OTSC), Video-assisted anal fistula treatment (VAAFT), Anal fistula plug (AFP), and Rectal advancement flap (RAF). Furthermore, the applications and properties of different setons including, cutting setons (Penrose drains, rubber band, polypropylene, and silk), non-cutting setons (loose, knot-free, Comfort, and Super Seton®), and chemical setons (Ksharasutra) are described. In the end, we present the challenges and future trends of implementing tissue engineering technology in the seton-based therapy for the treatment of perianal fistula. The applications of tissue engineering in seton-based fistula therapy. The scaffolds with controllable mechanical properties and degradation rate can have antibacterial, anti-inflammatory, and drug-releasing properties. Besides, the scaffolds can be incorporated or covered with stem cells to regenerate damaged tissues in the perianal fistula site.
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