Modulating the Foreign Body Response of Implants for Diabetes Treatment

Overview

Journal Adv Drug Deliv Rev

Specialty Pharmacology

Date 2021 Jan 23

PMID 33484736

Citations 24

Authors

Bhushan N Kharbikar

Gauree S Chendke

Tejal A Desai

Affiliations

Soon will be listed here.

Abstract

Diabetes Mellitus is a group of diseases characterized by high blood glucose levels due to patients' inability to produce sufficient insulin. Current interventions often require implants that can detect and correct high blood glucose levels with minimal patient intervention. However, these implantable technologies have not reached their full potential in vivo due to the foreign body response and subsequent development of fibrosis. Therefore, for long-term function of implants, modulating the initial immune response is crucial in preventing the activation and progression of the immune cascade. This review discusses the different molecular mechanisms and cellular interactions involved in the activation and progression of foreign body response (FBR) and fibrosis, specifically for implants used in diabetes. We also highlight the various strategies and techniques that have been used for immunomodulation and prevention of fibrosis. We investigate how these general strategies have been applied to implants used for the treatment of diabetes, offering insights on how these devices can be further modified to circumvent FBR and fibrosis.

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References

Orive G, Emerich D, Khademhosseini A, Matsumoto S, Hernandez R, Pedraz J . Engineering a Clinically Translatable Bioartificial Pancreas to Treat Type I Diabetes. Trends Biotechnol. 2018; 36(4):445-456. DOI: 10.1016/j.tibtech.2018.01.007. View

Yin C, Chia S, Quek C, Yu H, Zhuo R, Leong K . Microcapsules with improved mechanical stability for hepatocyte culture. Biomaterials. 2003; 24(10):1771-80. DOI: 10.1016/s0142-9612(02)00580-x. View

SoRelle J, Itoh T, Peng H, Kanak M, Sugimoto K, Matsumoto S . Withaferin A inhibits pro-inflammatory cytokine-induced damage to islets in culture and following transplantation. Diabetologia. 2013; 56(4):814-24. DOI: 10.1007/s00125-012-2813-9. View

Iqbal Z, Moses W, Kim S, Kim E, Fissell W, Roy S . Sterilization effects on ultrathin film polymer coatings for silicon-based implantable medical devices. J Biomed Mater Res B Appl Biomater. 2017; 106(6):2327-2336. PMC: 5936672. DOI: 10.1002/jbm.b.34039. View

Frid A, Kreugel G, Grassi G, Halimi S, Hicks D, Hirsch L . New Insulin Delivery Recommendations. Mayo Clin Proc. 2016; 91(9):1231-55. DOI: 10.1016/j.mayocp.2016.06.010. View

Dong Y, Wang W, Veiseh O, Appel E, Xue K, Webber M . Injectable and Glucose-Responsive Hydrogels Based on Boronic Acid-Glucose Complexation. Langmuir. 2016; 32(34):8743-7. PMC: 5242094. DOI: 10.1021/acs.langmuir.5b04755. View

QUINN C, Connor R, Heller A . Biocompatible, glucose-permeable hydrogel for in situ coating of implantable biosensors. Biomaterials. 1998; 18(24):1665-70. DOI: 10.1016/s0142-9612(97)00125-7. View

Dang T, Thai A, Cohen J, Slosberg J, Siniakowicz K, Doloff J . Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug. Biomaterials. 2013; 34(23):5792-801. PMC: 3901568. DOI: 10.1016/j.biomaterials.2013.04.016. View

Marigliano M, Bertera S, Grupillo M, Trucco M, Bottino R . Pig-to-nonhuman primates pancreatic islet xenotransplantation: an overview. Curr Diab Rep. 2011; 11(5):402-12. PMC: 3167044. DOI: 10.1007/s11892-011-0213-z. View

10.

Villa C, Manzoli V, Abreu M, Verheyen C, Seskin M, Najjar M . Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice. Transplantation. 2016; 101(5):1025-1035. PMC: 5642344. DOI: 10.1097/TP.0000000000001454. View

11.

Welch N, Winkler D, Thissen H . Antifibrotic strategies for medical devices. Adv Drug Deliv Rev. 2020; 167:109-120. DOI: 10.1016/j.addr.2020.06.008. View

12.

Giraldo J, Molano R, Rengifo H, Fotino C, Gattas-Asfura K, Pileggi A . The impact of cell surface PEGylation and short-course immunotherapy on islet graft survival in an allogeneic murine model. Acta Biomater. 2016; 49:272-283. PMC: 5253093. DOI: 10.1016/j.actbio.2016.11.060. View

13.

Thabit H, Hovorka R . Coming of age: the artificial pancreas for type 1 diabetes. Diabetologia. 2016; 59(9):1795-805. PMC: 4969330. DOI: 10.1007/s00125-016-4022-4. View

14.

Langer R . Islet transplantation: lessons learned since the Edmonton breakthrough. Transplant Proc. 2010; 42(5):1421-4. DOI: 10.1016/j.transproceed.2010.04.021. View

15.

Lecomte A, Descamps E, Bergaud C . A review on mechanical considerations for chronically-implanted neural probes. J Neural Eng. 2017; 15(3):031001. DOI: 10.1088/1741-2552/aa8b4f. View

16.

Bridges A, Garcia A . Anti-inflammatory polymeric coatings for implantable biomaterials and devices. J Diabetes Sci Technol. 2009; 2(6):984-94. PMC: 2769825. DOI: 10.1177/193229680800200628. View

17.

Jokinen V, Kankuri E, Hoshian S, Franssila S, Ras R . Superhydrophobic Blood-Repellent Surfaces. Adv Mater. 2018; 30(24):e1705104. DOI: 10.1002/adma.201705104. View

18.

Stabler C, Li Y, Stewart J, Keselowsky B . Engineering immunomodulatory biomaterials for type 1 diabetes. Nat Rev Mater. 2020; 4(6):429-450. PMC: 7332200. DOI: 10.1038/s41578-019-0112-5. View

19.

Klopfleisch R . Macrophage reaction against biomaterials in the mouse model - Phenotypes, functions and markers. Acta Biomater. 2016; 43:3-13. DOI: 10.1016/j.actbio.2016.07.003. View

20.

Weaver J, Headen D, Hunckler M, Coronel M, Stabler C, Garcia A . Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation. Biomaterials. 2018; 172:54-65. PMC: 5967258. DOI: 10.1016/j.biomaterials.2018.04.047. View