Lipid Deposition Profiles Influence Foreign Body Responses

Author:

Schreib Christian C.1,Jarvis Maria I.12,Terlier Tanguy3,Goell Jacob1,Mukherjee Sudip14,Doerfert Michael D.1,Wilson Taylor Anne5,Beauregard Michael1,Martins Kevin N.5,Lee Jared6,Sanchez Solis Leonardo D.1,Vazquez Esperanza7,Oberli Matthias A.89,Hanak Brian W.5,Diehl Michael1,Hilton Isaac110,Veiseh Omid110ORCID

Affiliation:

1. Department of Bioengineering Rice University 6500 Main Street Houston TX 77030 USA

2. Lonza Inc.  14905 Kirby Drive Houston TX 77047 USA

3. SIMS laboratory Shared Equipment Authority Rice University 6500 Main Street Houston TX 77030 USA

4. School of Biomedial Engineering IIT (BHU) Varanasi Uttar Pradesh 221005 India

5. Department of Neurosurgery Loma Linda University Health 11234 Anderson St Loma Linda CA 92354 USA

6. Department of Chemistry Rice University 6100 Main St Houston TX 77005 USA

7. Department of Biomedical Engineering University of Houston 3517 Cullen Blvd Houston TX 77204 USA

8. Sigilon Therapeutics 200 Dexter Avenue Watertown MA 02472 USA

9. Xibus systems Inc.  200 Dexter Avenue Watertown MA 02472 USA

10. Program of Synthetic Systems and Physical Biology Rice University 6500 Main Street Houston TX 77030 USA

Abstract

AbstractFibrosis remains a significant cause of failure in implanted biomedical devices and early absorption of proteins on implant surfaces has been shown to be a key instigating factor. However, lipids can also regulate immune activity and their presence may also contribute to biomaterial‐induced foreign body responses (FBR) and fibrosis. Here it is demonstrated that the surface presentation of lipids on implant affects FBR by influencing reactions of immune cells to materials as well as their resultant inflammatory/suppressive polarization. Time‐of‐flight secondary ion mass spectroscopy (ToF‐SIMS) is employed to characterize lipid deposition on implants that are surface‐modified chemically with immunomodulatory small molecules. Multiple immunosuppressive phospholipids (phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin) are all found to deposit preferentially on implants with anti‐FBR surface modifications in mice. Significantly, a set of 11 fatty acids is enriched on unmodified implanted devices that failed in both mice and humans, highlighting relevance across species. Phospholipid deposition is also found to upregulate the transcription of anti‐inflammatory genes in murine macrophages, while fatty acid deposition stimulated the expression of pro‐inflammatory genes. These results provide further insights into how to improve the design of biomaterials and medical devices to mitigate biomaterial material‐induced FBR and fibrosis.

Funder

Defense Advanced Research Projects Agency

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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