{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:36:03Z","timestamp":1792460163046,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acellular dermal matrix (ADM) scaffolds support tissue regeneration by providing structural integrity, biological cues, and a permissive microenvironment; optimal ADMs integrate with native tissue while preserving extracellular matrix (ECM) composition, microarchitecture, and biomechanics. Decellularization is a critical step in ADM development, as incomplete cellular removal can induce inflammation, whereas excessive chemical treatment can disrupt ECM structure and impair scaffold biofunctionality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we optimized human dermal decellularization to develop ADMs that retain ECM instruction while enabling deep host-cell infiltration and effective recellularization. Two low-detergent protocols were evaluated, Protocol A (sequential hypotonic and hypertonic solutions) and Protocol B (0.1% Triton X-100 in a hypotonic solution), both incorporating controlled ultrasonication and benzonase treatment, and compared with a conventional high-detergent method (Protocol C).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All protocols effectively removed cellular material and nucleic acids, with substantial reductions in residual DNA content; however, Protocols A and B better preserved key ECM proteins, including collagen IV, elastin, and laminin, as confirmed by Raman spectroscopy and scanning electron microscopy. Functional assays demonstrated enhanced fibroblast adhesion and cell proliferation in Protocols A and B, whereas Protocol C showed limited cell growth. In ex vivo human skin wound models, Protocol B supported the highest cell infiltration and ECM deposition by day 21, followed by Protocol A, while Protocol C exhibited minimal integration and remodeling. Histological and immunohistochemical analyses consistently confirmed superior ECM preservation with low-detergent approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, combining controlled ultrasonication with minimal non-ionic detergent exposure represents a promising decellularization strategy that preserves ECM architecture, supports recellularization, and enhances scaffold integration potential for tissue engineering applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1839855","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:10:33Z","timestamp":1786349433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Low-detergent sonication decellularization preserves extracellular matrix architecture and enhances cell infiltration in human acellular dermal matrix"],"prefix":"10.3389","volume":"14","author":[{"given":"Mzwandile","family":"Mbele","sequence":"first","affiliation":[{"name":"Hair and Skin Research Laboratory, MRC-SA Wound Healing Unit, Division of Dermatology, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton\u00e9tha","family":"Jay","sequence":"additional","affiliation":[{"name":"Busamed Paardevlei Private Hospital","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nonhlanhla P.","family":"Khumalo","sequence":"additional","affiliation":[{"name":"Hair and Skin Research Laboratory, MRC-SA Wound Healing Unit, Division of Dermatology, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardeshir","family":"Bayat","sequence":"additional","affiliation":[{"name":"Hair and Skin Research Laboratory, MRC-SA Wound Healing Unit, Division of Dermatology, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1002\/term.3121","article-title":"Biomaterials for breast reconstruction: promises, advances, and challenges","volume":"14","author":"Abdul-Al","year":"2020","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actbio.2008.09.013","article-title":"Extracellular matrix as a biological scaffold material: structure and function","volume":"5","author":"Badylak","year":"2009","journal-title":"Acta Biomater."},{"key":"B3","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1002\/hep.24067","article-title":"The use of whole organ decellularization for the generation of a vascularized liver organoid","volume":"53","author":"Baptista","year":"2011","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s00586-008-0745-3","article-title":"Scaffolding in tissue engineering: general approaches and tissue-specific considerations","author":"Chan","year":"2008","journal-title":"Eur. Spine J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3233","DOI":"10.1016\/j.biomaterials.2011.01.057","article-title":"An overview of tissue and whole organ decellularization processes","volume":"32","author":"Crapo","year":"2011","journal-title":"Biomaterials"},{"key":"B7","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1097\/01.ASW.0000418541.31366.a3","article-title":"Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 2: role of growth factors in normal and pathological wound healing: therapeutic potential and methods of delivery","volume":"25","author":"Demidova-Rice","year":"2012","journal-title":"Adv. Skin. Wound Care"},{"key":"B8","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.actbio.2013.09.006","article-title":"The effect of detergents on the basement membrane complex of a biologic scaffold material","volume":"10","author":"Faulk","year":"2014","journal-title":"Acta Biomater."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3675","DOI":"10.1016\/j.biomaterials.2006.02.014","article-title":"Decellularization of tissues and organs","volume":"27","author":"Gilbert","year":"2006","journal-title":"Biomaterials"},{"key":"B10","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.jdermsci.2013.07.008","article-title":"Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing","volume":"72","author":"Greaves","year":"","journal-title":"J. Dermatol Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/wrr.12029","article-title":"The role of skin substitutes in the management of chronic cutaneous wounds","volume":"21","author":"Greaves","year":"","journal-title":"Wound Repair Regen."},{"key":"B12","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3390\/jfb16100383","article-title":"Acellular extracellular matrix scaffolds in regenerative medicine: advances in decellularization and clinical applications","volume":"16","author":"Jin","year":"2025","journal-title":"J. Funct. Biomater."