Bone regeneration via a mineral substrate and induced angiogenesis.
Angiogenesis and biomineral substrates play major roles in bone development and regeneration. We hypothesized that macroporous scaffolds of biomineralized 85:15 poly(lactide-co-glycolide), which locally release vascular endothelial growth factor-165 (VEGF), would direct simultaneous regeneration of bone and vascular tissue. The presence of a bone-like biomineral substrate significantly increased regeneration of osteoid matrix (32 +/- 7% of total tissue area; mean +/- SD; p < 0.05) and mineralized tissue (14 +/- 2%; P < 0.05) within a rat cranium critical defect compared with a non-mineralized polymer scaffold (19 +/- 8% osteoid and 10 +/- 2% mineralized tissue). Further, the addition of VEGF to a mineralized substrate significantly increased the generation of mineralized tissue (19 +/- 4%; P < 0.05) compared with mineralized substrate alone. This appeared to be due to a significant increase in vascularization throughout VEGF-releasing scaffolds (52 +/- 9 vessels/mm(2); P < 0.05) compared with mineralized scaffolds without VEGF (34 +/- 4 vessels/mm(2)). Surprisingly, there was no significant difference in total osteoid between the two samples, suggesting that increased vascularization enhances mineralized tissue generation, but not necessarily osteoid formation. These results indicate that induced angiogenesis can enhance tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.
Murphy
W L
WL
Department of Biomedical Engineering, University of Michigan, 5213 Dental, 1011 North University Avenue, Ann Arbor, MI 48109-1078, USA.
Simmons
C A
CA
Kaigler
D
D
Mooney
D J
DJ
D000704:Analysis of Variance; D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D001847:Bone Diseases / Q000503:physiopathology / Q000601:surgery; D001857:Bone Matrix / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D004337:Drug Carriers; D019344:Lactic Acid; D008903:Minerals / Q000627:therapeutic use*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D011917:Rats, Inbred Lew; D012886:Skull / Q000098:blood supply / Q000187:drug effects; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000032:analysis
D001672:Biocompatible Materials; D004337:Drug Carriers; D008903:Minerals; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid