Protease-degradable microgels for protein delivery for vascularization

Biomaterials. 2017 Jan:113:170-175. doi: 10.1016/j.biomaterials.2016.10.044. Epub 2016 Oct 28.

Abstract

Degradable hydrogels to deliver bioactive proteins represent an emerging platform for promoting tissue repair and vascularization in various applications. However, implanting these biomaterials requires invasive surgery, which is associated with complications such as inflammation, scarring, and infection. To address these shortcomings, we applied microfluidics-based polymerization to engineer injectable poly(ethylene glycol) microgels of defined size and crosslinked with a protease degradable peptide to allow for triggered release of proteins. The release rate of proteins covalently tethered within the microgel network was tuned by modifying the ratio of degradable to non-degradable crosslinkers, and the released proteins retained full bioactivity. Microgels injected into the dorsum of mice were maintained in the subcutaneous space and degraded within 2 weeks in response to local proteases. Furthermore, controlled release of VEGF from degradable microgels promoted increased vascularization compared to empty microgels or bolus injection of VEGF. Collectively, this study motivates the use of microgels as a viable method for controlled protein delivery in regenerative medicine applications.

Keywords: Biomaterials; Hydrogels; Microfluidics; Protein delivery; VEGF.

MeSH terms

  • Angiogenesis Inducing Agents / administration & dosage*
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / metabolism*
  • Hydrogels / chemistry
  • Hydrogels / metabolism*
  • Lab-On-A-Chip Devices
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects*
  • Peptide Hydrolases / metabolism*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / metabolism*
  • Polymerization
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Angiogenesis Inducing Agents
  • Delayed-Action Preparations
  • Hydrogels
  • Vascular Endothelial Growth Factor A
  • Polyethylene Glycols
  • Peptide Hydrolases