Malignant bone tumor is one of the major bone diseases. The treatment of such a bone disease typically requires the removal of bone tumor and regeneration of tumor-initiated bone defects simultaneously. To address this issue, it is required that implanted biomaterials should combine the bifunctions of both therapy and regeneration. In this work, a bifunctional graphene oxide (GO)-modified β-tricalcium phosphate (GO-TCP) composite scaffold combining a high photothermal effect with significantly improved bone-forming ability is prepared by 3D-printing and surface-modification strategies. The prepared GO-TCP scaffolds exhibit excellent photothermal effects under the irradiation of 808 nm near infrared laser (NIR) even at an ultralow power density of 0.36 W cm⁻², while no photothermal effects are observed for pure β-TCP scaffolds. The photothermal temperature of GO-TCP scaffolds can be effectively modulated in the range of 40–90 °C by controlling the used GO concentrations, surface-modification times, and power densities of NIR. The distinct photothermal effect of GO-TCP scaffolds induces more than 90% of cell death for osteosarcoma cells (MG-63) in vitro, and further effectively inhibits tumor growth in mice. Meanwhile, the prepared GO-TCP scaffolds possess the improved capability to stimulate the osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) by upregulating bone-related gene expression, and significantly promote new bone formation in the bone defects of rabbits as compared to pure β-TCP scaffolds. These results successfully demonstrate that the prepared GO-TCP scaffolds have bifunctional properties of photothermal therapy and bone regeneration, which is believed to pave the way to design and fabricate novel implanting biomaterials in combination of therapy and regeneration functions.

Because cartilage and bone tissues have different lineage-specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium-containing mesoporous bioglass (Li-MBG) scaffold is developed. The efficacy and mechanism of Li-MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro-CT results show that Li-MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage-like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li-MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi-lineage conducive scaffolds that enhance regeneration of osteochondral defects.

Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the β-tricalcium phosphate (β-TCP) stimulated osteogenesis. It was found that osteocytes responded to the β-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of β-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the biological properties of biomaterials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2813–2823, 2014.

The goal of periodontal tissue engineering is to regenerate alveolar bone, root cementum and periodontal ligament. To achieve this goal, bioactive scaffolds play an important role in inducing in vitro osteogenic/cementogenic gene expression of periodontal ligament cells (PDLCs) and in vivo bone/cementum formation. Diopside (DIOP: CaMgSi₂O₆) ceramics have shown excellent in vitro bioactivity for potential bone repair application. However, there is no study about DIOP porous scaffolds for periodontal tissue engineering. The aim of this study is to prepare DIOP scaffolds and investigate their in vitro and in vivo osteogenesis/cementogenesis for periodontal regeneration application. DIOP scaffolds with highly porous architecture were prepared and β-tricalcium phosphate (β-TCP) scaffolds were used for the control. The interaction of DIOP scaffolds with PDLCs was studied by investigating cell attachment, proliferation and ostegenic/cementogenic differentiation of PDLCs. DIOP scaffolds were implanted into the periodontal defects of beagle dogs to evaluate their in vivo osteogenesis/cementogenesis by hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase staining, and immunohistochemistry (type I collagen: Col I; cementum attachment protein) analyses. The results have shown that DIOP scaffolds supported the attachment and proliferation of PDLCs. DIOP scaffolds significantly enhanced osteogenesis/cementogenesis-related gene expression (Col 1, Runx2, transforming growth factor beta 1, and bone morphogenetic protein 2) of PDLCs, compared to β-TCP scaffolds. The in vivo study showed that DIOP scaffolds induced new bone and cementum regeneration of periodontal tissue defects. The rate of new bone and cementum in DIOP scaffolds is comparable to that in conventional β-TCP scaffolds. Our results indicated that silicate-based DIOP ceramics could not only be used for bone tissue engineering, but also for periodontal tissue engineering due to their excellent in vitro and in vivo osteogeneis/cementogenesis. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 105–116, 2014.

Polyethylene terephthalate (PET) artificial ligament has been widely used for treating serious cases of anterior cruciate ligament (ACL) injuries. However, the major drawback of PET artificial ligament is their insufficient surface bioactivity which hinders its osseointegration and mechanical anchorage in the bone tunnel. The aim of the present study is to prepare functional akermanite (AKT) nanocoatings on PET artificial ligaments by pulsed laser deposition (PLD) in order to promote the in vitro osteogenic differentiation of BMSCs and in vivo osteointegration. The results show that AKT glass nanocoatings on PET with uniform nanoparticles (around 30 nm) have been successfully prepared by PLD method. The in vitro study displays that the prepared AKT-PET grafts support the attachment of BMSCs, and significantly stimulate the proliferation and osteogenic differentiation of BMSCs in comparison to pure PET grafts. AKT coatings on PET grafts promote the regeneration of new bone at the interface of the grafts and host bone tissues, and enhance the bonding strength in vivo as compared to pure PET grafts. The study establishes a viable method to apply PLD technique for preparing bioactive ceramic-coated PET artificial ligaments with significantly improved osseointegration for ACL reconstruction.

Nanorod-assembled FHA microspheres with different F contents were for the first time prepared through a facile one-step hydrothermal method. The effect of the reaction time and pH value of reaction solutions on the FHA morphology was investigated to elucidate the self-assembly process of FHA microspheres. The results showed pH values had significant effect on the morphology of the formed FHA crystals, which were self-assembled into sphere-like sturctures at high pH conditions and rod-like structures at low pH values. The results suggested that formation of FHA crystals with varied morphology may be directly related to Ca²⁺ release kinetics from EDTA-Ca-Na₂ at different pH conditions. Furthermore, it was found that the chemical stability of FHA microspheres was dependent on the F content in the materials, and high F contents in FHA microspheres lead to improved chemical stability. These results suggest that the prepared self-assembled FHA microspheres may be used for teeth substitution materials due to their unique hierarchical structures and controllable chemical stability.

The use of bioactive microspheres as bone filling materials has received much attention due to their ability to fill the bone defects with irregular and complex shapes and sizes. Divalent Mg²⁺ modified silicate-based diopside (DIOP: CaMgSi₂O₆) and tetravalent Zr⁴⁺ modified silicate-based baghdadite (BAGD: Ca₃ZrSi₂O₉) ceramics have shown excellent in vitro bioactivity for potential bone repair application. However, their in vivo osteogenesis has not been systematically investigated. The aim of this study is to prepare DIOP and BAGD ceramic microspheres and investigate their in vivo osteogenesis. DIOP and BAGD ceramic spheres with loose microstructure were successfully prepared. The dissolution ability of two silicate-based bioceramics was investigated by testing the release of SiO ions after soaking them in phosphate buffered saline. The ceramic spheres were implanted into supracondylar site of the femur defects in Wistar rats and the degree of in vivo osteogenesis was evaluated by hematoxylin and eosin (H and E), Safranin O staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry (type I collagen: Col I, osteopontin: OPN) analyses. The results have shown that BAGD spheres induced a higher rate of new bone formation in the defects than did DIOP and β-tricalcium phosphate (β-TCP) spheres. Immunohistochemical analysis showed greater expression of Col I and OPN in BAGD group compared to DIOP and β-TCP groups. The study indicates different ion modification playing an important role to regulate the in vivo osteogenesis of silicate-based bioceramics. BAGD spheres are a promising bone filler material due to their significantly enhanced osteogenesis, compared to β-TCP spheres. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2269–2277, 2012.