Intrinsic Osteoinduction of Biomimetic Nanostructured Calcium Phosphate Scaffolds for the Treatment of Critical-Sized Bone Defects
Introduction
Most commercial calcium phosphate bone substitutes are obtained by sintering (CaP-sin) at high temperatures (1000°C), which results in absence of nanostructure and low specific surface area (SSA=1 m2/g), thus limiting the intrinsic osteoinductive potential of biomaterials. Our group has developed biomimetic bone substitutes (CaP-bio), based on a dissolution-precipitation reaction at physiological temperature (37°C), obtaining biomaterials with similar composition to bone mineral phase (calcium-deficient hydroxyapatite), controlled nanoporosity and high SSA (40 m2/g), which is expected to have a positive impact on the intrinsic osteoinductive activity.
Objective
To evaluate the intrinsic osteoinductive capacity of biomimetic CaP-based biomaterials with tailored nanoporosity.
Methods
Two different strategies were used to fabricate scaffolds with different architectures: i) Foaming (concave macropores, CaP-Foam); ii) 3D-printing (prismatic macropores). A CaP-sin-Foam, beta-tricalcium phosphate (beta-TCP) was used as control. The in vivo study was carried out in a standardized model of intramuscular implantation (6/12 weeks) in beagle dog (n=6). A qualitative analysis assessing the presence of newly formed ectopic bone within the macropores of biomaterials by means of backscattered scanning electron microscopy and microscopic computed tomography was performed.
Results
New ectopic lamellar bone formation was only observed in CaP-bio-Foam group (4/6 animals) at 6 weeks and in CaP-bio-Foam (6/6 animals) and beta-TCP (1/6 animals) groups at 12 weeks. No ectopic bone formation was found in 3D-printed scaffolds.
Conclusions
Nanostructured CaP-bio scaffolds with concave macropores and high SSA possess a higher osteoinductive potential than CaP-sin, which has an extraordinary clinical relevance for the treatment of large bone defects in small animal veterinary surgery.