Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches

International Journal of Molecular Sciences

卷:23

Massimo Marchesan¹  Ilaria Toniolo²  Emanuele Luigi Carniel²  Giulia Borile³  Martina Casarin⁴  Alessandro Morlacco⁴  Fabrizio Dal Moro⁴  Deborah Sandrin⁵  Tiago Moderno Fortunato⁵  Gino Gerosa⁵  Saima Imran⁵  Filippo Romanato⁵  Andrea Bagno⁵  Martina Todesco⁵ 

[1] Consultant of Animal Welfare and Food Inspection, 35100 Padua, Italy;

[2] Department of Industrial Engineering, University of Padua, via Marzolo 9, 35131 Padua, Italy;

[3] Department of Physics and Astronomy ‘G. Galilei’, University of Padova, via Marzolo 8, 35131 Padua, Italy;

[4] Department of Surgery, Oncology and Gastroenterology, Giustiniani 2, 35128 Padua, Italy;

[5] L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, via N. Giustiniani 2, 35128 Padua, Italy;

关键词: small intestinal submucosa;    decellularization;    urinary diversions;    regenerative medicine;    tissue engineering;    biomaterial;   

DOI  :  10.3390/ijms23052826

来源: DOAJ

【 摘 要 】

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

【 授权许可】

Unknown