Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival

Mayuko Uehara, Xiaofei Li, Amir Sheikhi, Nooshin Zandi, Brian Walker, Bahram Saleh, Naima Banouni, Liwei Jiang, Farideh Ordikhani, Li Dai, Merve Yonar, Ishaan Vohra, Vivek Kasinath, Dennis P. Orgill, Ali Khademhosseini, Nasim Annabi, Reza Abdi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number6535
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Biocompatible Materials
Gelatin
Allografts
Interleukin-6
Skin
Wounds and Injuries
Lymph Nodes
Hydrogels
Hydrogel
Adaptive Immunity
Burns
Innate Immunity
Macrophages
Cytokines
T-Lymphocytes
Transplants
Light
Control Groups

All Science Journal Classification (ASJC) codes

  • General

Cite this

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. / Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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title = "Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival",
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.",
author = "Mayuko Uehara and Xiaofei Li and Amir Sheikhi and Nooshin Zandi and Brian Walker and Bahram Saleh and Naima Banouni and Liwei Jiang and Farideh Ordikhani and Li Dai and Merve Yonar and Ishaan Vohra and Vivek Kasinath and Orgill, {Dennis P.} and Ali Khademhosseini and Nasim Annabi and Reza Abdi",
year = "2019",
month = "12",
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Uehara, M, Li, X, Sheikhi, A, Zandi, N, Walker, B, Saleh, B, Banouni, N, Jiang, L, Ordikhani, F, Dai, L, Yonar, M, Vohra, I, Kasinath, V, Orgill, DP, Khademhosseini, A, Annabi, N & Abdi, R 2019, 'Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival', Scientific reports, vol. 9, no. 1, 6535. https://doi.org/10.1038/s41598-019-42349-w

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.

In: Scientific reports, Vol. 9, No. 1, 6535, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival

AU - Uehara, Mayuko

AU - Li, Xiaofei

AU - Sheikhi, Amir

AU - Zandi, Nooshin

AU - Walker, Brian

AU - Saleh, Bahram

AU - Banouni, Naima

AU - Jiang, Liwei

AU - Ordikhani, Farideh

AU - Dai, Li

AU - Yonar, Merve

AU - Vohra, Ishaan

AU - Kasinath, Vivek

AU - Orgill, Dennis P.

AU - Khademhosseini, Ali

AU - Annabi, Nasim

AU - Abdi, Reza

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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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