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Cited by 16Tissue Engineering and Regenerative MedicineXenotransplantation and immune responseCollagen: Extraction and Characterization

Lack of immunogenicity of xenogeneic DNA from porcine biomaterials

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Record Ritchie, Rae D., Salmon, Sharon L., Hiles, Michael C., Metzger, Dennis W.·2022·Surgery Open Science
DOI 10.1016/j.sopen.2022.07.005PMC PMC9418979
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Abstract

Background: Clinically useful biomaterials are derived from xenogeneic extracellular matrices, but extensive processes often used to remove all residual DNA are detrimental to their proper biological function. We hypothesized that deliberate and repeated injection of DNA extracted from clinically implantable, xenogeneic extracellular matrices might elicit an immune response in a well-established murine model that could ultimately lead to altered extracellular matrix remodeling. Methods: ; (2) DNA from unprocessed porcine extracellular matrices combined with interleukin-12 and methylated bovine serum albumin and emulsified in incomplete Freund's adjuvant; and (3) buffered saline. Immunizations occurred every 2 weeks for a total of 3 injections. Local cytokines and systemic anti-DNA antibodies were quantified 3 and 7 days after final injection. Results: The DNA extracted from unprocessed, aseptic, or sterilized porcine extracellular matrices failed to elicit a rejection response, and only with significant, proinflammatory adjuvant activation could such a response be seen. Without the adjuvants, biomaterial-derived DNA resulted in a mild accommodation cytokine response locally and no systemic anti-DNA antibody expression even at doses approximately 100-fold larger than would be clinically likely via extracellular matrix implantation. Conclusion: The immunological safety of porcine extracellular matrix biomaterials appears not to be related to DNA residues present. Such biomaterials need not be extensively processed, likely leading to detrimental changes in their bioactivity, solely in an effort to remove the mammalian DNA.

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  • DNA alone does not elicit significant immune responses unless presented alongside adjuvants or in pro-inflammatory environments.

    “Others suggest that DNA alone does not elicit significant immune responses unless presented alongside adjuvants or in pro-inflammatory environments [130].”

    From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [130]

    The Introduction and Results report that porcine biomaterial-derived DNA did not induce anti-DNA antibodies without strong adjuvants, and that a rejection response appeared only with proinflammatory adjuvant activation. The claim is broader than those findings: the study did not test pro-inflammatory environments generally, and DNA without adjuvants did produce a mild local cytokine response (Abstract, Results; Results, Cytokine Induction by SIS-Derived pDNA). (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Residual DNA within dECM cannot elicit rejection in the absence of immunogenic adjuvants.

    “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 [57]

    The Introduction and Discussion report that porcine SIS-derived DNA did not elicit an anti-DNA antibody response in mice without strong adjuvants. But the study tested extracted DNA from one ECM source, not residual DNA within all dECM implants; the Discussion explicitly says its results cannot be extrapolated to all ECM-based products. No page numbers are supplied in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Xenogeneic DNA present in porcine biologic scaffolds is not linked to an inflammatory immune response, but to other factors such as endotoxins.

    “In fact, recent studies have shown that xenogeneic DNA present in porcine biologic scaffolds is not linked to an inflammatory immune response [130], but to other factors such as endotoxins [131].”

    From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [130]

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Authors
Record Ritchie, R. D., Salmon, S. L., Hiles, M. C., & Metzger, D. W.
Affiliations
  • Albany Medical College (US)
  • Cook Biotech (United States) (US)
ORCID
Metzger, Dennis W.
Venue
Surgery Open Science
Publisher
Elsevier BV
Published
2022-10
Volume
10
Pages
83-90
ISSN
2589-8450 (ISSN-L)
DOI
10.1016/j.sopen.2022.07.005
PMC
PMC9418979
OpenAlex
W4286449180
Cited by
16
References
46
Citations by year
2026: 1 · 2025: 8 · 2024: 4 · 2023: 3
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Surgery Open Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
Keywords
xenotransplantation, anti-DNA antibodies, IL-12, Freund's adjuvant, biomaterial processing, extracellular matrix remodeling, immunological safety, cytokine response

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