In vivo evaluation of additively manufactured multi-layered scaffold for the repair of large osteochondral defects.

The repair of osteochondral defects is one of the major clinical challenges in orthopaedics. Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects. However, less success has been achieved for the regeneration of large defects, which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue. In this study, we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques. The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen "sandwich" composite system. The microstructure and mechanical properties of the scaffold were examined, and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model. The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen-HAp scaffold, and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage, as demonstrated by hyaline-like cartilage formation. The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group. Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group. The findings showed the safety and efficacy of the cell-free "translation-ready" osteochondral scaffold, which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects. Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-021-00177-w.

Clinical Efficacy of Polycaprolactone ß-Calcium Triphosphate Composite for Osteoconduction in Rabbit Bone Defect Model.

The combination of ß-tricalcium phosphate (ß-TCP) with polycaprolactone (PCL) has been considered a promising strategy for designing scaffolds for bone grafting. This study incorporated PCL with commercially available ß-TCP (OsteoceraTM) to fabricate an injectable bone substitute and evaluate the effect of PCL on compressive strength and setting time of the hydraulic cement. The mechanical testing was compliant with the ASTM D695 and ASTM C191-13 standards. Results showed that PCL-TCP composite presented a well-defined architecture with uniform pore distribution and a significant increase in compressive strength compared with ß-TCP alone. Eighteen rabbits, each with two surgically created bone defects, were treated using the PCL-TCP composites. The composite materials were resorbed and replaced by newly formed bone tissue. Both PCL-TCP and ß-TCP demonstrated equivalent clinical effects on osteoconduction property in terms of the percentage of newly formed bone area measured by histomorphometric analysis. PCL-TCP was proven to be as effective as the commercially available ß-TCP scaffold (OsteoceraTM).

Determination of an Initial Stage of the Bone Tissue Ingrowth Into Titanium Matrix by Cell Adhesion Model.

For achieving early intervention treatment to help patients delay or avoid joint replacement surgery, a personalized scaffold should be designed coupling the effects of mechanical, fluid mechanical, chemical, and biological factors on tissue regeneration, which results in time- and cost-consuming trial-and-error analyses to investigate the in vivo test and related experimental tests. To optimize the fluid mechanical and material properties to predict osteogenesis and cartilage regeneration for the in vivo and clinical trial, a simulation approach is developed for scaffold design, which is composed of a volume of a fluid model for simulating the bone marrow filling process of the bone marrow and air, as well as a discrete phase model and a cell impingement model for tracking cell movement during bone marrow fillings. The bone marrow is treated as a non-Newtonian fluid, rather than a Newtonian fluid, because of its viscoelastic property. The simulation results indicated that the biofunctional bionic scaffold with a dense layer to prevent the bone marrow flow to the cartilage layer and synovia to flow into the trabecular bone area guarantee good osteogenesis and cartilage regeneration, which leads to high-accuracy in vivo tests in sheep . This approach not only predicts the final bioperformance of the scaffold but also could optimize the scaffold structure and materials by their biochemical, biological, and biomechanical properties.