Cited by 58Tissue Engineering and Regenerative MedicineBone Tissue Engineering MaterialsElectrospun Nanofibers in Biomedical Applications

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

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Casarin, Martina, Fortunato, Tiago Moderno, Imran, Saima, Todesco, Martina, Sandrin, Deborah, Borile, Giulia, Toniolo, Ilaria, Marchesan, Massimo +6 more·2022·International Journal of Molecular Sciences

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.

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  • US FDA allows unrestricted presence of DNA in biological scaffolds.

    “However, the residual DNA within dECM cannot elicit rejection in the absence of immunogenic adjuvants [57], and US Federal Drug Administration allows the unrestricted presence of DNA in biological scaffolds [58].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [58]

    The Discussion states that the U.S. Federal Drug Administration does not set limits for DNA in biologic scaffolds. That supports the absence of a specified DNA limit, but not the stronger claim that it affirmatively allows unrestricted DNA presence; the same passage calls for studies to determine an acceptable threshold. No page number is provided in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
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.
Affiliations
  • University of Padua (IT)
  • Consultant of Animal Welfare and Food Inspection, 35100 Padua, Italy
  • Department of Surgery, Oncology and Gastroenterology, Giustiniani 2, 35128 Padua, Italy
Corresponding author
Morlacco, Alessandro
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-03-04
Volume
23
Issue
5
Pages
2826
ISSN
1422-0067 (ISSN-L)
OpenAlex
W4220836644
Cited by
58
References
4
Citations by year
2026: 11 · 2025: 11 · 2024: 14 · 2023: 14 · 2022: 8
FWCI
11.23
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
Consorzio per la Ricerca Sanitaria (DGR1017, 17 July 2018)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
Keywords
small intestinal submucosa, decellularization, Tergitol, bladder cancer, radical cystectomy, urinary diversion, extracellular matrix, tissue mechanics, cytocompatibility, human fibroblasts
MeSH terms
Animals, Urinary Bladder Neoplasms, DNA, Humans, Intestinal Mucosa, Intestine, Small, Quality of Life, Swine, Tissue Engineering

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