Alexander R Zheutlin1, Sagar S Deshpande1, Noah S Nelson2, Yekaterina Polyatskaya3, Jose J Rodriguez2, Alexis Donneys2, Steven R Buchman4. 1. Medical Student, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. 2. Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. 3. Resident, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. 4. Professor in Plastic Surgery, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. Electronic address: sbuchman@med.umich.edu.
Abstract
PURPOSE: The devastation radiation therapy (XRT) causes to endogenous tissue in patients with head and neck cancer can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. This study investigated the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). The authors posited that radiation would result in fewer osteocytes, with increased empty lacunae and immature osteoid. MATERIALS AND METHODS: Twenty Lewis rats were randomly assigned to a DO group (n = 10) or a XRT/DO group (n = 10). These groups underwent an osteotomy and mandibular DO across a 5.1-mm gap. XRT was administered to the XRT/DO group at a fractionated human equivalent dose of 35 Gy before surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histologic analysis. RESULTS: Bone that underwent radiation showed a significantly decreased osteocyte count and complementary increase in empty lacunae compared with non-XRT bone (P = .019 and P = .000). In addition, XRT bone exhibited increased immature osteoid and decreased mature woven bone compared with nonradiated bone (P = .001 and P = .003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further showing the devastating damage from XRT (P = .001). CONCLUSION: These results clearly show the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork on which to investigate cellular therapies in an immuno-privileged model of mandibular DO.
PURPOSE: The devastation radiation therapy (XRT) causes to endogenous tissue in patients with head and neck cancer can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. This study investigated the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). The authors posited that radiation would result in fewer osteocytes, with increased empty lacunae and immature osteoid. MATERIALS AND METHODS: Twenty Lewis rats were randomly assigned to a DO group (n = 10) or a XRT/DO group (n = 10). These groups underwent an osteotomy and mandibular DO across a 5.1-mm gap. XRT was administered to the XRT/DO group at a fractionated human equivalent dose of 35 Gy before surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histologic analysis. RESULTS: Bone that underwent radiation showed a significantly decreased osteocyte count and complementary increase in empty lacunae compared with non-XRT bone (P = .019 and P = .000). In addition, XRT bone exhibited increased immature osteoid and decreased mature woven bone compared with nonradiated bone (P = .001 and P = .003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further showing the devastating damage from XRT (P = .001). CONCLUSION: These results clearly show the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork on which to investigate cellular therapies in an immuno-privileged model of mandibular DO.
Authors: Sagar S Deshpande; Kathleen K Gallagher; Alexis Donneys; Catherine N Tchanque-Fossuo; Deniz Sarhaddi; Hongli Sun; Paul H Krebsbach; Steven R Buchman Journal: Stem Cells Dev Date: 2013-02-19 Impact factor: 3.272
Authors: Steven R Buchman; Michael A Ignelzi; Caius Radu; Jonathan Wilensky; Andrew H Rosenthal; Lawrence Tong; Samuel T Rhee; Steven A Goldstein Journal: Ann Plast Surg Date: 2002-11 Impact factor: 1.539
Authors: Sagar S Deshpande; Kathleen K Gallagher; Alexis Donneys; Noah S Nelson; Nicholas P Guys; Peter A Felice; Erin E Page; Hongli Sun; Paul H Krebsbach; Steven R Buchman Journal: Plast Reconstr Surg Date: 2015-03 Impact factor: 4.730
Authors: M E Dudziak; P B Saadeh; B J Mehrara; D S Steinbrech; J A Greenwald; G K Gittes; M T Longaker Journal: Plast Reconstr Surg Date: 2000-10 Impact factor: 4.730
Authors: Sagar S Deshpande; Alexis Donneys; Stephen Y Kang; Erin E Page; Peter A Felice; Lauren Kiryakoza; Noah S Nelson; Jose Rodriguez; Samir S Deshpande; Steven R Buchman Journal: Microvasc Res Date: 2014-08-27 Impact factor: 3.514
Authors: Stephen Y Kang; Sagar S Deshpande; Alexis Donneys; Jose J Rodriguez; Noah S Nelson; Peter A Felice; Douglas B Chepeha; Steven R Buchman Journal: Bone Date: 2013-05-01 Impact factor: 4.398