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Volume 19
Issue 9
10.3390/ma19091803
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Article

Benchmarking of Decellularization Protocols for Small Intestinal Submucosa: Defining the Gold Standard for Functional Tissue Engineering

by
Carlos Adams
1,2,†,
Iván Gómez
1,†,
Odin Rodríguez
1,
Alexey Vigil
2,
Cecilio Hernández
3,
Jorge Ceballos
3,
Bruno A. Cisterna
4 and
Diego Reginensi
1,2,3,5,*
1
Regenerative Therapies, Faculty of Biosciences and Public Health, Universidad Especializada de las Américas (UDELAS), Panama City 0849-0141, Panama
2
Regenerative Therapies, Interdisciplinary Center for Research in Life and Health Sciences (CIVSAL), Faculty of Health Science and Engineering, Universidad Latina de Panama (ULATINA), Panama City 0849-0141, Panama
3
Doctorate Program in Biosciences and Biotechnology, Faculty of Sciences and Technology, Universidad Tecnológica de Panama (UTP), Panama City 0849-0141, Panama
4
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
5
Center for Biodiversity and Drug Discovery, Institute of Scientific Research and High Technology Services of Panama (INDICASAT-AIP), City of Knowledge, Panama City 0843-01103, Panama
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Materials 2026, 19(9), 1803; https://doi.org/10.3390/ma19091803
Submission received: 30 March 2026 / Revised: 22 April 2026 / Accepted: 23 April 2026 / Published: 28 April 2026
(This article belongs to the Special Issue ECM-Mimetic Biomaterials for Tissue Engineering)
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Abstract

The fabrication of decellularized small intestinal submucosa (dSIS) requires a precise balance between effective cellular removal and the preservation of structural integrity. In this study, we compared four published dSIS protocols representing detergent-based, chaotropic-salt-based, and sequential ionic/alkaline–acidic strategies. Their performance was evaluated based on residual DNA, collagen preservation, surface ultrastructure, and mechanical properties. The best decellularization protocol demonstrated the lowest residual DNA levels, together with better collagen retention, scaffold architecture, and mechanical performance than the other methods tested. The selected decellularized scaffold was used in a murine acute wound model and showed good biocompatibility and integration with the surrounding tissue at 10 days after implantation. However, further extensive testing in murine models is essential before future scaling. Finally, this comparative study provides a practical framework for selecting dSIS preparation methods for skin repair applications.
Keywords: Small Intestinal Submucosa (SIS); decellularization strategy; ECM scaffold; biomimetic materials; skin repair; wound healing; tissue engineering Small Intestinal Submucosa (SIS); decellularization strategy; ECM scaffold; biomimetic materials; skin repair; wound healing; tissue engineering
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MDPI and ACS Style

Adams, C.; Gómez, I.; Rodríguez, O.; Vigil, A.; Hernández, C.; Ceballos, J.; Cisterna, B.A.; Reginensi, D. Benchmarking of Decellularization Protocols for Small Intestinal Submucosa: Defining the Gold Standard for Functional Tissue Engineering. Materials 2026, 19, 1803. https://doi.org/10.3390/ma19091803

AMA Style

Adams C, Gómez I, Rodríguez O, Vigil A, Hernández C, Ceballos J, Cisterna BA, Reginensi D. Benchmarking of Decellularization Protocols for Small Intestinal Submucosa: Defining the Gold Standard for Functional Tissue Engineering. Materials. 2026; 19(9):1803. https://doi.org/10.3390/ma19091803

Chicago/Turabian Style

Adams, Carlos, Iván Gómez, Odin Rodríguez, Alexey Vigil, Cecilio Hernández, Jorge Ceballos, Bruno A. Cisterna, and Diego Reginensi. 2026. "Benchmarking of Decellularization Protocols for Small Intestinal Submucosa: Defining the Gold Standard for Functional Tissue Engineering" Materials 19, no. 9: 1803. https://doi.org/10.3390/ma19091803

APA Style

Adams, C., Gómez, I., Rodríguez, O., Vigil, A., Hernández, C., Ceballos, J., Cisterna, B. A., & Reginensi, D. (2026). Benchmarking of Decellularization Protocols for Small Intestinal Submucosa: Defining the Gold Standard for Functional Tissue Engineering. Materials, 19(9), 1803. https://doi.org/10.3390/ma19091803

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