Osteopontin attenuates the foreign-body response to silicone implants

Michelle F Griffin^#¹, Jennifer B Parker^#^{1

2}, Ruth Tevlin¹, Norah E Liang¹, Caleb Valencia^{1

2}, Annah Morgan¹, Maxwell Kuhnert¹, Mauricio Downer Jr¹, Emily L Meany³, Jason L Guo¹, Dominic Henn¹, Renato S Navarro⁴, Kerry Shefren¹, Dung Nguyen¹, Geoffrey C Gurtner¹, Sarah C Heilshorn⁴, Charles K F Chan^{1

2}, Michael Januszyk¹, Eric A Appel⁴, Arash Momeni⁵, Derrick C Wan⁶, Michael T Longaker^{7

8}

Affiliations

¹ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
² Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁴ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
⁵ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. amomeni@stanford.edu.
⁶ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. dwan@stanford.edu.
⁷ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. longaker@stanford.edu.
⁸ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. longaker@stanford.edu.

^# Contributed equally.

PMID: 40128393
DOI: 10.1038/s41551-025-01361-4

Osteopontin attenuates the foreign-body response to silicone implants

Michelle F Griffin et al. Nat Biomed Eng. 2025 Aug.

. 2025 Aug;9(8):1254-1275.

doi: 10.1038/s41551-025-01361-4. Epub 2025 Mar 24.

Authors

Affiliations

¹ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
² Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁴ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
⁵ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. amomeni@stanford.edu.
⁶ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. dwan@stanford.edu.
⁷ Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. longaker@stanford.edu.
⁸ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. longaker@stanford.edu.

^# Contributed equally.

PMID: 40128393
DOI: 10.1038/s41551-025-01361-4

Abstract

The inflammatory process resulting in the fibrotic encapsulation of implants has been well studied. However, how acellular dermal matrix (ADM) used in breast reconstruction elicits an attenuated foreign-body response (FBR) remains unclear. Here, by leveraging single-cell RNA-sequencing and proteomic data from pairs of fibrotically encapsulated specimens (bare silicone and silicone wrapped with ADM) collected from individuals undergoing breast reconstruction, we show that high levels of the extracellular-matrix protein osteopontin are associated with the use of ADM as a silicone wrapping. In mice with osteopontin knocked out, FBR attenuation by ADM-coated implants was abrogated. In wild-type mice, the sustained release of recombinant osteopontin from a hydrogel placed adjacent to a silicone implant attenuated the FBR in the absence of ADM. Our findings suggest strategies for the further minimization of the FBR.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Major, M. R., Wong, V. W., Nelson, E. R., Longaker, M. T. & Gurtner, G. C. The foreign body response: at the interface of surgery and bioengineering. Plast. Reconstr. Surg. 135, 1489–1498 (2015). - PubMed
1. Parker, J. B., Griffin, M. F., Spielman, A. F., Wan, D. C. & Longaker, M. T. Exploring the overlooked roles and mechanisms of fibroblasts in the foreign body response. Adv. Wound Care 12, 85–96 (2023).
1. Anderson, J. M., Rodriguez, A. & Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008). - PubMed
1. Gibon, E. et al. The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction. J. Biomed. Mater. Res. B 105, 1685–1691 (2017).
1. Carnicer-Lombarte, A., Chen, S. T., Malliaras, G. G. & Barone, D. G. Foreign body reaction to implanted biomaterials and its impact in nerve neuroprosthetics. Front. Bioeng. Biotechnol. 9, 622524 (2021). - PubMed - PMC

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Osteopontin attenuates the foreign-body response to silicone implants

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Osteopontin attenuates the foreign-body response to silicone implants

Authors

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Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

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Medical

Research Materials