title: Vascular analysis as a proxy for mechanostransduction response in an isogenic, irradiated murine model of mandibular distraction osteogenesis.
abstract: BACKGROUND
  Head and neck cancer is a debilitating and disfiguring disease. Although numerous treatment options exist, an array of debilitating side effects accompany them, causing physiological and social problems. Distraction osteogenesis (DO) can avoid many of the pathologies of current reconstructive strategies; however, due to the deleterious effects of radiation on bone vascularity, DO is generally ineffective. This makes investigating the effects of radiation on neovasculature during DO and creating quantifiable metrics to gauge the success of future therapies vital. The purpose of this study was to develop a novel isogenic rat model of impaired vasculogenesis of the regenerate mandible in order to determine quantifiable metrics of vascular injury and associated damage.
  
  
  METHODS
  Male Lewis rats were divided into two groups: DO only (n=5) AND Radiation Therapy (XRT)+DO (n=7). Afterwards, a distraction device was surgically implanted into the mandible. Finally, they were distracted a total of 5.1mm. Animals were perfused with a radiopaque casting agent concomitant with euthanasia, and subsequently demineralization, microcomputed tomography, and vascular analysis were performed.
  
  
  RESULTS
  Vessel volume fraction, vessel thickness, vessel number, and degree of anisotropy were diminished by radiation. Vessel separation was increased by radiation.
  
  
  CONCLUSIONS
  The DO group experienced vigorous vessel formation during distraction and neovascularization with a clear, directional progression, while the XRT/DO group saw weak vessel formation during distraction and neovascularization. Further studies are warranted to more deeply examine the impairments in osteogenic mechanotransductive pathways following radiation in the murine mandible. This isogenic model provides quantifiable metrics for future studies requiring a controlled approach to immunogenicity.
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States; Department of Otolaryngology, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Kang
authors.affiliation: College of Literature, Science, and Arts, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Page
authors.affiliation: Department of General Surgery, University of South Carolina, Charleston, SC, United States.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Felice
authors.affiliation: College of Literature, Science, and Arts, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Kiryakoza
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States; Kalamazoo College, Kalamazoo, MI, United States.
authors.forename: Samir S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Craniofacial Research Laboratory, University of Michigan Health System, Ann Arbor, MI, United States; Section of Plastic Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, MI, United States. Electronic address: sbuchman@umich.edu.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000009:adverse effects; D008297:Male; D008334:Mandible / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000528:radiation effects* / Q000601:surgery*; D040542:Mechanotransduction, Cellular / Q000528:radiation effects*; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D019857:Osteogenesis, Distraction / Q000009:adverse effects / Q000379:methods*; D018714:Radiotherapy, Adjuvant; D011917:Rats, Inbred Lew; D013997:Time Factors; D055114:X-Ray Microtomography
keywords: Angiogenesis; Distraction osteogenesis; Head and neck cancer; Isogenic; Mechanotransduction; Radiation therapy; Tissue engineering; Vasculogenesis