Neoangiogenesis from Implanted Blood Vessels of Donor Origin Maintains Blood Flow in a Vascularized Bone Allograft after Removal of Immunosuppression

Large skeletal defects resulting from tumors, infection, or failed arthroplasty present a reconstructive challenge. Available methods have limitations. Structural allografts are incompletely revascularized, and are prone to nonunion and late stress fracture. Vascularized autografts provide the ability to heal and remodel with stress, but are frequently of insufficient size and strength. Prosthetic replacement of diaphyseal bone may fail, loosen, or produce periprosthetic fractures. Transplantation of living allogenic bone would provide a replacement closely matched to the dimensions and mechanical properties of the resected bone, combined with the desirable healing properties of a vascularized autograft. Vascularized bone allotransplantation without the health risks of immunosuppressive drugs or tolerance induction would be an important advance.

The authors proposed a novel method by which this may be accomplished: microsurgical bone transfer with development of a new host-derived osseous blood supply. Immunosuppression needs only to allow sufficient time for angiogenesis to occur.

Two groups of 30 PVG rats underwent microsurgical femoral transplantation from DA donors. The femoral vessels were anastomosed and the contralateral saphenous artery and vein were implanted longitudinally through the medullary canal as an arteriovenous pedicle. This was ligated proximal to the bone in 15 rats. A reinforced silicone membrane was wrapped around the bone to prevent angiogenesis from surrounding tissues. FK-506 was administered daily for 14 days. At 18 weeks, skin grafts from DA, PVG, and Lewis rats were placed. At 21 weeks, blood flow in the cortex of the bone grafts was measured using the hydrogen washout method.

Blood flow in the patent a∕v pedicle group was 3.2 ± 2.0 ml∕min∕100 g; no flow values could be obtained in the ligated group (p = 0). All PVG skin grafts healed (94 ± 6% area); all DA and Lewis grafts were rejected (100% area). Capillary density measurements were correlated with blood flow values (r = 0.70; p < 0.0001). Two a∕v pedicles were thrombosed at sacrifice (93% patency rate).

Neoangiogenesis from implanted blood vessels of donor origin maintains blood flow in a vascularized bone allograft after removal of immunosuppression and in the absence of tolerance. Implanted a∕v pedicles maintain patency in a small animal model.