Protease-degradable microgels for protein delivery for vascularization.
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.
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Greg A
GA
Foster
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
Devon M
DM
Headen
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; School of Engineering, Division of Biomedical Engineering, University of Glasgow, Glasgow, Scotland, UK.
Cristina
C
González-García
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; School of Engineering, Division of Biomedical Engineering, University of Glasgow, Glasgow, Scotland, UK.
Manuel
M
Salmerón-Sánchez
Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Haval
H
Shirwan
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: andres.garcia@me.gatech.edu.
Andrés J
AJ
García
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism*; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism*; D056656:Lab-On-A-Chip Devices; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D058105:Polymerization; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D010447:Peptide Hydrolases
Biomaterials; Hydrogels; Microfluidics; Protein delivery; VEGF