So far, how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic. In this study, a strategy of combining osteoinductive biphasic calcium phosphate (BCP) bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects (3.0 cm in length) in goat femur model. The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa, and total porosity of 84%. The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage, promoting the osteogenic process both guided and induced by the BCP scaffolds. At 9 months postoperatively, good integration between the implants and host bone was observed, and a large amount of newborn bones formed, accompanying with the degradation of the material. At 18 months postoperatively, almost the complete new bone substitution in the defect area was achieved. The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery. Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects. The current study could provide an effective method to treat the clinical large segmental bone defects.

The surface microstructures of calcium phosphate ceramics play an essential role in determining bone regeneration. However, it is difficult to produce micro/nano-structures on the surface of the porous hydroxyapatite (HA) scaffolds. In this study, we successfully developed and fabricated various micro/nano-structured surfaces on the HA scaffolds in copper ion (Cu²⁺)-containing solutions under hydrothermal conditions. The micro/nano-structures on the surface of the HA scaffolds were controlled by modulating the Cu²⁺ concentrations during the hydrothermal process. With an increase in the Cu²⁺ concentration, the surface morphology of the HA scaffolds changed significantly from sphere-like to flower-like, before becoming nano-structures. These findings indicated that the Cu²⁺ concentration affects the morphologies of calcium phosphate coatings that grow on the HA scaffolds. In vitro endothelial cell (EC) cultures showed that the cell proliferation was significantly enhanced when cultured on the flower-like morphology compared with other morphologies. Furthermore, an in vivo test in New Zealand rabbits demonstrated that the HA scaffold with the flower-like surface resulted in more angiogenesis compared with the control scaffold. This copper-assisted hydrothermal deposition process provides a simple and controllable route for engineering a micro/nano-structured surface on the HA scaffolds, which has benefits in terms of angiogenesis and bone regeneration.

The lack of vascular tissue and the low metabolism and biological activity of mature chondrocytes lead to the low regeneration ability of articular cartilage. People try to solve this problem through various methods, but the effect is not very ideal. Inspired by the piezoelectric effect of collagen in cartilage tissue, this work focused on the design of a biomimetic hydrogel by introducing piezoelectric materials and silver nanowires into hydrogel to endow them with piezoelectric and antibacterial properties to promote tissue regeneration. Additionally, the mechanical and swelling properties of the material were adjusted to match natural articular cartilage. Based on bionic principles, a double-layer piezoelectric hydrogel was prepared and applied for the repair of osteochondral defects. An enhanced repair effect of osteochondral defects has been seen, which has demonstrated potential values for future application in bionics principle- and piezoelectric effect-based osteochondral tissue engineering. Furthermore, piezoelectric effect-induced degradation was observed. These results fully indicated the positive effect of the piezoelectric effect on promoting the regeneration of osteochondral tissue and in vivo degradation of materials.

The bone defects caused by trauma and disease have become a major difficulty in the treatment of clinical bone defects, and bone tissue engineering has become a promising treatment strategy. It was found that mechanical stimulation regulated the development of bone constructs by affecting the distribution and differentiation of cells on them. In this study, tissue-engineered bone grafts with enhanced bioactivity and self-adaptability were constructed by BMSCs and biphasic calcium phosphate (BCP) scaffolds under periodic micro-vibration stimulation (MVS) with a frequency of 40 Hz and a magnitude of 0.3 g. The results of the material characterization indicated that the BCP scaffolds created a more favourable osteogenic micro-environment with promoted calcium ion release, protein adsorption and mineralization deposition under the micro-vibration stimulation. The in vitro results showed that the apoptosis of BMSCs increased significantly on day 1, but from day 3 on, the proliferation increased and apoptosis decreased. Cells were evenly distributed on the scaffolds, exhibiting tight adhesion in a flat-shape and distinct matrix mineralization. F-actin and ALP expression significantly increased and meanwhile osteogenesis-related genes including Runx2, Col-I, ALP, and OCN were significantly up-regulated. Western blotting results suggested that the ERK1/2 and Wnt/β-catenin signalling pathways were involved in the osteogenic behaviour of BMSCs induced by MVS. In vivo experiments showed that grafts had stronger osteoinduction and mechanical adaptability. Taken together, this study suggested that micro-vibration stimulation combined with BCP scaffolds with good osteoinduction could be a promising approach for constructing tissue engineered bone grafts with enhanced bioactivity, mechanical adaptability, and bone regeneration repair capability.

Macroporous characteristics have been shown to play a key role in the osteoinductivity of hydroxyapatite ceramics, but the physics underlying the new bone formation and distribution in such scaffolds still remain elusive. The work here has emphasized the osteoinductive capacity of porous hydroxyapatite scaffolds containing different macroporous sizes (200–400 μm, 1200–1500 μm) and geometries (star shape, spherical shape). The assumption is that both the size and shape of a macropore structure may affect the microfluidic pathways in the scaffolds, which results in the different bone formations and distribution. Herein, a mathematical model and an animal experiment were proposed to support this hypothesis. The results showed that the porous scaffolds with the spherical macropores and large pore sizes (1200–1500 μm) had higher new bone production and more uniform new bone distribution than others. A finite element analysis suggested that the macropore shape affected the distribution of the medium–high velocity flow field, while the macropore size effected microfluid speed and the value of the shear stress in the scaffolds. Additionally, the result of scaffolds implanted into the dorsal muscle having a higher new bone mass than the abdominal cavity suggested that the mechanical load of the host tissue could play a key role in the microfluidic pathway mechanism. All these findings suggested that the osteoinduction of these scaffolds depends on both the microfluid velocity and shear stress generated by the macropore size and shape. This study, therefore, provides new insights into the inherent osteoinductive mechanisms of bioceramics, and may offer clues toward a rational design of bioceramic scaffolds with improved osteoinductivity.