Intraoperative Optimization of Stromal Vascular Fraction for Remediation of Radiated Fracture Repair: Closing the Gap on Clinical Translation of Cell-Based Therapies.

BACKGROUND

Mechanical processing techniques to isolate the stromal vascular fraction (SVF) may optimize clinical translation of cell-based therapeutics. Therefore, the purpose of this study was to develop a technique for intraoperative isolation of SVF for immediate therapeutic use with the primary aim of enhancing bone healing at irradiated fracture sites.

METHODS

Male Lewis rats (n = 29) were divided into groups: fracture, radiation with fracture, and radiation with fracture and SVF implantation. Experimental groups received 35 Gy of targeted radiation. All groups underwent mandibular osteotomy and external fixation. SVF was isolated from inguinal fat pads using Tulip Sizing Transfers, serial filtration, and centrifugation. The resultant cell pellet was implanted at the osteotomy site. After 40 days, bone union and mineralization were evaluated based on gross pathology and micro-computed tomography, respectively, and biomechanical strength testing was performed.

RESULTS

SVF treatment increased union rates after radiation (79% vs 20%). Additionally, SVF improved both bone mineral density (666.2 ± 32.0 vs 312.2 ± 51.7; P = 0.000) and bone volume fraction (0.744 ± 0.072 vs 0.350 ± 0.041; P = 0.000) compared with the irradiated control. In fact, SVF treatment into irradiated fracture sites resulted in bone mineral density and bone volume fraction similar to the bone formed at nonirradiated fracture sites, as there was no significant difference between groups. SVF treatment did not significantly improve biomechanical strength compared with the irradiated control.

CONCLUSIONS

In this study, we developed a novel approach utilizing mechanical methods to enable intraoperative SVF isolation for immediate implantation. SVF demonstrates therapeutic potential for applications in irradiated fracture healing. The results of this study are promising for the long-awaited translation of cell-based therapeutics into the clinical arena.