Augmentation of surgical angiogenesis in vascularized bone allotransplants with host-derived a/v bundle implantation, fibroblast growth factor-2, and vascular endothelial growth factor administration.
We have previously shown experimental transplantation of living allogeneic bone to be feasible without long-term immunosuppression by development of a recipient-derived neoangiogenic circulation within bone. In this study, we examine the role of angiogenic cytokine delivery with biodegradable microspheres to enhance this process. Microsurgical femoral allotransplantation was performed from Dark Agouti to Piebald Virol Glaxo rats. Poly(D,L-lactide-co-glycolide) microspheres loaded with buffer, basic fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), or both, were inserted intramedullarly along with a recipient-derived arteriovenous (a/v) bundle. FK-506 was administered daily for 14 days, then discontinued. At 28 days, bone blood flow was measured using hydrogen washout. Microangiography, histologic, and histomorphometric analyses were performed. Capillary density was greater in the FGF+VEGF group (35.1%) than control (13.9%) (p < 0.05), and a linear trend was found from control, FGF, VEGF, to FGF+VEGF (p < 0.005). Bone formation rates were greater with VEGF (p < 0.01) and FGF+VEGF (p < 0.05). VEGF or FGF alone increased blood flow more than when combined. Histology rejection grading was low in all grafts. Local administration of vascular and fibroblast growth factors augments angiogenesis, bone formation, and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts after removal of immunosuppression.
Larsen
Mikko
M
Department of Plastic and Reconstructive Surgery, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Willems
Wouter F
WF
Pelzer
Michael
M
Friedrich
Patricia F
PF
Yaszemski
Michael J
MJ
Bishop
Allen T
AT
D000818:Animals; D001861:Bone Regeneration; D016025:Bone Transplantation; D005260:Female; D005269:Femur / Q000098:blood supply*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D007083:Iliac Artery / Q000637:transplantation*; D007084:Iliac Vein / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016559:Tacrolimus