title: Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.
abstract: Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair.
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Sadtler
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Estrellas
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Allen
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Wolf
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hongni
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ada J
authors.initials: AJ
authors.lastname: Tam
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Chirag H
authors.initials: CH
authors.lastname: Patel
authors.affiliation: Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Luber
authors.affiliation: Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MD 21205, USA, and Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Powell
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Franck
authors.initials: F
authors.lastname: Housseau
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.affiliation: Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21287, USA. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001672:Biocompatible Materials; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006706:Homeostasis / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000293:injuries* / Q000502:physiology*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000276:immunology*
chemical_list: D001672:Biocompatible Materials; D002352:Carrier Proteins; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C525637:rictor protein, mouse; D015847:Interleukin-4; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases