Hydroxyapatite (HAP), as a common bone repair material, still faces the risk of bacterial infection in the treatment of infectious bone defects, whose limited osteogenic properties also hinders its further application. This study used a coprecipitation method to prepare the manganese doped hydroxyapatite nanorod (MnHAP), which exhibited excellent cell biocompatibility, high antibacterial efficiency and osteogenic properties. Antibacterial experiments showed that the inhibition rates of MnHAP10(n(Mn)/n(Ca+Mn)=10%)) against Escherichia coli and Staphylococcus aureus can reach 77.85% and 75.92%, respectively. Moreover, the antibacterial efficiency of MnHAP10 against Escherichia coli can be further enhanced (97.63%) under 808 nm near-infrared light irradiation. Cell proliferation and related osteogenic gene experiments display that MnHAP is beneficial for the proliferation and differentiation of osteoblasts, which improves protein adsorption capacity, stimulates osteogenic activity, and promotes the expression of related osteogenic genes, demonstrating its good biocompatibility. Therefore, MnHAP nanorods are expected to provide a new approach in the treatment of infectious bone defects.

The question of what qualities excellent medical bioceramics must possess to ensure satisfactory prognosis for bone healing and reconstruction remains a topic of great interest in both clinical and biomaterial sciences. Our team has been dedicated to researching medical bioceramics since the 1990s, involving basic scientific research, applied translational research, and clinical trials. Consequently, we have amassed a wealth of research and implementation experience. In this article, we aim to explore the subject of “Functional Bioadaptability in Medical Bioceramics”, specifically focusing on calcium phosphate-based materials. We summarized how to effectively combine bioadaptability with design and manufacturing of medical bioceramics in the background of orthopedic clinical application, with the following aspects of structural adaptability, degradative adaptability, mechanical adaptability, and application adaptability. Hopefully, some suggestions put forward can ultimately provide valuable insights and recommendations for the design, production, supervision, and application of the upcoming medical bioceramics.

Archaeological weathered bones are usually porous and fragile, easily to warp, crack and crumble. To avoid these relic damages, consolidation technology is badly needed. Here, we explored a new consolidation method for weak bone relics using hydroxyapatite as protectant. Briefly, dispersion of calcium oxide mixed with calcium hydrophosphate in alcohol was used firstly to permeate into the fragile bones as precursor of hydroxyapatite consolidant. Then pure water was used to trigger the reaction between calcium oxide and calcium hydrophosphate, which leads to formation of a continuous phase of hydroxyapatite consolidant. By filling and bridging the pores or fissure inside the fragile bones, hydroxyapatite consolidant can act as a reinforcement material. Effects of the mass ratio of calcium oxide to calcium hydrophosphate (1 : 1, 1 : 3, 1 : 4, 1 : 5, 1 : 6, 1 : 7) and the application ways (brushing, drip infiltration and soaking) on the protective performance were investigated by scanning electron microscope (SEM), energy dispersive spectroscope (EDS), X-ray diffraction (XRD) and characterizations of color difference, weight increment, porosity, density and cohesive strength determination. The results showed that the best consolidation performance could be obtained when the mass ratio of 1 : 3 and the brushing consolidation method were adopted. In this case, porosity of the fragile bones decreased by 17.3%. Mass, density and cohesive strength of the fragile bones increased by 38.39%, 34.49% and 16.32%, respectively. Moreover, the color difference of bones is less than 3.0, which is allowable in the field of heritage conservation.

Titanium and its alloys have been widely used as hard tissue implants due to their excellent mechanical properties and biocompatibilities. However, the lack of biological activity on its surface and the inflammatory reaction after implantation can easily lead to unsatisfactory osseointegration. In this work, the wettability of titanium oxide coatings was modulated by annealing in different atmospheres, and the effects of surface wettability on polarization of macrophages and osteogenic differentiation of mBMSCs were studied. The results showed that, compared to the hydrophilic titanium oxide coating (~10º, PEO-A), the titanium oxide coating with contact angle about 90º (PEO-A-V) inhibited the polarization of macrophages towards M1 pro-inflammatory direction under the mono-culture condition. However, under the co-culture condition, the titanium oxide coating with contact angle about 90º promoted macrophage polarization towards M2 and significantly upregulated gene expressions of osteogenic markers related to mBMSCs, indicating better immunomodulatory effects on osteogenic differentiation of mBMSCs.

Pulp capping agents are effective materials which can preserve dental pulp and treat caries in different ways. It is urgently demanded to establish a guidance to select the appropriate pulp capping agents according to the conditions of pulp and cary requirements. In this work, morphology, composition, physical, and chemical properties of three commonly used clinical pulp capping agents, namely dental zinc oxide eugenol cement (ZnO), self-curing calcium hydroxide (Dycal), and light-curing calcium hydroxide (Calcimol), were studied. Their antibacterial, cytocompatibility and blood compatibility were evaluated. The results showed that ZnO was hydrophobic and its effective component, crystallized ZnO, could consistently release zinc ions, giving its alkaline environment to inhibit bacteria. Structure, morphology and components in Dycal were similar to those in Calcimol. However, its surface was more hydrophobic and its release amount of calcium ions was larger than that of Calcimol. It formed an alkaline micro-environment, thereby possessed good antibacterial ability and biocompatibility. Meanwhile, Calcimol was hydrophilic and convenient to operate, and released less metal ions. Due to its safe composition, Calciomol exhibited excellent biocompatibility but slightly weaker antibacterial property. Our results suggested that these comparative results might be a useful clinical guidance for selecting appropriate pulp capping agents according to the degree of caries and the health status of dental pulp to treat the caries.

Titanium orthopaedic implants present a risk of infection and require the development of antibacterial, but still biocompatible and non-resistant coatings. Magnesium oxide (MgO) coatings were prepared on micro-arc oxidized titanium by electrophoretic deposition for 15, 30, 45, or 60 s. Nano-sized MgO particles agglomerated to form homogeneous coatings with surface coverage increasing with the duration of deposition. The four groups produced antibacterial rates of 1%, 69%, 83%, and 84% after co-cultured with S. aureus for 6 h, and 81%, 86%, 89%, and 98% after co-cultured for 24 h. Electron and fluorescence microscopies showed decreasing density of bacterial cells and proportion of living cells with increasing time of deposition. Mouse osteoblasts seeded on the four groups had survival rates of 108%, 89%, 53%, and 27% on day 1, and 139%, 117%, 112%, and 66% on day 5. Proportion of dead cells on the coated samples increased with increasing time of deposition but less than 5% on day 5. These results indicate that MgO coatings prepared by electrophoretic deposition for 30 s is reasonable in vitro antibacterial activities and cytocompatibility.

Beta tricalcium phosphate (β-TCP) ceramic substituted materials have attracted a large amount of attention in the last decades because of their chemical similarity with bone inorganic components, good biocompatibility, and osteoconductivity. Such materials can be used for bone replacement and bone formation in various forms, such as nanoparticles, scaffolds and microspheres. In this study, five different microsphere materials of tricalcium phosphate/trimagnesium phosphate (TMP) (TCP, 25% TMP, 50% TMP, 75% TMP, and TMP) composites were prepared and characterized. With the increase of TMP content in the composite microspheres, the cumulative concentration of Mg²⁺ and Ca²⁺ released from the microspheres increased, indicating that TMP can regulate the degradation rate of the composite microspheres. The osteoblast precursor cell line (MC3T3-E1 cells) and human umbilical vein endothelial cells (HUVECs) were used as models to evaluate the biocompatibility, angiogenesis and osteogenesis of the composite microspheres. The results showed that compared with TCP, TMP and 75% TMP group, 25% TMP and 50% TMP composite microspheres had better cell compatibility and had a certain proliferative effect on HUVECs. Therefore, composite microspheres of 25% TMP and 50% TMP have more significant positive effects on angiogenesis and osteogenesis.

Natural bone has a unique micro-/nano-structure, which is composed of organic nanomaterials (collagen fibers) and inorganic nanomaterials (hydroxyapatite). Thus, compared with traditional synthetic materials, natural bone has incomparable advantages in biological, functional and mechanical properties. In the research of tissue engineering and regenerative medicine, biomaterial scaffold with micro-/nano-structures simulating the characteristics of natural bone tissue are one of the research focuses. In recent years, researchers have found that micro-/nano-structured biomaterials can effectively regulate cell proliferation, differentiation and migration, and have a strong ability to promote cell osteogenic differentiation, so as to promote bone tissue regeneration in vivo. In this article, we focus on reviewing recent research progress of biomaterial design on simulating the hierarchical characteristics of natural bone, analyzing the complicated interaction between micro-/nano-structured biomaterials and cells, and summarizing their applications in bone tissue engineering to provide new ideas for the design of biomaterials.

Bioceramic scaffolds with excellent osteogenesis ability and degradation rate exhibit great potential in bone tissue engineering. Akermanite (Ca₂MgSi₂O₇) has attracted much attention due to its good mechanical property, biodegradability and enhanced bone repair ability. Here, akermanite (Ca₂MgSi₂O₇) scaffolds were fabricated by an extrusion-type 3D printing at room temperature and sintering under an inert atmosphere using printing slurry composed of a silicon resin as polymer precursor, and CaCO₃ and MgO as active fillers. Furthermore, the differences in structure, compressive strength, in vitro degradation, and biological properties among akermanite, larnite (Ca₂SiO₄) and forsterite (Mg₂SiO₄) scaffolds were investigated. The results showed that the akermanite scaffold is similar to those of larnite and forsterite in 3D porous structure, and its compressive strength and degradation rate were between those of the larnite and forsterite scaffolds, but it showed a greater ability to stimulate osteogenic gene expression of rabbit bone marrow mesenchymal stem cells (rBMSCs) than both larnite and forsterite scaffolds. Hence, such 3D printed akermanite scaffold possesses great potential for bone tissue engineering.

Borosilicate bioglass has attracted extensive attention due to its stable structure and excellent biological activity. However, the rate of its mineralization process is fast in the initial stage and slow in the middle and late stages, which limits the application of borosilicate bioglass. As an auxiliary method, the near-infrared (NIR) laser can accelerate the degradation of bioglass. Therefore, we prepared a core-shell borosilicate bioglass with titanium nitride as the core and bioglass (40SiO₂-20B₂O₃-36CaO-4P₂O₅) as the shell, and used near-infrared laser regulation technology to intervene the mineralization process of the composite bioglass. The experimental results show that the core-shell bioglass exhibits a significant photothermal effect, and the photothermal ability increases with the increases of the doping amount of TiN NPs and the laser power density. During the in vitro immersion, near-infrared laser increased the degradation rate of bioglass. After immersion for 7 d, the contents of calcium and boron in the SBF are increased by 12%-16% and 8%-11%, respectively. Meanwhile, the formation efficiency of hydroxyapatite is significantly improved. Cell proliferation activity test shows that the sample has good biological safety. Therefore, near-infrared light can accelerate the degradation and mineralization of functional core-shell bioactive glass, which is expected to play a regulatory role.

As a common malignant bone tumor, osteosarcoma is usually treated by surgical resection. However, the bone defects caused by surgery are difficult to heal, and the possibility of osteosarcoma recurrence can also be increased by the residual tumor cells. Therefore, a Nd-doped mesoporous borosilicate bioactive glass-ceramic bone cement was developed for repair of bone defects and synergistic therapy of osteosarcoma. Firstly, as photothermal agent and drug carrier, Nd-doped mesoporous borosilicate bioactive glass-ceramic (MBGC-xNd) microspheres were prepared through Sol-Gel method and solid-state reaction. Then MBGC-xNd microspheres were mixed with sodium alginate (SA) solution to prepare injectable bone cement (MBGC-xNd/SA). The results showed that Nd³⁺ endows microspheres with controllable photothermal properties, and microspheres loaded with doxorubicin (DOX) showed sustained drug release behavior. In addition, the drug release from drug-loaded bone cement was significantly accelerated with the increase of temperature, indicating that the heat generated by photothermal therapy had the possibility of promoting the release of DOX. In vitro cell experiment results showed that MBGC-xNd/SA had good osteogenic activity. Simultaneously, photothermal-chemical combination therapy had a more significant killing effect on MG-63 osteosarcoma cells, indicating a synergistic effect. Therefore, MBGC-xNd/SA, as a novel multifunctional bone repair material, exhibits a potential application in the postoperative treatment of osteosarcoma.

Orthopedic surgery and postoperative inflammation are easy to induce oxidative stress, which hinders the process of bone repair. Bioactive ceramics have excellent osteogenic properties, but lack the ability to resist oxidative stress. Therefore, it is of great significance to develop a bioactive ceramic material with antioxidant function. Here, cobalt-incorporated chloroapatite (Co-MS-TCP) was prepared by a molten salt method, in which the mixture of lithium chloride and potassium chloride was used as a molten salt system, and β-phase tricalcium phosphate (TCP) and cobalt chloride hexahydrate (CoCl₂∙6H₂O) were used as raw material and cobalt source, respectively. The antioxidant ability of Co-MS-TCP was determined by catalyzing H₂O₂ clearance. The cytocompatibility and anti-oxidation of Co-MS-TCP were further evaluated by analyzing the changes of cell viability and intracellular reactive oxygen species (ROS). Results showed that Co-MS-TCP with controllable cobalt content can be prepared by a molten salt method with changing the addition amount of CoCl₂∙6H₂O source. The scavenging capacity of H₂O₂ increased with the increase of cobalt content in chlorapatite, and more than 90% of H₂O₂ could be scavenged within 6 h due to the catalytic activity of Co-MS-TCP. Furthermore, cell experiments confirmed the cytocompatibility and antioxidative property of Co-MS-TCP. 3% Co-MS-TCP at a concentration of 1.5 mg·mL^-1 could still ensure the survival rate of bone marrow mesenchymal stem cells and chondrocytes to be higher than 85%, and 3% Co-MS-TCP can also significantly reduce the content of intracellular ROS for the H₂O₂-stimulated cells. Therefore, molten salt method is an effective way to prepare cobalt-incorporated bioactive ceramics with antioxidative property, which also provides a promising strategy for the development of functional bioactive ceramics with high catalytic activity and biocompatibility.

β-tricalcium phosphate (β-TCP) has biodegradability and biocompatibility, but its inherent brittleness limits its application in load-bearing implants. In order to further improve the mechanical property and biocompatibility of β-TCP, β-TCP/NC (TNC) composite scaffold with nano clay (NC) as additive and the porous structure of the scaffold has a pore size of 200-300 μm was prepared by digital light processing (DLP) technique. When the content of NC is 10% (in mass), the sintering shrinkage of each structural feature of the support (TNC10) is the smallest. Addition of NC does not change the phase composition of TCP, and Si and Mg elements are evenly distributed on the surface of the scaffold. Addition of NC can improve the compression strength of TCP scaffolds. NC (particle size < 500 nm) is fused in the gap of TCP particles. Compared with pure TCP scaffolds, the compression strength of TNC10 is increased by 10%. In addition, the specific surface area of TNC10 group was more than 2 times higher than that of pure TCP. TNC degradation rate is faster while Ca²⁺, Mg²⁺, Si⁴⁺, and Li²⁺ can be continuously released, which maintains a weakly alkaline environment. The results demonstrate that the addition of NC has a certain promotion effect on the mechanical strength, degradation performance β-TCP scaffolds. Porous bioceramic scaffolds with good physical, chemical property by DLP method have great application prospects in the field of bone repair.

Mesoporous silica particles have characteristics of excellent chemical stability, large specific surface area and convenient surface modification, showing promising application in drug carriers. However, their lack of bioactivity and slow biodegradation rate limit this application. To overcome these shortcomings, creating suitable biomaterials for drug carriers has become an indispensable and, therefore, important research direction in materials science. Compared with pure silica or silicate glasses, borosilicate glasses with excellent bioactivity degrade faster, enabling them suitable and favorable for drug carriers. Here, we synthesized mesoporous borosilicate glass microspheres (MBGMs) and characterized their properties of loading and releasing an antitumor drug, doxorubicin hydrochloride (DOX), and releasing their own various ions triggered by degradation. The results showed that BMGMs had a DOX loading amount of about 25 mg/g. Introduction of boron improved chemical activity and degrading rate of MBGMs, resulting in more DOX released in acidic enviroment than alkaline condition, which displayed a certain acid-responsive drug releasing behavior. Meanwhile, MBGMs can release functional ions such as SiO₄^4-, BO₃^3- and Ca²⁺, and induce hydroxyapatite formation, indicating sustained ion releasing ability and excellent bioactivity. Altogether, MBGMs, as a novel kind of drug carrier, have a potential application in the field of pathological bone defect repairing.

Electrical signals generated by piezoelectric materials can promote proliferation and differentiation of osteoblasts, but they can’t induce mineralization, while bioactive materials can induce the deposition of bone like hydroxyapatite in physiological environment, but can not generate electrical signal to promote osteogenesis. Therefore, it is of great significance to develop a composite bioactive piezoelectric material that can not only generate electrical signals, but also induce mineralization and deposition. Here, we used barium titanate as piezoelectric component and calcium silicate as bioactive component to prepare barium titanate/calcium silicate composite as bioactive/piezoelectric ceramics by solid-state sintering method. Piezoelectric properties of the ceramics were tested, and the ability of inducing mineralization was evaluated by in vitro mineralization experiment. The experimental results show that when the content of calcium silicate reaches 30%, the composite ceramics still have certain piezoelectric property (d₃₃=4 pC·N^-1), and can induce the deposition of calcium phosphate in simulated body fluid. Therefore, the combination of barium titanate and calcium silicate can synchronously afford piezoelectric and biological activities, which provides a new choice for bone repair materials.

Inflammation in bone defect after being implanted scaffold is related to oxidative stress, which is caused mainly by higher concentration of hydrogen peroxide (H₂O₂). Manganese dioxide (MnO₂) can catalyze H₂O₂ decomposition to decrease excessive H₂O₂ in the surrounding environment of scaffolds. Furthermore, the oxygen (O₂) generated by the decomposition of H₂O₂ can alleviate the hypoxia caused by insufficient blood supply in bone defects, which is conducive to bone tissue regeneration. Here, a simple redox method was proposed to deposit MnO₂ particles on the surface of 3D printed bioactive glass (BG) scaffolds for the preparation of BG-MnO₂ composite scaffolds (BGM), which endows BG-MnO₂ scaffolds with the ability of H₂O₂ scavenging and O₂ supplying simultaneously. The results showed that the MnO₂ content deposited on the surface of BGM scaffolds was increased with the increase of potassium permanganate concentration in the reaction solution, and the compressive strength of BGM scaffolds was increased with the increase of MnO₂ content. However, porosity and degradation rate of these scaffolds with or without MnO₂ remained the same. More importantly, BGM scaffolds can continuously catalyze the decomposition of H₂O₂ to produce O₂ in H₂O₂ environment. When BGM with different Mn content scaffolds (BMG5 and BGM9) catalyzed the decomposition of H₂O₂ to produce O₂ in 2 mmol/L H₂O₂ solution, the saturated oxygen concentration in the solution could reach 8.4 and 11 mg/L, respectively. In vitro cell experiments showed that BGM scaffolds could promote the proliferation and alkaline phosphatase activity of rabbit bone marrow mesenchymal stem cells. Hence, BGM scaffolds show great potential in bone regeneration.