Growth and transplantation of a custom vascularised bone graft in a man

Summary

Background

A major goal of research in bone transplantation is the ability to avoid creation of secondary bone defects. We aimed to repair an extended mandibular discontinuity defect by growth of a custom bone transplant inside the latissimus dorsi muscle of an adult male patient.

Methods

Three-dimensional computed tomography (CT) scanning and computer-aided design techniques were used to produce an ideal virtual replacement for the mandibular defect. These data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 and 20 mL of the patient's bone marrow. Thus prepared, the transplant was implanted into the latissimus dorsi muscle and 7 weeks later transplanted as a free bone-muscle flap to repair the mandibular defect.

Findings

In-vivo skeletal scintigraphy showed bone remodelling and mineralisation inside the mandibular transplant both before and after transplantation. CT provided radiological evidence of new bone formation. Postoperatively, the patient had an improved degree of mastication and was satisfied with the aesthetic outcome of the procedure.

Interpretation

Heterotopic bone induction to form a mandibular replacement inside the latissimus dorsi muscle in a human being is possible. This technique allows for a lower operative burden compared with conventional techniques by avoiding creation of a secondary bone defect. It also provides a good three-dimensional outcome.

Introduction

Ever since the Vacanti research group revealed the mouse with a human ear on its back in 1997,¹ worldwide interest in tissue engineering and prefabrication techniques has grown. This technology might eventually allow us to produce substitute organs or body parts inside human bodies.2, 3 Success could make the search for organ donors, and the well-described difficulties associated with allogenic organ transplants, redundant.

Research by us has focused on new approaches to find replacements for bone defects, especially for important size defects of the mandible.4, 5, 6, 7 Today, a mandible with a major discontinuity defect of more than 5 cm can be repaired with an autologous vascularised fibula, scapula, iliac crest, or rib transplant, which is sometimes necessary after ablative tumour surgery. These bone transplantation techniques are clinically approved and are being successfully undertaken in cancer surgery centres worldwide. However, a major disadvantage of this technique is that the process of harvesting these bone grafts always creates another skeletal defect, which itself is associated with serious morbidity. In 2001, we showed a flap prefabrication technique in a minipig-model4, 5, 6 that circumvented the need for creation of a second skeletal defect through bone harvesting.

BMP7 is an osteoinductive factor that initiates conversion of undifferentiated precursor stem cells into osteoprogenitor cells, which produce mature bone.5, 6, 7, 8, 9 With Therapeutic Goods Administration approval (Department of Health and Ageing, Australia) of recombinant human BMP7 for human use in 2001,9, 10 prefabrication of bone grafts for reconstruction after tumour surgery has become a possibility.

A 56-year-old man, who had received ablative tumour surgery 8 years previously in the form of a subtotal mandibulectomy, asked us to reconstruct his mandible, which had been resected from paramedian left region to the retromolar right region. This important size defect of more than 7 cm had been bridged with a titanium reconstruction plate since initial surgery (figure 1). His head and neck region had been further compromised by radiation treatment given at the time (total dose 66 Gy). Because he had been given warfarin for an aortic valve replacement we had to keep bony defects to a minimum to avoid major postoperative bleeding. To prevent creation of a donor-site bone defect, the patient was selected for the bone-muscle-flap prefabrication technique. The aim was to grow a subtotal replacement mandible inside the latissimus muscle with full bony continuity and an adequate vessel pedicle to allow for subsequent transplantation of a viable graft into the defect. Furthermore, we aimed to ensure that the replacement should be individually shaped to fit the defect perfectly, thus improving the chances of adequate postoperative function and a satisfactory aesthetic result.