VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

Wernike, E; Montjovent, MO; Liu, Y; Wismeijer, D; Hunziker, EB; Siebenrock, KA; Hofstetter, W; Klenke, FM (2010). VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo. European cells & materials eCM, 19, pp. 30-40. Aberystwyth (UK): University of Wales

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Bone formation and osseointegration of biomaterials are dependent on angiogenesis and vascularization. Angiogenic growth factors such as vascular endothelial growth factor (VEGF) were shown to promote biomaterial vascularization and enhance bone formation. However, high local concentrations of VEGF induce the formation of malformed, nonfunctional vessels. We hypothesized that a continuous delivery of low concentrations of VEGF from calcium phosphate ceramics may increase the efficacy of VEGF administration.VEGF was co-precipitated onto biphasic calcium phosphate (BCP) ceramics to achieve a sustained release of the growth factor. The co-precipitation efficacy and the release kinetics of the protein were investigated in vitro. For in vivo investigations BCP ceramics were implanted into critical size cranial defects in Balb/c mice. Angiogenesis and microvascularization were investigated over 28 days by means of intravital microscopy. The formation of new bone was determined histomorphometrically. Co-precipitation reduced the burst release of VEGF. Furthermore, a sustained, cell-mediated release of low concentrations of VEGF from BCP ceramics was mediated by resorbing osteoclasts. In vivo, sustained delivery of VEGF achieved by protein co-precipitation promoted biomaterial vascularization, osseointegration, and bone formation. Short-term release of VEGF following superficial adsorption resulted in a temporally restricted promotion of angiogenesis and did not enhance bone formation. The release kinetics of VEGF appears to be an important factor in the promotion of biomaterial vascularization and bone formation. Sustained release of VEGF increased the efficacy of VEGF delivery demonstrating that a prolonged bioavailability of low concentrations of VEGF is beneficial for bone regeneration.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Center of Regenerative Medicine for Skeletal Tissues (discontinued)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Center of Regenerative Medicine for Skeletal Tissues (discontinued)

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery

UniBE Contributor:

Wernike, Ellen; Montjovent, Marc-Oliver; Liu, Yuelian; Hunziker, Ernst Bruno; Siebenrock, Klaus-Arno; Hofstetter, Willy and Klenke, Frank M.

ISSN:

1473-2262

Publisher:

University of Wales

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

16 Jul 2018 13:05

PubMed ID:

20178096

Web of Science ID:

000278752500001

URI:

https://boris.unibe.ch/id/eprint/114 (FactScience: 196029)

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