Consequences of ineffective decellularization of biologic scaffolds on the host response
Abstract
Biologic scaffold materials composed of extracellular matrix (ECM) are routinely used for a variety of clinical applications. Despite known variations in tissue remodeling outcomes, quantitative criteria by which decellularization can be assessed were only recently described and as a result, the amount of retained cellular material varies widely among commercial products. The objective of this study was to evaluate the consequences of ineffective decellularization on the host response. Three different methods of decellularization were used to decellularize porcine small intestinal ECM (SIS-ECM). The amount of cell remnants was quantified by the amount and fragmentation of DNA within the scaffold materials. The M1/M2 phenotypic polarization profile of macrophages, activated in response to these ECM scaffolds, was assessed in vitro and in vivo using a rodent model of body wall repair. The results show that, in vitro, more aggressive decellularization is associated with a shift in macrophage phenotype predominance from M1 to M2. While this shift was not quantitatively apparent in vivo, notable differences were found in the distribution of M1 vs. M2 macrophages within the various scaffolds. A clear association between macrophage phenotype and remodeling outcome exists and effective decellularization remains an important component in the processing of ECM-based scaffolds.
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Inadequate decellularization retains high amounts of DAMPs or endotoxin, and excessive crosslinking biases macrophages toward pro-inflammatory phenotypes that drive fibrosis and poor remodeling.
“Mechanistically, inadequate decellularization retains high amounts of damage-associated molecular patterns (DAMPs) or endotoxin, and excessive crosslinking biases macrophages toward pro-inflammatory phenotypes that drive fibrosis and poor remodeling [73,74].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [73]
Insufficient DNA removal correlates with increased inflammatory infiltration and impaired remodeling.
“Some studies have shown that insufficient DNA removal correlates with increased inflammatory infiltration and impaired remodeling [73].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [73]
Not all decellularization protocols are equally effective at removing cells or other immunogenic species, which can cause varying host immune responses and failure of implants in clinical trials.
“A related difficulty is that not all decellularization protocols are equally effective at removing cells or other immunogenic species, which can cause varying host immune responses and failure of implants in clinical trials122.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [122]
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“Mechanistically, inadequate decellularization retains high amounts of damage-associated molecular patterns (DAMPs) or endotoxin, and excessive crosslinking biases macrophages toward pro-inflammatory phenotypes that drive fibrosis and poor remodeling [73,74].”
- Authors
- Keane, T. J., Londono, R., Turner, N. J., & Badylak, S. F.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Badylak, Stephen F.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 33
- Issue
- 6
- Pages
- 1771-1781
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W1984133400
- Cited by
- 613
- References
- 71
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 38 · 2023: 41 · 2022: 41 · 2021: 59 · 2020: 41 · 2019: 49 · 2018: 47 · 2017: 60 · 2016: 45 · 2015: 40 · 2014: 46 · 2013: 47 · 2012: 17
- FWCI
- 35.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 AR054940)
- 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
- decellularization, biological scaffolds, extracellular matrix, small intestinal submucosa, host response, macrophage polarization, M1/M2 macrophages, tissue remodeling, DNA fragmentation
- MeSH terms
- Animals, Biocompatible Materials, DNA, Extracellular Matrix, Immune System, Intestine, Small, Macrophages, Materials Testing, Models, Biological, Peracetic Acid, Phenotype, Swine, Time Factors, Wound Healing, Tissue Engineering, Mice, Tissue Scaffolds
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