Dual delivery of IL-10 and AT-RvD1 from PEG hydrogels polarize immune cells towards pro-regenerative phenotypes
| Autor: | Edward A. Botchwey, Joshua I. Palacios, Andrés J. García, Mary Caitlin P. Sok, Hong Seo Lim, José R. García, Claire McClain, Peng Qiu, Molly E. Ogle, Claire E. Olingy, Nusaiba Baker, Thomas C. Turner, Krithik Srithar, L. A. Hymel |
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| Rok vydání: | 2020 |
| Předmět: |
Biophysics
Bioengineering Inflammation Context (language use) Biocompatible Materials 02 engineering and technology Biomaterials 03 medical and health sciences Immune system medicine Humans 030304 developmental biology 0303 health sciences Aspirin business.industry Regeneration (biology) Peripheral tolerance Hydrogels 021001 nanoscience & nanotechnology Cell biology Interleukin-10 Interleukin 10 Phenotype Mechanics of Materials Self-healing hydrogels Ceramics and Composites medicine.symptom 0210 nano-technology Wound healing business |
| Zdroj: | Biomaterials. 268 |
| ISSN: | 1878-5905 |
| Popis: | Inflammation after traumatic injury or surgical intervention is both a protective tissue response leading to regeneration and a potential cause of wound complications. One potentially successful strategy to harness to pro-regenerative roles of host inflammation is the localized delivery of bioactive materials to induce immune suppressive cellular responses by cells responding to injury. In this study, we designed a fully synthetic poly (ethylene) glycol (PEG)-based hydrogel to release the specialized pro-resolving lipid mediator aspirin-triggered resolvin-D1 (AT-RvD1) and recombinant human interleukin 10 (IL-10). We utilized a unique side-by-side internally controlled implant design wherein bioactive hydrogels were implanted adjacent to control hydrogels devoid of immune modulatory factors in the dorsal skinfold window chamber. We also explored single-immune cell data with unsupervised approaches such as SPADE. First, we show that RGD-presenting hydrogel delivery results in enhanced immune cell recruitment to the site of injury. We then use intra-vital imaging to assess cellular recruitment and microvascular remodeling to show an increase in the caliber and density of local microvessels. Finally, we show that the recruitment and re-education of mononuclear phagocytes by combined delivery IL-10 and AT-RvD1 localizes immune suppressive subsets to the hydrogel, including CD206+ macrophages (M2a/c) and IL-10 expressing dendritic cells in the context of chronic inflammation following surgical tissue disruption. These data demonstrate the potential of combined delivery on the recruitment of regenerative cell subsets involved in wound healing complications. |
| Databáze: | OpenAIRE |
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