title: Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted islets.
abstract: Biomaterial scaffolds are central to many regenerative strategies as they create a space for infiltration of host tissue and provide a platform to deliver growth factors and progenitor cells. However, biomaterial implantation results in an unavoidable inflammatory response, which can impair tissue regeneration and promote loss or dysfunction of transplanted cells. We investigated localized TGF-β1 delivery to modulate this immunological environment around scaffolds and transplanted cells. TGF-β1 was delivered from layered scaffolds, with protein entrapped within an inner layer and outer layers designed for cell seeding and host tissue integration. Scaffolds were implanted into the epididymal fat pad, a site frequently used for cell transplantation. Expression of cytokines TNF-α, IL-12, and MCP-1 were decreased by at least 40% for scaffolds releasing TGF-β1 relative to control scaffolds. This decrease in inflammatory cytokine production corresponded to a 60% decrease in leukocyte infiltration. Transplantation of islets into diabetic mice on TGF-β1 scaffolds significantly improved the ability of syngeneic islets to control blood glucose levels within the first week of transplant and delayed rejection of allogeneic islets. Together, these studies emphasize the ability of localized TGF-β1 delivery to modulate the immune response to biomaterial implants and enhance cell function in cell-based therapies.
authors.affiliation: Interdisciplinary Biological Sciences Program, Northwestern University, Evanston, IL 60208, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jeffrey M H
authors.initials: JMH
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Division of Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Kelan A
authors.initials: KA
authors.lastname: Hlavaty
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Christine F
authors.initials: CF
authors.lastname: Ricci
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Leonard
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ldshea@umich.edu.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
authors.affiliation: Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA; Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, USA. Electronic address: gowerrm@mailbox.sc.edu.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Gower
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D016503:Drug Delivery Systems / Q000379:methods; D056747:Immunomodulation / Q000187:drug effects; D018664:Interleukin-12 / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016062:Porosity; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12
keywords: Immunoengineering; Immunomodulation; Leukocyte; Scaffold; Transplant