Stem Cells Associated with Macroporous Bioceramics for Long Bone Repair: 6- to 7-Year Outcome of a Pilot Clinical Study

Abstract

Extensive bone loss is still a major problem in orthopedics. A number of different therapeutic approaches have been developed and proposed, but so far none have proven to be fully satisfactory. We used a new tissue engineering approach to treat four patients with large bone diaphysis defects and poor therapeutic alternatives. 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 the ceramic cylinder seeded with cells was placed in the bone defect. Patients were evaluated at different postsurgery time intervals by conventional radiographs and computed tomography (CT) scans. In one patient, an angiographic evaluation was performed at 6.5 years follow-up. In this study we analyze the long-term outcome of these patients following therapy. No major complications occurred in the early or late 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 bone occurred 5 to 7 months after surgery. In all patients at the last follow-up (6 to 7 years postsurgery in patients 1 to 3), a good integration of the implants was maintained. No late fractures in the implant zone were observed. The present study shows the long-term durability of bone regeneration achieved by a bone engineering approach. We consider the obtained results very promising and propose the use of culture-expanded osteoprogenitor cells in conjunction with porous bioceramics as a real and significant improvement in the repair of critical-sized long bone defects.

Perfluorodecalin and bone regeneration

“…This could be the reason behind the increased soft and hard tissue formation around the implants loaded with BM compared to those without BM. Similarly to previous research, our study revealed that the combination of bioceramic implants with BM substantially increased the amount of bone growing on the outer implant surface (Kon et al, 2000;Marcacci et al, 2007). Interestingly, even though different amounts of bone grew on the outer surface of all the implants, no bone formation occurred within the inner compartment of any of the implants tested.…”

Porous scaffold architecture guides tissue formation

“…These osteoconductive scaffolds are often combined with growth factors (osteoinductive) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and/or with cells (osteogenic) (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) to induce active stimulation of bone regeneration. The objective of most of these investigations is to enable bone defect healing, which remains an unsolved clinical problem.…”

The roles of immune cells in bone healing; what we know, do not know and future perspectives

“…According to the diamond concept [12,[124][125][126][127], the biological elements of these therapies should involve MSCs and growth mediators including those promoting the new vasculature formation. Whether MSCs are delivered within concentrated or not-concentrated mononuclear bone marrow cells [128,129] or as culture-expanded pure population and loaded on matrices [130] or injected subcutaneously [131], their therapeutic use still needs further optimisation. The inflammation status could affect considerably the effectiveness of the regenerative treatments at least in part via their effect on MSCs [132].…”