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Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival.
Uehara, Mayuko; Li, Xiaofei; Sheikhi, Amir; Zandi, Nooshin; Walker, Brian; Saleh, Bahram; Banouni, Naima; Jiang, Liwei; Ordikhani, Farideh; Dai, Li; Yonar, Merve; Vohra, Ishaan; Kasinath, Vivek; Orgill, Dennis P; Khademhosseini, Ali; Annabi, Nasim; Abdi, Reza.
Affiliation
  • Uehara M; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Li X; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Sheikhi A; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
  • Zandi N; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Walker B; Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
  • Saleh B; Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute (CNSI), University of California, Los Angeles, CA, 90095, USA.
  • Banouni N; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
  • Jiang L; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Ordikhani F; Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran, Iran.
  • Dai L; Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
  • Yonar M; Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA.
  • Vohra I; Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA.
  • Kasinath V; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Orgill DP; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Khademhosseini A; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Annabi N; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Abdi R; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Sci Rep ; 9(1): 6535, 2019 04 25.
Article in En | MEDLINE | ID: mdl-31024011
ABSTRACT
A primary goal in the management of burn wounds is early wound closure. The use of skin allografts represents a lifesaving strategy for severe burn patients, but their ultimate rejection limits their potential efficacy and utility. IL-6 is a major pleiotropic cytokine which critically links innate and adaptive immune responses. Here, we devised anti-IL-6 receptor eluting gelatin methacryloyl (GelMA) biomaterials (GelMA/anti-IL-6), which were implanted at the interface between the wound beds and skin allografts. Our visible light crosslinked GelMA/anti-IL-6 immunomodulatory biomaterial (IMB) demonstrated a stable kinetic release profile of anti-IL-6. In addition, the incorporation of anti-IL-6 within the GelMA hydrogel had no effect on the mechanical properties of the hydrogels. Using a highly stringent skin transplant model, the GelMA/anti-IL-6 IMB almost doubled the survival of skin allografts. The use of GelMA/anti-IL-6 IMB was far superior to systemic anti-IL-6 receptor treatment in prolonging skin allograft survival. As compared to the untreated control group, skin from the GelMA/anti-IL-6 IMB group contained significantly fewer alloreactive T cells and macrophages. Interestingly, the environmental milieu of the draining lymph nodes (DLNs) of the mice implanted with the GelMA/anti-IL-6 IMB was also considerably less pro-inflammatory. The percentage of CD4+ IFNγ+ cells was much lower in the DLNs of the GelMA/anti-IL-6 IMB group in comparison to the GelMA group. These data highlight the importance of localized immune delivery in prolonging skin allograft survival and its potential utility in treating patients with severe burns.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biocompatible Materials / Interleukin-6 / Skin Transplantation / Allografts / Graft Survival / Immunologic Factors Type of study: Prognostic_studies Limits: Animals Language: En Journal: Sci Rep Year: 2019 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biocompatible Materials / Interleukin-6 / Skin Transplantation / Allografts / Graft Survival / Immunologic Factors Type of study: Prognostic_studies Limits: Animals Language: En Journal: Sci Rep Year: 2019 Document type: Article Affiliation country: United States