The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation
The rising incidence of colorectal cancer and ulcerative colitis underscores an urgent need for regenerative solutions to address functional deficits after colectomy. However, the creation of clinically applicable large intestine scaffolds remains underdeveloped. Here, we report the successful gener...
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MDPI AG
2025-05-01
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| author | Murali Somasundaram Karin V. Greco Gauraang Bhatnagar Simon Gabe Paul Sibbons Peter Friend Tahera Ansari |
| author_facet | Murali Somasundaram Karin V. Greco Gauraang Bhatnagar Simon Gabe Paul Sibbons Peter Friend Tahera Ansari |
| author_sort | Murali Somasundaram |
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| description | The rising incidence of colorectal cancer and ulcerative colitis underscores an urgent need for regenerative solutions to address functional deficits after colectomy. However, the creation of clinically applicable large intestine scaffolds remains underdeveloped. Here, we report the successful generation and thorough characterisation of transplantable-sized porcine large intestinal scaffolds via perfusion decellularisation. This method effectively preserved extracellular matrix (ECM) structural and biochemical integrity while minimising immunogenicity through cellular component removal. Crucially, native vasculature remained intact, confirmed by histology, DNA quantification, and high-resolution CT angiography. Despite efficient decellularisation, challenges including residual nucleic acids, ECM heterogeneity, and partial microvascular occlusion were noted, echoing ongoing limitations in engineered, perfusable, full-thickness scaffolds. In vivo implantation demonstrated favourable biocompatibility and host integration; however, thrombosis occurred due to the lack of pre-seeded cells, emphasising the necessity of recellularisation for functional perfusion prior to implantation. This study addresses significant field limitations, presenting the first reproducible approach for structurally intact, perfusable, full-thickness large intestinal scaffolds of transplantable dimensions. Our innovations offer a strong foundation for future integration of patient-derived cells, stem cells, and organoids, progressing toward clinically viable, scalable, tissue-engineered large intestine constructs, from xenogeneic sources, relevant for regenerative medicine, disease modelling, and pharmacological screening. |
| format | Article |
| id | doaj-art-c35010a26679488392f3f2f07040b372 |
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| issn | 2073-4409 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-c35010a26679488392f3f2f07040b3722025-08-20T02:32:52ZengMDPI AGCells2073-44092025-05-01141181710.3390/cells14110817The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion DecellularisationMurali Somasundaram0Karin V. Greco1Gauraang Bhatnagar2Simon Gabe3Paul Sibbons4Peter Friend5Tahera Ansari6Research and Development Department, Northwick Park Institute for Medical Research—The Griffin Institute, London HA1 3UJ, UKResearch and Development Department, Northwick Park Institute for Medical Research—The Griffin Institute, London HA1 3UJ, UKDepartment of Radiology, St Mark’s Hospital and Academic Institute, London NW10 7NS, UKLennard-Jones Intestinal Failure Unit, St Mark’s Hospital and Academic Institute, London NW10 7NS, UKResearch and Development Department, Northwick Park Institute for Medical Research—The Griffin Institute, London HA1 3UJ, UKNuffield Department of Surgical Sciences, Oxford Transplant Centre, University of Oxford, Oxford OX1 4BH, UKResearch and Development Department, Northwick Park Institute for Medical Research—The Griffin Institute, London HA1 3UJ, UKThe rising incidence of colorectal cancer and ulcerative colitis underscores an urgent need for regenerative solutions to address functional deficits after colectomy. However, the creation of clinically applicable large intestine scaffolds remains underdeveloped. Here, we report the successful generation and thorough characterisation of transplantable-sized porcine large intestinal scaffolds via perfusion decellularisation. This method effectively preserved extracellular matrix (ECM) structural and biochemical integrity while minimising immunogenicity through cellular component removal. Crucially, native vasculature remained intact, confirmed by histology, DNA quantification, and high-resolution CT angiography. Despite efficient decellularisation, challenges including residual nucleic acids, ECM heterogeneity, and partial microvascular occlusion were noted, echoing ongoing limitations in engineered, perfusable, full-thickness scaffolds. In vivo implantation demonstrated favourable biocompatibility and host integration; however, thrombosis occurred due to the lack of pre-seeded cells, emphasising the necessity of recellularisation for functional perfusion prior to implantation. This study addresses significant field limitations, presenting the first reproducible approach for structurally intact, perfusable, full-thickness large intestinal scaffolds of transplantable dimensions. Our innovations offer a strong foundation for future integration of patient-derived cells, stem cells, and organoids, progressing toward clinically viable, scalable, tissue-engineered large intestine constructs, from xenogeneic sources, relevant for regenerative medicine, disease modelling, and pharmacological screening.https://www.mdpi.com/2073-4409/14/11/817tissue-engineered large intestine (TELI)porcine modelin vivofull-thickness large intestinal scaffoldsperfusable native vasculaturexenogeneic source |
| spellingShingle | Murali Somasundaram Karin V. Greco Gauraang Bhatnagar Simon Gabe Paul Sibbons Peter Friend Tahera Ansari The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation Cells tissue-engineered large intestine (TELI) porcine model in vivo full-thickness large intestinal scaffolds perfusable native vasculature xenogeneic source |
| title | The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation |
| title_full | The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation |
| title_fullStr | The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation |
| title_full_unstemmed | The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation |
| title_short | The Development and Characterisation of A Porcine Large Intestinal Biological Scaffold by Perfusion Decellularisation |
| title_sort | development and characterisation of a porcine large intestinal biological scaffold by perfusion decellularisation |
| topic | tissue-engineered large intestine (TELI) porcine model in vivo full-thickness large intestinal scaffolds perfusable native vasculature xenogeneic source |
| url | https://www.mdpi.com/2073-4409/14/11/817 |
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