Living musculoskeletal allotransplants currently require long-term immunosuppression to maintain viability, impractical due to associated risks for non-life-critical tissue transplantation. We have previously demonstrated an alternative method using implanted host-derived vessels to replace the allogeneic nutrient circulation. These vessels maintain measurable blood flow, generate extensive neoangiogeneic capillaries and form new bone when combined with short-term immunosuppression. In this study, we have used this method to reconstruct large segmental femoral defects.

A segmental femoral defect was created in Dutch-Belted rabbits. Reconstruction was performed using a free vascularized allogeneic femoral diaphyseal transplant from a New Zealand White rabbit. Rigid fixation allowing immediate full weight-bearing was performed. In addition to microvascular repair of the nutrient artery circulation, a pedicled inferior epigastric fascial flap was placed within the medullary canal. Survival time was 16 weeks.

Five groups of 10 Dutch-Belted rabbits each included a pedicled autotransplant control group, and four allotransplant groups which varied in fascial flap patency (patent or ligated) and immunosuppression with 0.08 mg/kg Tacrolimus (+ or -). Healing was quantified by X-ray. Microangiography and Spalteholz bone clearing allowed quantification of neoangiogenesis. Mechanical properties were evaluated using 4-point bending. Quantitative histomorphometry assessed bone remodeling.

X-ray analysis using a grading schema demonstrated an equivalent healing response when autotransplant controls were compared to immunosuppressed allotransplants with patent fascial flaps. The roentgenograms of the latter group demonstrated faster healing as well as the lowest relative ultimate strength and elastic modulus values of all groups. This is an indication of biologic activity, including a greater blood supply and a higher rate of bone remodeling than other animals. It correlated with findings from microangiography (the highest amount of neoangiogenesis among all groups) and histomorphometric analysis of bone turnover. Not surprisingly, the lowest angiogenesis and bone remodeling values were found in the non-immunosuppressed allotransplant femurs with a ligated intramedullary flap.

Surgical angiogenesis from host-derived fascial flaps can provide greater blood flow and improved rates/grading of healing in immunosuppressed allogeneic bone transplants than other groups. Material properties of this group were also less than the other groups. Thus, while the vascularized tissue allotransplants treated with immunosuppression and fascial flap implantation maintained flow and viability at levels higher than other groups, we found this to weaken the transplant more as well. As the demonstrated active bone turnover ultimately replaces the transplant with host-derived cells, this process in the long-term may result in a more stable transplant with minor rejection.