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It is of significance to construct the immunomodulatory and osteogenic microenvironment for three dimension (3D) regeneration of bone tissues. 3D scaffolds, with various chemical composition, macroporous structure and surface characteristics offer a beneficial microenvironment for bone tissue regeneration. However, there is a gap between the well-ordered surface microstructure of bioceramic scaffolds and immune microenvironment for bone regeneration. In this study, a gear-inspired 3D scaffold with well-ordered surface microstructure was successfully prepared through a modified extrusion-based 3D printing strategy for immunomodulation and bone regeneration. The prepared gear-inspired scaffolds could induce M2 phenotype polarization of macrophages and further promoted osteogenic differentiation of bone mesenchymal stem cells in vitro. The subsequent in vivo study demonstrated that the gear-inspired scaffolds were able to attenuate inflammation and further promote new bone formation. The study develops a facile strategy to construct well-ordered surface microstructure which plays a key role in 3D immunomodulatory and osteogenic microenvironment for bone tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE.

To prevent postoperative skin tumor recurrence and repair skin wound, a glucose oxidase (GOx)-loaded manganese silicate hollow nanospheres (MS HNSs)-incorporated alginate hydrogel (G/MS-SA) was constructed for starvation-photothermal therapy and skin tissue regeneration. The MS HNSs showed a photothermal conversion efficiency of 38.5%, and endowed composite hydrogels with satisfactory photothermal effect. Taking advantage of the catalytic activity of Mn ions, the composite hydrogels could decompose hydrogen peroxide (H2O2) into oxygen (O2), which can alleviate the problem of tumor hypoxia microenvironment and endow GOx with an ability to consume glucose in the presence of O2 for tumor starvation. Meanwhile, hyperthermia triggered by near infrared (NIR) irradiation could not only accelerate the reaction rate of H2O2 decomposition by MS HNSs and glucose consumption by GOx, but also ablate tumor cells. The anti-tumor results showed that synergistic effect of starvation-photothermal therapy led to the highest death rate of tumor cells among all groups, and its anti-tumor effect was obviously improved as compared with that of single photothermal treatment or starvation treatment. Interestingly, the introduction of MS HNSs into hydrogels could distinctly promote the epithelialization of the wound beds by releasing Mn ions as compared with the hydrogels without MS HNSs. It is expected that such a multifunctional platform with starvation-photothermal therapy will be promising for treating tumor-caused skin defects in combination of its regeneration bioactivity in the future., Graphical abstract Schematic diagram. Schematic illustrations of (a) the fabrication of GOx-loaded MS HNSs-incorporated hydrogels (G/MS-5SA) and (b) the application of G/MS-5SA hydrogels in starvation-photothermal therapy and skin tissue regeneration.Image 1, Highlights • Glucose oxidase-loaded manganese silicate hollow nanospheres-incorporated alginate hydrogels consumed glucose in the presence of O2 for tumor starvation. • Hyperthermia could accelerate the reaction rate of H2O2 decomposition. And starvation-photothermal synergetic anti-tumor therapy effect was better than that of single treatment. • The composite hydrogels promote the epithelialization of the wound beds by releasing Mn ions.

Regeneration of osteochondral tissue is of great potentialities in repairing severe osteochondral defects. However, anisotropic physiological characteristics and tissue linage difference make the regeneration of osteochondral tissue remain a huge challenge. Herein, a multicellular system based on a bilayered co-culture scaffold mimicking osteochondral tissues was successfully developed for an alternative of osteochondral regeneration via a 3D bioprinting strategy. The dual function of integrally repairing both cartilage and bone could be achieved by designing multiple-cells distribution and a cell-induced bioink containing bioceramic particles. As an important bioactive agent, the Li-Mg-Si bioceramics-containing bioink exhibited the function of simultaneously stimulating multiple cells for differentiation towards specific directions. The 3D bioprinted co-culture scaffolds showed the capacity for osteochondral tissue regeneration by inducing osteogenic and chondrogenic differentiation in vitro and accelerating the repair of severe osteochondral defects in vivo. This study offers a potential strategy for complex tissue reconstruction through bioprinting multiple tissue cells in combination of bioceramics-stimulating bioinks.

Three-dimensional (3D) bioprinting is a revolutionary technology that replicates 3D functional living tissue scaffolds in vitro by controlling the layer-by-layer deposition of biomaterials and enables highly precise positioning of cells. With the development of this technology, more advanced research on the mechanisms of tissue morphogenesis, clinical drug screening, and organ regeneration may be pursued. Because of their self-renewal characteristics and multidirectional differentiation potential, induced pluripotent stem cells (iPSCs) have outstanding advantages in stem cell research and applications. In this review, we discuss the advantages of different bioinks containing human iPSCs that are fabricated by using 3D bioprinting. In particular, we focus on the ability of these bioinks to support iPSCs and promote their proliferation and differentiation. In addition, we summarize the applications of 3D bioprinting with iPSC-containing bioinks and put forward new views on the current research status.

It is a large clinical challenge to repair critical-size bone defects, and vascularization in the early stage is of vital importance in bone regeneration. In recent years, 3D-printed bioceramic is a kind of common bioactive scaffold for repairing bone defects. However, conventional 3D-printed bioceramic scaffolds consist of stacked solid struts with low porosity, which limits the ability of angiogenesis and bone regeneration. The hollow tube structure can induce endothelial cells to build the vascular system. In this study, β-tricalcium phosphate (β-TCP) bioceramic scaffolds containing the hollow tube structure were prepared with digital light processing-based 3D printing strategy. The physicochemical properties and osteogenic activities of prepared scaffolds could be precisely controlled by adjusting the parameters of hollow tubes. Compared with solid bioceramic scaffolds, such scaffolds could significantly improve the proliferation and attachment activity of rabbit bone mesenchymal stem cells in vitro, and facilitate early angiogenesis and subsequent osteogenesis in vivo. Therefore, β-TCP bioceramic scaffolds with the hollow tube structure possess great potential application for the treatment of critical-size bone defects.

The construction of hierarchical porous structure in biomaterials is of great significance for improving nutrient transport and biological performance. However, it is still challenging to design porous bone substitutes with high strength and biological properties, which limits their clinical applications in load-bearing bone regeneration. Herein, based on hierarchical porous structure of renewable bamboo, the mineralized calcium phosphate/bamboo composite scaffolds with high strength and excellent transport performance are successfully prepared in combination of biotemplated approach and biomimetic mineralization. The mineralized biomaterials have simultaneously achieved high mechanical strength and low modulus, similar to those of cortical bone. Furthermore, the mineralized biomaterials exhibit good liquid transport capacity and can transport cells along anti-gravity direction. Based on density functional theory (DFT) calculations, the mineralized calcium phosphate reveals the optimal H

The treatment of severe burn injuries is a crucial challenge in skin tissue engineering. Severe burns are always accompanied with large-area neurovascular networks damage, leading to the lack of excitation functions and difficulty in self-healing. Therefore, it is of great importance to develop biomaterials which can not only promote wound healing but also simultaneously reconstruct cutaneous neurovascular networks. In this study, Zn

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor‐initiated bone defects. Such scaffolds are usually composed of a near‐infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long‐term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR‐I) with intrinsic poor tissue penetration depth. Also, most of these agents are non‐bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR‐II photothermal conversion agent (Wesselsite [SrCuSi4O10] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as‐designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR‐II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor‐induced bone defects., An efficient multifunctional bone scaffold based on 3D printed SrCuSi4O10 nanosheets/polycaprolactone composite is developed as SC/PCL, which possesses excellent therapeutic effects for deep‐seated osteosarcoma due to its high photothermal‐conversion efficiency in the second biological window. Moreover, the as‐designed 3D composite scaffold could facilitate the vascularized bone regeneration via the sustained release of bioactive ions (Sr, Si, and Cu).

It is common to improve the relevant performance in the field of energy storage materials or catalytic materials by regulating the number of defects. However, there are few studies on the biomaterials containing defects for tissue engineering. Herein, a new type of defect-rich scaffolds, black akermanite (B-AKT) bioceramic scaffolds with micro/nanostructure, the thickness of which is from 0.14 to 1.94 µm, is fabricated through introducing defects on the surface of bioceramic scaffolds. The B-AKT scaffolds have advantages on the degradation rate and the osteogenic capacity over the AKT (Ca2 MgSi2 O7 ) scaffolds due to the surface defects which stimulate the osteogenic differentiation of rabbit bone mesenchymal stem cells via activating bone morphogenetic protein 2 （BMP2） signaling pathway and further promote bone formation in vivo. In addition, the prepared B-AKT scaffolds, the temperature of which can be over 100 °C under the near infrared （NIR） irradiation (0.66 W cm-2 ), possess excellent performance on photothermal and antitumor effects. The work develops an introducing-defect strategy for regulating the biological performance of bioceramic scaffolds, which is expected to be applied in the next generation of bioceramic scaffolds for regenerative medicine.

The clinical treatment of bone tumors usually brings about residual tumor cells and large bone defects after tumor removal surgery. To solve this problem, it is imperative to develop a novel implant with bi-functions for eliminating the residual tumor cells and repairing bone defects. In this study, hydrogenated black TiO2 (H-TiO2) coating with hierarchical micro/nano-topographies is fabricated by induction suspension plasma spraying (ISPS). The fabricated H-TiO2 coating possessed excellent and controllable photothermal effect in inhibiting the tumor growth under 808 nm NIR laser irradiation in vitro and in vivo. The hierarchical hybrid micro/nano-structured surface and Ti-OH groups improved the adhesion, proliferation, differentiation and osteogenic gene expressions of rat bone mesenchymal stem cells (rBMSCs). These results demonstrate that the H-TiO2 coating may be a promising implant material for the treatment of bone tumors and bone regeneration.

In the traditional surgical intervention procedure, residual tumor cells may potentially cause tumor recurrence. In addition, large bone defects caused by surgery are difficult to self-repair. Thus, it is necessary to design a bioactive scaffold that can not only kill residual tumor cells but also promote bone defect regeneration simultaneously. Here, we successfully developed Cu-containing mesoporous silica nanosphere-modified β-tricalcium phosphate (Cu-MSN-TCP) scaffolds, with uniform and dense nanolayers with spherical morphology via 3D printing and spin coating. The scaffolds exhibited coating time- and laser power density-dependent photothermal performance, which favored the effective killing of tumor cells under near-infrared laser irradiation. Furthermore, the prepared scaffolds favored the proliferation and attachment of rabbit bone marrow-derived mesenchymal stem cells and stimulated the gene expression of osteogenic markers. Overall, Cu-MSN-TCP scaffolds can be considered for complete eradication of residual bone tumor cells and simultaneous healing of large bone defects, which may provide a novel and effective strategy for bone tumor therapy. In the future, such Cu-MSN-TCP scaffolds may function as carriers of anti-cancer drugs or immune checkpoint inhibitors in chemo-/photothermal or immune-/photothermal therapy of bone tumors, favoring for effective treatment.

The challenges in bone tumor therapy are how to repair the large bone defects induced by surgery and kill all possible residual tumor cells. Compared to cancellous bone defect regeneration, cortical bone defect regeneration has a higher demand for bone substitute materials. To the best of our knowledge, there are currently few bifunctional biomaterials with an ultra-high strength for both tumor therapy and cortical bone regeneration. Here, we designed Fe-CaSiO3 composite scaffolds (30CS) via 3D printing technique. First, the 30CS composite scaffolds possessed a high compressive strength that provided sufficient mechanical support in bone cortical defects; second, synergistic photothermal and ROS therapies achieved an enhanced tumor therapeutic effect in vitro and in vivo. Finally, the presence of CaSiO3 in the composite scaffolds improved the degradation performance, stimulated the proliferation and differentiation of rBMSCs, and further promoted bone formation in vivo. Such 30CS scaffolds with a high compressive strength can function as versatile and efficient biomaterials for the future regeneration of cortical bone defects and the treatment of bone cancer. A method for three-dimensional printing of replacement bone that allows destruction of cancerous cells has been developed by scientists in China. Sometimes the only clinical approach to bone cancer is surgery that removes the affected tissue and replaces it with an artificial substitute. In the case of cortical bone, the dense tissue on a bone’s surface, the engineered biomaterial needs to be of very high strength. Chengtie Wu from the Shanghai Institute of Ceramics, CAS and colleagues demonstrated an iron-calcium silicate composite scaffold that is simple to produce and has the strength necessary to support the human body. The team used composite scaffold because it can be heated by near infrared light to kill residual cancer cells, a technique known as photothermal therapy. Adding iron increased the strength of the scaffold. Fe-CaSiO3 composite scaffolds (30CS) were designed via 3D printing technique. Firstly, 30CS scaffolds possessed high compressive strength to provide sufficient mechanical support in bone cortical defects; Secondly, a synergistic therapy of photothermal and ROS achieved enhanced tumor therapeutic effect in vitro and in vivo; Thirdly, the presence of CaSiO3 in the composite scaffolds enforced the degradation performance and stimulated proliferation and differentiation of rBMSCs and further promoted bone forming in vivo. Such 30CS scaffolds with high compressive strength can function as versatile and efficient biomaterials for the future regeneration of cortical bone defects and therapy of bone cancer.

It is a great challenge to endow the bioceramics with the bone-matched mechanical performances. Here, capturing inspiration from well ordered-microstructures in the high-performance natural composites, we propose a universal biomineralization-assembly-sintering approach for the fabrication of well ordered-microstructure meta-hydroxyapatite. Owing to the well ordered-microstructure and a new metal ions-related interface toughening mechanism, this well ordered-microstructure hydroxyapatite exhibits remarkable mechanical performances, which are far beyond those of existing hydroxyapatite-based bioceramic and totally matched with the human cortical bone. Furthermore, the ordered microstructure plays a significant role in modulating the cell fates and finally stimulating bone defects regeneration in vivo. This work not only provides a strategy for the fabrication of well ordered-microstructure bioceramic but also broadens the horizons for the interface toughening mechanism of composites and microstructure design of biomaterials for bone regeneration.

The development of a rapid-forming in-situ sprayable hydrogel with the functions of tumor treatment and wound healing is essential for eliminating residual tumor tissue and promoting wound healing caused by surgical resection. On account of its semiconductor properties, β-FeSi2 (FS) was widely explored as a thermoelectric material. In this work, FS was first applied as a bioactive material for the application of tissue engineering. Excitedly, we found that FS could be used as a novel antitumor agent. It exhibited excellent photothermal performance, and the released Fe ions could generate •OH under the acidic conditions and excessive H2O2 in the tumor microenvironment. Moreover, the sprayable β-FeSi2-incorporated sodium alginate (FS/SA) hydrogel was prepared as an instant gelation after spraying in situ, contributing to timely tumor-induced skin wound healing and efficiently suppressing tumors through photothermal and chemodynamic therapy (PTT and CDT). Furthermore, the released bioactive Fe and Si ions could promote the migration and differentiation of endothelial cells and the pro-angiogenesis of skin wounds. Accordingly, such sprayable hydrogel played an effective role in emergency wound treatment with the advantage of convenience and portability. Overall, with incorporation of FS into the sprayable FS/SA hydrogel, the composite hydrogel possessed dual functions of tumor therapy and skin wound healing.

Bone is a complex mineralized tissue composed of various organic (proteins, cells) and inorganic (hydroxyapatite, calcium carbonate) substances with micro/nanoscale structures. To improve interfacial bioactivity of bone-implanted biomaterials, extensive efforts are being made to fabricate favorable biointerface via surface modification. Inspired by microbially catalyzed mineralization, a novel concept to biologically synthesize the micro/nanostructures on bioceramics, microbial-assisted catalysis, is presented. It involves three processes: bacterial adhesion on biomaterials, production of CO3 2- assisted by bacteria, and nucleation and growth of CaCO3 nanocrystals on the surface of bioceramics. The microbially catalyzed biominerals exhibit relatively uniform micro/nanostructures on the surface of both 2D and 3D α-CaSiO3 bioceramics. The topographic and chemical cues of the grown micro/nanostructures present excellent in vitro and in vivo bone-forming bioactivity. The underlying mechanism is closely related to the activation of multiple biological processes associated with bone regeneration. The study offers a microbially catalytic concept and strategy of fabricating micro/nanostructured biomaterials for tissue regeneration.

