Aptamer-Functionalized Fibrin Hydrogel Improves Vascular Endothelial Growth Factor Release Kinetics and Enhances Angiogenesis and Osteogenesis in Critically Sized Cranial Defects

Otto Juhl, Nan Zhao, Anna Blessing Merife, David Cohen, Michael Friedman, Yue Zhang, Zvi Schwartz, Yong Wang, Henry Donahue

Research output: Contribution to journalArticle

Abstract

An aging population, decreased activity levels and increased combat injuries, have led to an increase in critical sized bone defects. As more defects are treated using allografts, which is the current standard of care, the deficiencies of allografts are becoming more evident. Allografts lack the angiogenic potential to induce sufficient vasculogenesis to counteract the hypoxic environment associated with critical sized bone defects. In this study, aptamer-functionalized fibrin hydrogels (AFH), engineered to release vascular endothelial growth factor (VEGF), were evaluated for their material properties, growth factor release kinetics, and angiogenic and osteogenic potential in vivo. Aptamer functionalization to native fibrin did not result in significant changes in biocompatibility or hydrogel gelation. However, aptamer functionalization of fibrin did improve the release kinetics of VEGF from AFH and, when compared to FH, reduced the diffusivity and extended the release of VEGF several days longer. VEGF released from AFH, in vivo, increased vascularization to a greater degree, relative to VEGF released from FH, in a murine critical-sized cranial defect. Defects treated with AFH loaded with VEGF, relative to nonhydrogel loaded controls, showed a nominal increase in osteogenesis. Together, these data suggest that AFH more efficiently incorporates and retains VEGF in vitro and in vivo, which then enhances angiogenesis and osteogenesis to a greater extent in vivo than FH.

Original languageEnglish (US)
JournalACS Biomaterials Science and Engineering
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • biomaterial
  • bone regeneration
  • drug delivery
  • growth factor
  • regenerative medicine

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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