TY - JOUR
T1 - 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
AU - Larsen, Mikko
AU - Willems, Wouter F.
AU - Pelzer, Michael
AU - Friedrich, Patricia F.
AU - Yaszemski, Michael J.
AU - Bishop, Allen T.
PY - 2010/8
Y1 - 2010/8
N2 - 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+VEGFgroup (35.1%) than control (13.9%) (p<0.05),and a linear trendwasfound from control,FGF,VEGF,toFGF+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.
AB - 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+VEGFgroup (35.1%) than control (13.9%) (p<0.05),and a linear trendwasfound from control,FGF,VEGF,toFGF+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.
KW - Allotransplantation
KW - Bone
KW - FGF
KW - Microspheres
KW - VEGF
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U2 - 10.1002/jor.21098
DO - 10.1002/jor.21098
M3 - Article
C2 - 20162714
AN - SCOPUS:77954696812
SN - 0736-0266
VL - 28
SP - 1015
EP - 1021
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 8
ER -