Vascular endothelial growth factor for in vivo bone formation: Asystematic review

Chris Halling Dreyer*, Kristian Kjærgaard, Ming Ding, L Qin

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Background:To achieve optimal bone formation one of the most influential parameters has been mentioned to beadequate blood supply. Vascular endothelial growth factor (VEGF) is hereby of particular interest in boneregeneration, because of its primary ability to induce neovascularization and chemokine affection for endothelialcells (EC), and is considered to be the main regulator of vascular formation. However, the growth factor has yet tobe implemented in a clinical setting in orthopaedic intervention surgery. We hypothesised that the developmentof VEGF in vivo for bone formation in the last decade had progressed towards clinical application since the latestsystematic review from 2008.Objective:This systematic review recapped the last 13 years of in vivo bone regeneration using vascular endo-thelial growth factor (VEGF).Method:A total of 1374 articles were identified using the PubMed search string(vegf or“vascular endothelial growthfactor”) and (osteogen* or“bone formation”or“bone regeneration”). By 3 selection phases 24 published articleswere included by the criteria of being in vivo, using only VEGF for bone formation, published after 2007 andwritten in English. Articles in vitro, written in different languages than English and older than 2007 was excluded.The most recent systematic review on this subject was published in 2008, with the latest included study from 01to 11-2007. All included studies were classified based on animal, type of defect, scaffold, control group, type ofVEGF, release rate, dosage of VEGF, time of evaluation and results. Each study was evaluated for risk of bias bymodified CAMARADES quality assessment for the use in experimental animal studies. The score was calculated bypeer review journal publication, use of control group, randomisation of groups, justified VEGF dosage, blinding ofresults, details on animal model, sample size calculation, comply with ethics and no conflict of interest.Results:No clinical trials or human application studies were obtained from our search. Experimentally, 11 articlesusing solely VEGF for bone formation had a group or a timepoint significantly better than the correspondingcontrol group. 18 articles revealed no significant difference of VEGF compared to the control group and 1 articlereported a significant decreased bone growth using VEGF compared to control.Conclusion:Based on these results no clinical studies have yet been performed. However, indications in the bestuse of VEGF from experimental studies could be made towards that the optimal release is within thefirst threeweeks, in defect models, with the best effect before eight weeks. Future designs should incorporate this withstandardised and reproducible models for verification towards clinical practice.The translational potential of this article:This systematic review aims to assess the existing literature to focus onmethodologies and outcomes that can provide future knowledge regarding the solitary use of VEGF for boneregeneration in a clinical setting.
Original languageEnglish
JournalJournal of Orthopaedic Translation
Pages (from-to)46-57
Publication statusPublished - Sep 2020


  • Angiogenesis
  • Biomaterials
  • Growth factors
  • Osteogenesis
  • Tissue engineering
  • Vascular endothelial growth factor

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