S. S. Deshpande1, A. Zheutlin1, S. Kang2, T. Patel1, A. Donneys1, P. Felice1,3, N. Noah1, J. Rodriguez1, Y. Polyatskaya1, S. R. Buchman1 1University Of Michigan,Plastic Surgery,Ann Arbor, MI, USA 2University Of Michigan,Otolaryngology,Ann Arbor, MI, USA 3Medical University Of South Carolina,General Surgery,Charleston, Sc, USA
Introduction:
Radiation is known to be detrimental to bone and soft tissue repair, resulting in an unacceptably high incidence of devastating wound healing complications. This is effected through a mechanism of both direct cellular and vascular depletion. We sought to utilize bone marrow stromal cells (BMSCs), which have previously been shown to enhance the generation of new bone during distraction osteogenesis (DO), to remediate this deficiency. The purpose of this study was to allow for the successful utility of distraction osteogenesis in an irradiated field utilizing intra-operatively placed BMSCs for the purpose of craniofacial reconstruction in head and neck cancer victims.
Methods:
29 male Lewis rats were split into three groups, DO (n=10), XRT/DO (n=10) and BMSC (n=14). XRT and DO underwent 5 day fractionated XRT of the left mandible at 7 Gy per day and were allowed to recover for two weeks. All groups underwent mandibular distractor placement. The BMSC group received a Surgifoam scaffold with 2 million BMSCs intra-operatively placed within the distraction gap. Groups were distracted at 0.3mm every 12 hrs to a 5.1mm (a critical-sized defect for an irradiated, distracted mandible), and sacrificed on post-operative day 40. Coronal sections were obtained and stained using Hematoxylin & Eosin (H&E), Safranin O, and Gomori Trichrome. Statistical analysis was performed with ANOVA and subsequent Tukey or Games-Howell post-hoc tests, dependent on data heterogeneity.
Results:
Gomori Trichrome demonstrated a significantly increased osteocyte number (87.13 + 8.08 vs 67.86 + 9.47, p=0.000) and significantly decreased empty lacunae (2.17 + .62 vs 15.64 + 7.80, p=0.000) in BMSC compared to XRT/DO. There were no significant differences between DO and BMSC. Safranin O demonstrated no cartilage presence. H&E staining demonstrated more woven bone within the regenerate of DO as well as XRT/DO/PTH specimens.
Conclusion:
The vascular environment of bone is essential for its capacity to heal. We demonstrated both qualitative and quantitative metrics of radiation-induced remediation of cellularity utilizing bone marrow stromal cells, demonstrating its potential for use in irradiated fields. BMSC therapy was able to remediate the detriments to osteocyte number as well as prevent empty lacunae formation. Furthermore, BMSCs stimulated new osteoid growth, as established by H&E. Finally, BMSCs maintains the intramembranous healing mechanism intrinsic to DO, as the Safranin O stain showed no evidence of a cartilaginous intermediate. As such, this abstract has demonstrated that intra-operatively placed BMSC therapy is a powerful tool for remediating the damage of radiation and allowing for successful utilization of distraction osteogenesis.
