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

Mikko Larsen, Wouter F. Willems, Michael Pelzer, Patricia F. Friedrich, Michael J Yaszemski, Allen Thorp Bishop

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18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1015-1021
Number of pages7
JournalJournal of Orthopaedic Research
Volume28
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Fibroblast Growth Factor 2
Fibroblast Growth Factors
Vascular Endothelial Growth Factor A
Bone and Bones
Microspheres
Osteogenesis
Immunosuppression
Blood Vessels
Homologous Transplantation
Tacrolimus
Thigh
Blood Donors
Allografts
Hydrogen
Histology
Buffers
Cytokines
Transplants

Keywords

  • Allotransplantation
  • Bone
  • FGF
  • Microspheres
  • VEGF

ASJC Scopus subject areas

  • Medicine(all)
  • Orthopedics and Sports Medicine

Cite this

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title = "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",
abstract = "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.",
keywords = "Allotransplantation, Bone, FGF, Microspheres, VEGF",
author = "Mikko Larsen and Willems, {Wouter F.} and Michael Pelzer and Friedrich, {Patricia F.} and Yaszemski, {Michael J} and Bishop, {Allen Thorp}",
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AU - Larsen, Mikko

AU - Willems, Wouter F.

AU - Pelzer, Michael

AU - Friedrich, Patricia F.

AU - Yaszemski, Michael J

AU - Bishop, Allen Thorp

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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.

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