Abstract
Bone tissue regeneration in critical-size defects is possible after implantation of a 3D scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing. Sodium alendronate (Aln), a widely used anti-osteoporosis drug, exhibits strong inhibitory effect on bone resorption performed by osteoclasts. Thus, we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide scaffolds and poly(l-lactide-co-glycolide) microparticles (MPs) loaded with Aln. The MPs were effectively attached to the surface of the scaffolds’ pore walls by human recombinant collagen. Drug release from the scaffolds was characterized by initial burst (24 ± 6% of the drug released within first 24 h) followed by a sustained release phase (on average 5 µg of Aln released per day from Day 3 to Day 18). In vitro tests evidenced that Aln at concentrations of 5 and 2.5 µg/ml was not cytotoxic for MG-63 osteoblast-like cells (viability between 81 ± 6% and 98 ± 3% of control), but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells, as shown by reduced fusion capability and decreased tartrate-resistant acid phosphatase 5b activity (56 ± 5% reduction in comparison to control after 8 days of culture). Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis, reducing osteoclast activity, but not affecting osteoblast functions, which may be beneficial in the treatment of critical-size bone tissue defects.
Highlights
Bone tissue has the intrinsic capacity for regeneration, extensive bone defects originating from illnesses, tumour resection, trauma or bacterial infections do not heal without intervention [1]
Such highly porous TiO2 scaffolds implanted in extraction sockets of minipigs jaws provided adequate support for bone regeneration and after 6 weeks of healing newly formed bone tissue was found in the whole volume of the implanted scaffolds [15]
Aln-loaded MPs were immobilized on the scaffolds surface with the use of collagen solution (40 mg/ml) in such a way that calculated amount of Aln per scaffold was 200 mg
Summary
Bone tissue has the intrinsic capacity for regeneration, extensive bone defects originating from illnesses, tumour resection, trauma or bacterial infections do not heal without intervention [1]. Ceramic materials (e.g. hydroxyapatite, tricalcium phosphate or bioactive glasses) gain particular interest in this application due to their chemical and structural similarity to the native bone [3, 8,9,10] Their poor mechanical properties (compressive strength lower than 2 MPa [11]) compared with those of bone have hindered their clinical applications; as a result they are practically used in the non-load-bearing sites [12, 13]. It was already evidenced that the TiO2 scaffolds with porosity over 90% and compressive strength of 3.4 MPa (similar to the strength of healthy trabecular bone, i.e. 2–12 MPa) were biocompatible and enhanced tissue regeneration in vivo [14, 17,18,19,20]. Such highly porous TiO2 scaffolds implanted in extraction sockets of minipigs jaws provided adequate support for bone regeneration and after 6 weeks of healing newly formed bone tissue was found in the whole volume of the implanted scaffolds [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
