Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study.

Extensive bone loss is still a major problem in orthopedics. A number of different therapeutic approacheshave been developed and proposed, but so far none have proven to be fully satisfactory. We used a newtissue engineering approach to treat four patients with large bone diaphysis defects and poor therapeuticalternatives. To obtain implantable three-dimensional (3D) living constructs, cells isolated from the patients’bone marrow stroma were expanded in culture and seeded onto porous hydroxyapatite (HA)ceramic scaffolds designed to match the bone deficit in terms of size and shape. During the surgical session,an Ilizarov apparatus or a monoaxial external fixator was positioned on the patient’s affected limb and theceramic cylinder seeded with cells was placed in the bone defect. Patients were evaluated at differentpostsurgery time intervals by conventional radiographs and computed tomography (CT) scans. In onepatient, an angiographic evaluation was performed at 6.5 years follow-up. In this study we analyze thelong-term outcome of these patients following therapy. No major complications occurred in the early orlate postoperative periods, nor were major complaints reported by the patients. No signs of pain, swelling,or infection were observed at the implantation site. Complete fusion between the implant and the host boneoccurred 5 to 7 months after surgery. In all patients at the last follow-up (6 to 7 years postsurgery inpatients 1 to 3), a good integration of the implants was maintained. No late fractures in the implant zonewere observed. The present study shows the long-term durability of bone regeneration achieved by a boneengineering approach. We consider the obtained results very promising and propose the use of cultureexpandedosteoprogenitor cells in conjunction with porous bioceramics as a real and significant improvementin the repair of critical-sized long bone defects.