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1016\/j.biomaterials.2011.10.054","article-title":"Consequences of ineffective decellularization of biologic scaffolds on the host response","volume":"33","author":"Keane","year":"2012","journal-title":"Biomaterials"},{"key":"B14","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ymeth.2015.03.005","article-title":"Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance","volume":"84","author":"Keane","year":"2015","journal-title":"Methods"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.3390\/cells11152439","article-title":"Innovative treatment strategies to accelerate wound healing: trajectory and recent advancements","volume":"11","author":"Kolimi","year":"2022","journal-title":"Cells"},{"key":"B16","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.actbio.2020.03.003","article-title":"Antigen removal process preserves function of small diameter venous valved conduits, whereas SDS-Decellularization results in significant valvular insufficiency","volume":"107","author":"Lopera Higuita","year":"2020","journal-title":"Acta Biomater."},{"key":"B17","doi-asserted-by":"publisher","first-page":"S51","DOI":"10.33549\/physiolres.935045","article-title":"Acellular dermal matrix in plastic and reconstructive surgery","volume":"71","author":"Mihalecko","year":"2022","journal-title":"Physiol. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ymeth.2019.07.005","article-title":"Decellularization and preservation of human skin: a platform for tissue engineering and reconstructive surgery","volume":"171","author":"Milan","year":"2020","journal-title":"Methods"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/polym12092010","article-title":"Scaffolds for wound healing applications","volume":"12","author":"Negut","year":"2020","journal-title":"Polym. (Basel)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"S287","DOI":"10.33549\/physiolres.935185","article-title":"Decellularization techniques of human foreskin for tissue engineering application","volume":"72","author":"Novotna","year":"2023","journal-title":"Physiol. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.ajps.2019.11.008","article-title":"Recent trends on wound management: new therapeutic choices based on polymeric carriers","volume":"15","author":"Okur","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e5821","DOI":"10.1097\/GOX.0000000000005821","article-title":"Absorbable biosynthetic scaffolds in place of silicone for breast reconstruction: a 9-Year experience with 53 patients","volume":"12","author":"Rehnke","year":"2024","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"B23","doi-asserted-by":"publisher","first-page":"230","DOI":"10.3390\/jfb2030230","article-title":"The use of thermal techniques for the characterization and selection of natural biomaterials","volume":"2","author":"Samouillan","year":"2011","journal-title":"J. Funct. Biomater."},{"key":"B24","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e14374","DOI":"10.1111\/iwj.14374","article-title":"Organization of hannover skin bank: sterile culture and procurement protocols for viable cryopreserved allogeneic skin grafts of living donors","volume":"21","author":"Schlottmann","year":"2024","journal-title":"Int. Wound J."},{"key":"B26","doi-asserted-by":"crossref","DOI":"10.1017\/UPO9781922064004.024","article-title":"Principles of wound healing","volume-title":"Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists","author":"Schultz","year":"2011"},{"key":"B27","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1093\/stcltm\/szad046","article-title":"Current challenges and future promise for use of extracellular matrix scaffold to achieve the whole organ tissue engineering moonshot","volume":"12","author":"Somasekhar","year":"2023","journal-title":"Stem Cells Transl. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7756","DOI":"10.1016\/j.biomaterials.2012.07.023","article-title":"Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system","volume":"33","author":"Sullivan","year":"2012","journal-title":"Biomaterials"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1707406","DOI":"10.3389\/fbioe.2025.1707406","article-title":"Advances in 3D-Printed scaffolds for bone defect repair: material strategies and synergistic functional performance","volume":"13","author":"Tang","year":"2025","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2147\/BSAM.S115187","article-title":"Current insights into skin banking: storage, preservation and clinical importance of skin allografts","volume":"5","author":"Tognetti","year":"2017","journal-title":"J. Biorepository Sci. Appl. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.actbio.2016.12.033","article-title":"The impact of detergents on the tissue decellularization process: a ToF-SIMS study","volume":"50","author":"White","year":"2017","journal-title":"Acta Biomater."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1016\/j.actbio.2014.01.028","article-title":"Immunogenicity in xenogeneic scaffold generation: antigen removal vs. decellularization","volume":"10","author":"Wong","year":"2014","journal-title":"Acta Biomater."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.03.024","article-title":"In vivo xenogeneic scaffold fate is determined by residual antigenicity and extracellular matrix preservation","volume":"92","author":"Wong","year":"2016","journal-title":"Biomaterials"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1016\/j.biomaterials.2009.11.088","article-title":"Impact of heart valve decellularization on 3-D ultrastructure, immunogenicity and thrombogenicity","volume":"31","author":"Zhou","year":"2010","journal-title":"Biomaterials"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1839855\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:10:34Z","timestamp":1786349434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1839855\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":33,"alternative-id":["10.3389\/fbioe.2026.1839855"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2026.1839855","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1839855"}}