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Author Notes:

Corresponding Author: Edward Botchwey, Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Ga 30332, Email: edward.botchwey@bme.gatech.edu, Phone: (404) 385-5058, Fax: (404) 894-4243

We thank the core facilities staff of the Parker H. Petit Institute for Bioengineering and Bioscience for technical expertise and assistance.

In addition we thank the Emory University Integrated Cellular Imaging Microscopy Core for their expertise and assistance in image analysis.

Subject:

Research Funding:

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:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Vascularization
  • Immunomodulation
  • Angiogenesis
  • Arteriogenesis
  • SDF-1
  • Hydrogel
  • BONE MORPHOGENETIC PROTEIN-2
  • SPHINGOSINE 1-PHOSPHATE
  • MYOCARDIAL-INFARCTION
  • PROGENITOR CELLS
  • SPINAL-CORD
  • MACROPHAGES
  • HEPARIN
  • ARTERIOGENESIS
  • REGENERATION
  • TISSUE

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

Tools:

Journal Title:

Biomaterials

Volume:

Volume 77

Publisher:

, Pages 280-290

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2015 Elsevier Ltd.

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