Revitalizing Structural Cryopreserved Allografts in a Porcine Tibia Defect Model

Introduction 

The treatment of segmental bone defects remains challenging as complications frequently occur with the currently available methods, including vascularized autograft, prosthetic replacement, bone transport and cryopreserved bone allograft (CBA). Although the use of CBA is comparatively simple, it lacks donor site morbidity and provides immediate stability, however the grafts remain largely avascular resulting in high failure rates due to nonunion, infection and stress fractures. Revitalizing the CBA has the potential to solve these problems. Previous studies in small animal models have shown the use of surgical revascularization to induce neo-angiogenesis and improve bone viability in the CBA. The purpose of this study is to investigate if surgical revascularization enhances bone circulation and bone remodeling in a tibial defect-orthotopic reconstruction model, placing a cryopreserved allograft in a Yucatan mini Pig.

 

Material & Methods

Cryopreserved tibial bone allografts were transplanted in swine leukocyte antigen (SLA) mismatched Yucatan minipigs after creating a 3.5cm segmental bone defect in the tibia. The anterior tibial arteriovenous bundle (AV-bundle) was inserted into the intramedullary canal. Eight pigs received a patent AV-bundle (revascularized group), 8 pigs received a proximally ligated AV-bundle (control group) and the contralateral side was used as an untreated control. The graft was fixated with a locking compression plate to provide a weight bearing construction. After 20 weeks, the pigs were sacrificed and the tibia was removed and analyzed. Neo-angiognesis was evaluated by quantifying vascular volumes using the micro-CT. Bone remodeling was measured by quantitative histomorphometry and micro-computed tomography.

Results

Seven of 8 AV-bundles in the revascularized group were patent, and 1 thrombosed due to allograft displacement. Total vascular volume was higher in the revascularized allografts (127 mm³) compared to both the control group (55 mm³, p=0.015) and the contralateral side (29 mm³, p=0.015). All patent bundles showed neovascularization extending into the cortical bone. Revascularized allografts had increased bone remodeling in the inner cortical area of the graft compared to the non-revascularized grafts (Bone Formation Rate: 381 ± 64 μm³/ μm³/ year versus 299 ± 143 μm³/ μm³/ year, p=0.05).

Conclusion

Surgical revascularization of porcine tibial CBAs by implantation of an AV-bundle creates an enhanced autogenous neoangiogenic circulation and accelerates active bone formation in the inner cortical area.