title: Spatially localized recruitment of anti-inflammatory monocytes by SDF-1α-releasing hydrogels enhances microvascular network remodeling.
abstract: Tissue repair processes are characterized by the biphasic recruitment of distinct subpopulations of blood monocytes, including classical ("inflammatory") monocytes (IMs, Ly6C(hi)Gr1(+)CX3CR1(lo)) and non-classical anti-inflammatory monocytes (AMs, Ly6C(lo)Gr1(-)CX3CR1(hi)). Drug-eluting biomaterial implants can be used to tune the endogenous repair process by the preferential recruitment of pro-regenerative cells. To enhance recruitment of AMs during inflammatory injury, a novel N-desulfated heparin-containing poly(ethylene glycol) diacrylate (PEG-DA) hydrogel was engineered to deliver exogenous stromal derived factor-1α (SDF-1α), utilizing the natural capacity of heparin to sequester and release growth factors. SDF-1α released from the hydrogels maintained its bioactivity and stimulated chemotaxis of bone marrow cells in vitro. Intravital microscopy and flow cytometry demonstrated that SDF-1α hydrogels implanted in a murine dorsal skinfold window chamber promoted spatially-localized recruitment of AMs relative to unloaded internal control hydrogels. SDF-1α delivery stimulated arteriolar remodeling that was correlated with AM enrichment in the injury niche. SDF-1α, but not unloaded control hydrogels, supported sustained arteriogenesis and microvascular network growth through 7 days. The recruitment of AMs correlated with parameters of vascular remodeling suggesting that tuning the innate immune response by biomaterial SDF-1α release is a promising strategy for promoting vascular remodeling in a spatially controlled manner.
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Krieger
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Ogle
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: J
authors.initials: J
authors.lastname: McFaline-Figueroa
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Segar
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Temenoff
authors.affiliation: W.H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: edward.botchwey@bme.gatech.edu.
authors.forename: E A
authors.initials: EA
authors.lastname: Botchwey
mesh_terms: D000818:Animals; D001160:Arterioles / Q000254:growth & development / Q000648:ultrastructure; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006493:Heparin; D020100:Hydrogels; D007249:Inflammation; D000069416:Intravital Microscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055806:Microvessels / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012884:Skin Window Technique; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D054377:Chemokine CXCL12; D020100:Hydrogels; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; C437167:poly(ethylene glycol)diacrylate; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D006493:Heparin
keywords: Angiogenesis; Arteriogenesis; Hydrogel; Immunomodulation; SDF-1; Vascularization