Spatially localized recruitment of anti-inflammatory monocytes by SDF-1 alpha-releasing hydrogels enhances microvascular network remodeling

• Type of Material: Article
• Authors: JR Krieger, Georgia Institute of Technology; ME Ogle, Georgia Institute of Technology; J McFaline-Figueroa, Georgia Institute of Technology; CE Segar, Georgia Institute of Technology; Johnna Sue Temenoff, Emory University; Edward Botchwey, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2015.10.045
• Title of Journal or Parent Work: Biomaterials
• ISSN: 0142-9612
• Volume: 77
• Start Page: 280
• End Page: 290
• Grant/Funding Information: Sources of support for this study include the National Institutes of Health grants K01AR052352-01A1, R01AR056445-01A2, and R01DE019935-01 to Dr. Botchwey and Petit Faculty Fellowship funds for Dr. Temenoff.
• Keywords: Angiogenesis; Materials Science; MYOCARDIAL-INFARCTION; HEPARIN; Arteriogenesis; SDF-1; REGENERATION; MACROPHAGES; Vascularization; ARTERIOGENESIS; Materials Science, Biomaterials; BONE MORPHOGENETIC PROTEIN-2; PROGENITOR CELLS; Immunomodulation; Hydrogel; Engineering; TISSUE; Engineering, Biomedical; SPHINGOSINE 1-PHOSPHATE; Technology; Science & Technology; SPINAL-CORD
• Research Categories: Engineering, Biomedical

Abstract

Tissue repair processes are characterized by the biphasic recruitment of distinct subpopulations of blood monocytes, including classical ("inflammatory") monocytes (IMs, Ly6ChiGr1+CX3CR1lo) and non-classical anti-inflammatory monocytes (AMs, Ly6CloGr1-CX3CR1hi). 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.