Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF-2 and VEGF

Wouter F. Willems, Mikko Larsen, Guilherme Giusti, Patricia F. Friedrich, Allen Thorp Bishop

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Frozen bone allografts are susceptible to nonunion and fracture due to limited revascularization and incomplete bone remodeling. We aim to revascularize bone allografts by combining angiogenesis from implanted arteriovenous (AV) bundles with delivery of fibroblast growth factor (FGF-2) and/or vascular endothelial growth factor (VEGF) via biodegradable microspheres. Rat femoral diaphyseal allografts were frozen at -80°C, and heterotopically transplanted over a major histocompatibility mismatch. A saphenous AV bundle was inserted into the intramedullary canal. Growth factor was encapsulated into microspheres and inserted into the graft, providing localized and sustained drug release. Forty rats were included in four groups: (I) phosphate-buffered saline, (II) FGF-2, (III) VEGF, and (IV) FGF-2 + VEGF. At 4 weeks, angiogenesis was measured by the hydrogen washout method and microangiography. Bone remodeling was evaluated by quantitative histomorphometry and histology. Bone blood flow was significantly higher in groups III and IV compared to control (p < 0.05). Similarly, bone remodeling was higher in VEGF groups. FGF-2 had little effect on allograft revascularization. No synergistic effect was observed with use of both cytokines. Delivered in microspheres, VEGF proved to be a potent angiogenic cytokine, increasing cortical bone blood flow and new bone formation in frozen allografts revascularized with an implanted AV bundle.

Original languageEnglish (US)
Pages (from-to)1431-1436
Number of pages6
JournalJournal of Orthopaedic Research
Volume29
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Bone Remodeling
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Allografts
Microspheres
Bone and Bones
Cytokines
Histocompatibility
Thigh
Osteogenesis
Hydrogen
Intercellular Signaling Peptides and Proteins
Histology
Phosphates
Transplants

Keywords

  • allograft
  • angiogenesis
  • FGF-2
  • osteogenesis
  • VEGF

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF-2 and VEGF. / Willems, Wouter F.; Larsen, Mikko; Giusti, Guilherme; Friedrich, Patricia F.; Bishop, Allen Thorp.

In: Journal of Orthopaedic Research, Vol. 29, No. 9, 09.2011, p. 1431-1436.

Research output: Contribution to journalArticle

Willems, Wouter F. ; Larsen, Mikko ; Giusti, Guilherme ; Friedrich, Patricia F. ; Bishop, Allen Thorp. / Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF-2 and VEGF. In: Journal of Orthopaedic Research. 2011 ; Vol. 29, No. 9. pp. 1431-1436.
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