Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration.
Bioactive glasses are potentially useful as bone defect fillers, and vascular endothelial growth factor (VEGF) has demonstrated benefit in bone regeneration as well. We hypothesized that the specific combination of prolonged localized VEGF presentation from a matrix coated with a bioactive glass may enhance bone regeneration. To test this hypothesis, the capacity of VEGF-releasing polymeric scaffolds with a bioactive glass coating was examined in vitro and in vivo using a rat critical-sized defect model. In the presence of a bioactive glass coating, we did not detect pronounced differences in the differentiation of human mesenchymal stem cells in vitro. However, we observed significantly enhanced mitogenic stimulation of endothelial cells in the presence of the bioactive glass coating, with an additive effect with VEGF release. This trend was maintained in vivo, where coated VEGF-releasing scaffolds demonstrated significant improvements in blood vessel density at 2 weeks versus coated control scaffolds. At 12 weeks, bone mineral density was significantly increased in coated VEGF-releasing scaffolds versus coated controls, while only a slight increase in bone volume fraction was observed. The results of this study suggest that a bioactive glass coating on a polymeric substrate participates in bone healing through indirect processes which enhance angiogenesis and bone maturation and not directly on osteoprogenitor differentiation and bone formation. The mass of bioactive glass used in this study provides a comparable and potentially additive, response to localized VEGF delivery over early time points. These studies demonstrate a materials approach to achieve an angiogenic response formerly limited to the delivery of inductive growth factors.
Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
J Kent
JK
Leach
Darnell
D
Kaigler
Zhuo
Z
Wang
Paul H
PH
Krebsbach
David J
DJ
Mooney
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001808:Blood Vessels; D001861:Bone Regeneration; D001842:Bone and Bones / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005898:Glass; D006801:Humans; D066298:In Vitro Techniques; D008648:Mesoderm / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011108:Polymers / Q000737:chemistry; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism
D001672:Biocompatible Materials; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A