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Article

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

by
Martina Casarin
1,2,
Tiago Moderno Fortunato
2,3,
Saima Imran
2,3,
Martina Todesco
2,4,
Deborah Sandrin
2,5,
Giulia Borile
5,6,
Ilaria Toniolo
4,
Massimo Marchesan
7,
Gino Gerosa
2,3,
Andrea Bagno
2,4,
Filippo Romanato
2,5,6,
Emanuele Luigi Carniel
4,
Alessandro Morlacco
1,2,* and
Fabrizio Dal Moro
1,2
1
Department of Surgery, Oncology and Gastroenterology, Giustiniani 2, 35128 Padua, Italy
2
L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, via N. Giustiniani 2, 35128 Padua, Italy
3
Department of Cardiac, Thoracic Vascular Sciences and Public Health, University of Padua, via Giustiniani 2, 35128 Padua, Italy
4
Department of Industrial Engineering, University of Padua, via Marzolo 9, 35131 Padua, Italy
5
Department of Physics and Astronomy ‘G. Galilei’, University of Padova, via Marzolo 8, 35131 Padua, Italy
6
Laboratory of Optics and Bioimaging, Institute of Pediatric Research Città della Speranza, 35127 Padua, Italy
7
Consultant of Animal Welfare and Food Inspection, 35100 Padua, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(5), 2826; https://doi.org/10.3390/ijms23052826
Submission received: 13 February 2022 / Revised: 27 February 2022 / Accepted: 1 March 2022 / Published: 4 March 2022
(This article belongs to the Special Issue Optimization of Biomaterials for Reconstructive and Regenerative Medicine)
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Abstract

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.
Keywords: small intestinal submucosa; decellularization; urinary diversions; regenerative medicine; tissue engineering; biomaterial small intestinal submucosa; decellularization; urinary diversions; regenerative medicine; tissue engineering; biomaterial

Share and Cite

MDPI and ACS Style

Casarin, M.; Fortunato, T.M.; Imran, S.; Todesco, M.; Sandrin, D.; Borile, G.; Toniolo, I.; Marchesan, M.; Gerosa, G.; Bagno, A.; et al. 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. Int. J. Mol. Sci. 2022, 23, 2826. https://doi.org/10.3390/ijms23052826

AMA Style

Casarin M, Fortunato TM, Imran S, Todesco M, Sandrin D, Borile G, Toniolo I, Marchesan M, Gerosa G, Bagno A, et al. 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. 2022; 23(5):2826. https://doi.org/10.3390/ijms23052826

Chicago/Turabian Style

Casarin, Martina, Tiago Moderno Fortunato, Saima Imran, Martina Todesco, Deborah Sandrin, Giulia Borile, Ilaria Toniolo, Massimo Marchesan, Gino Gerosa, Andrea Bagno, and et al. 2022. "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 23, no. 5: 2826. https://doi.org/10.3390/ijms23052826

APA Style

Casarin, M., Fortunato, T. M., Imran, S., Todesco, M., Sandrin, D., Borile, G., Toniolo, I., Marchesan, M., Gerosa, G., Bagno, A., Romanato, F., Carniel, E. L., Morlacco, A., & Dal Moro, F. (2022). 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, 23(5), 2826. https://doi.org/10.3390/ijms23052826

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