Endocultivation: Computer-Aided Tissue Engineering of Customized, Vascularized Bone Grafts for Mandibular Reconstruction

P. H. WARNKE

EDITORIAL COMMENT

At present, the standard for mandibular reconstruction, either segmental or, at times, complete, is the use of vascularized fibula, scapula, or iliac crest. The failures are often due to poor lining, particularly in cases of prior irradiation.

The method here described, as the author indicates, is still experimental, but it brings together two principles that are fairly well established. One is the use of the prefabricated flap introduced by Shintomi, from Japan, and the second is the use of computerized technology for preoperative planning. It is still unclear what type of bone regeneration occurs with bone morphogenetic protein-7 in a scaffold made of titanium.

Currently, major bone discontinuity defects of more than 6 cm are repaired with an autologous vascularized fibula, scapula, iliac crest, or rib transplant. Recent advances in the emerging field of regenerative medicine, that is, repairing damaged tissue through growing it anew by means of tissue engineering, may offer new solutions for reconstructive surgeons. “Regeneration” means that one repairs the damaged tissue by growing it anew with methods of tissue engineering, thus circumventing the issue of immunologic rejection, as the patient’s own cells are used to cultivate the required tissue. I describe a technique of endocultivation, which involves the growing of customized, computer-designed, vascularized replacements for subsequent transfer, to reconstruct previously resected bone. It should be emphasized that endocultivation techniques are still at a basic stage of development and are currently more suited to homogenous tissue like bone. However, they may offer the potential to grow more complex organ replacements in the future.

INDICATIONS

The repair of bony defects from congenital malformations, trauma, infection, or tumor resection remains a challenge in modern orthopaedic and maxillofacial surgical practice (1). The reconstruction of the long bones, the spine, and the skull must meet high mechanical and aesthetic demands. However, a major disadvantage of autologous vascularized bone is that harvesting the required bone graft creates another skeletal defect, which is associated with significant morbidity (2). In vitro tissue engineering has been a focus of many research groups; however, in vivo endocultivation techniques currently offer greater potential (3, 4). Patients serve as their own bioreactors, and the required tissue is cultivated inside the patient’s own body on an individualized matrix. In vitro bioreactors are not required (4, 5, 6).

In 2004, we began using endocultivation techniques to grow customized, computer-designed, vascularized, jaw replacements in the latissimus dorsi muscle of patients, for subsequent transplantation to reconstruct their previously resected jaws (4, 5). The latissimus dorsi flap has accrued a broad spectrum of applications in the field of reconstructive surgery. This is due to the large area of tissue available, thereby allowing flexibility in flap design, as well as its long and high-capacity vascular pedicle that permits relatively technically easy microvascular anastomoses (7, 8).

The anatomic proximity of the latissimus dorsi to the thoracodorsal artery is fortuitous, as it allows for significant spontaneous neovascularization (9). This subsequently permits free-flap transfer into the desired recipient region. This independent vascular supply makes it possible to grow constructs of the size of a mandible or, in the future (4, 5), possibly even a complex organ. For example, the latissimus dorsi is a more suitable incubation site to grow a bone replacement, such as a neomandible, than the site to which it will subsequently be transplanted, as the area containing the bone defect is often compromised by prior radiation therapy. Irradiated tissue demonstrates poor regenerative properties and even soft-tissue injury heals poorly. The choice of a prepared muscle pouch inside the latissimus dorsi has proven
to be a highly successful site as a bioreactor in early clinical studies, with substantial evidence of heterotopic bone growth and remodeling within the graft (5).

The special feature of the endocultivation procedure is that the flap can be prefabricated with an individualized bone replacement. Computer-aided design (CAD) provides a practical and exacting method of customizing replacement scaffolds, to produce a perfect fit for each individual defect. Two major advantages of this technique are the production of an optimal three-dimensional aesthetic outcome and the prevention of creating a secondary skeletal defect. It should be emphasized that the endocultivation technique is still very new, and such prefabricated flaps are currently indicated only for patients who have poor potential skeletal donor sites.

ANATOMY

The latissimus dorsi is a flat, fanlike muscle that arises directly from the spinal processes of the lower six thoracic vertebrae, the lumbar and sacral vertebrae, and the dorsal iliac crest via the thoracolumbar fascia. The muscle inserts between the teres and pectoralis muscles at the humerus, and together with the teres major, it forms the posterior axillary fold (7). The main nutrient vessel is the thoracodorsal artery, which regularly gives off a strong branch to the serratus anterior muscle. The length of the extramuscular part of the vessel course varies from 6 to 16 cm and is about 9 cm, on average (8). The extramuscular part gives off several minor branches (7). At the point of origin from the subscapularis vessels, the thoracodorsal vessels have diameters of 1.5 to 4 mm (artery) and 3 to 5 mm (vein after unification of the two concomitant veins) (7, 8). Whereas the thoracodorsal artery provides blood mainly to the proximal and lateral two-thirds of the muscle, the distal parts of the muscle are reached by perforating branches of the intercostal arteries (7, 8).

Only gold members can continue reading. Log In or Register to continue