Intraoperative Stromal Vascular Fraction Therapy Improves Histomorphometric and Vascular Outcomes in Irradiated Mandibular Fracture Repair

Abstract

Background: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction. Methods: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment. Irradiated groups received a fractioned dose of 35 Gy before mandibular osteotomy. Stromal vascular fraction was harvested from the inguinal fat of isogenic donors, centrifuged, and placed intraoperatively into the osteotomy site. All mandibles were evaluated for bony union and vascularity using micro–computed tomography before histologic analysis. Results: Union rates were significantly improved in the irradiated fracture with stromal vascular fraction treatment group (82 percent) compared to the irradiated fracture group (25 percent) and were not statistically different from the fracture group (100 percent). Stromal vascular fraction therapy significantly improved all metrics of bone vascularization compared to the irradiated fracture group and was not statistically different from fracture. Osteocyte proliferation and mature bone formation were significantly reduced in the irradiated fracture group. Bone cellularity and maturity were restored to nonirradiated levels in the irradiated fracture with stromal vascular fraction treatment group despite preoperative irradiation. Conclusions: Vascular and cellular depletion represent principal obstacles in the reconstruction of irradiated bone. This study demonstrates the efficacy of stromal vascular fraction therapy in remediating these damaging effects and provides a promising foundation for future studies aimed at developing noncultured, cell-based therapies for clinical implementation.

Therapeutic Efficacy of Adipose-Derived Stem Cells Versus Bone Marrow Stromal Cells for Irradiated Mandibular Fracture Repair

“…9 Given our laboratory's longstanding interest in the vascular component of fracture healing, we have previously evaluated the ability of both ASCs and BMSCs to restore the vascular network in irradiated bone. 23,25 The present study extends our knowledge of mesenchymal stem cells by demonstrating that ASCs induce a stronger vascular response in irradiated bone compared with BMSCs. Indeed, the results of this study support our hypothesis that the predominantly vascular platform utilized by ASCs is superior to the chiefly bony platform utilized by BMSCs, as evidenced by significantly improved vascularity as well as increased union rate and a trend toward increased biomechanical strength within the ASC experimental group.…”

“…The ASC group demonstrated a 92% union rate, whereas the BMSC group demonstrated a 75% union rate. These results represent a 3- to 4-fold increase in union rate compared with historical union rates of radiated control groups in our laboratory 22–24 …”

“…Animals were allowed a 40-day recovery period before they were killed to approximate a 6-week period of bone healing that is commonly recommended following bone fractures clinically. Importantly, our laboratory has previously demonstrated the ability of both ASC and BMSC experimental regimens to improve these metrics compared with radiated control groups 22–26 …”

“…Bony union was defined as solid bone bridging and absence of motion across the fracture site on gross manipulation. This definition has been previously described and utilized by our laboratory 22,23 …”

“…However, relatively few studies have examined the ability of ASCs and BMSCs to augment healing and regeneration in irradiated bone. Over the past 10 years, our laboratory has presented a series of experiments demonstrating the ability of ASCs to improve the biomechanical strength and vascularity of bone in a murine model of irradiated mandibular fracture repair 22,23 . Our laboratory has also demonstrated that BMSCs improve the mineralization and cellularity of regenerate bone in a murine model of irradiated distraction osteogenesis 24–26 .…”