The therapeutic effects of mesenchymal stem cells (MSCs)-material constructs mainly come from the secretion of trophic factors from MSCs, especially the immunomodulatory and angiogenic cytokines. Recent findings indicate the significance of topographical cues from these materials in modulating paracrine functions of MSCs. Here, we developed functionalized three-dimensional-printed bioceramic (BC) scaffolds with a mussel-inspired surface coating in order to regulate the paracrine function of adipose-derived MSCs (Ad-MSCs). We found that Ad-MSCs cultured on polydopamine-modified BC scaffolds (DOPA-BC) significantly produced more immunomodulatory and pro-angiogenic factors when compared with those cultured on BC scaffolds or microplates. Functional assays, such as endothelial progenitor cells migration, tube formation, and macrophage polarization, were performed to confirm the enhanced paracrine functions of the secreted trophic factors from Ad-MSCs cultured on DOPA-BC scaffolds. Further investigation identified that both focal adhesion kinase- and extracellular signal-related kinase signaling were the required mechano-transduction pathways through which the mussel-inspired surface stimulated the paracrine effect of Ad-MSCs. In a diabetic skin-defect-healing model in rats, conditioned medium received from the Ad-MSCs cultured on DOPA-BC sped wound closure, enhanced vascularization, and promoted macrophage switching from a proinflammatory M1 to a pro-healing and anti-inflammatory M2 phenotype in the wound bed. These results demonstrate that a bio-inspired coating with polydopamine represents an effective method to enhance the paracrine function of MSCs. Our findings illustrate a novel strategy to accelerate tissue regeneration by guiding the paracrine-signaling network.

Grape-seed extracts contain rich flavonoids with oligomeric proanthocyanidins (OPC). In this study, OPC containing hydrogel scaffolds can function as a natural photothermal agent for melanoma therapy and bioactive biomaterial for wound healing. Inspired by grape-seed extracts, OPC were explored as a photothermal agent and endowed the hydrogel scaffolds with excellent and controlled photothermal ability. The rheological property of the hydrogel scaffolds responded to irradiation time of near infrared (NIR) laser, and OPC contents. The compressive mechanical property of the hydrogel scaffolds was well modulated by NIR laser irradiation with different impact durations. The controlled high temperature induced by OPC-containing hydrogel scaffolds under NIR laser irradiation could effectively kill melanoma cells and suppress tumor growth. In addition, OPC-containing hydrogel scaffolds supported the proliferation and migration of human dermal fibroblasts and human umbilical vein endothelial cells, as well as obviously promoted angiogenesis and skin regeneration in both tumor-caused and chronic wounds. Therefore, OPC-containing hydrogel scaffolds possessed controlled photothermal, rheological, and compressive mechanical properties under NIR laser stimuli, as well as excellent biocompatibility and bioactivity for melanoma therapy and wound healing.

After online publication of this article, the authors noticed an error of Fig. 3h in Fig. 3. The correct Fig. 3 of this article should have read as below.

The clinical treatment of bone tumors usually brings about residual tumor cells and large bone defects after tumor removal surgery. To solve this problem, it is imperative to develop a novel implant with bi-functions for eliminating the residual tumor cells and repairing bone defects. In this study, hydrogenated black TiO

Effectively stimulating angiogenesis and avoiding wound infection are great challenges in wound care management. Designing new healing dressings with requisite angiogenic capacity and antibacterial performance is of particular significance. In order to achieve this aim, we prepared a copper (Cu)-containing bioactive glass nanocoating (40–50 nm) with uniform nanostructure on natural eggshell membrane (Cu-BG/ESM) by the pulsed laser deposition (PLD) technique. The surface physicochemical properties including hydrophilicity and hardness of ESM were significantly improved after depositing Cu-BG nanocoatings. Meanwhile, 5Cu-BG/ESM films containing 5 mol% Cu stimulated proangiogenesis by improving vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α protein secretion as well as angiogenesis-related gene expression (VEGF, HIF-1α, VEGF receptor 2 (KDR) and endothelial nitric oxide (eNos)) of human umbilical vein endothelial cells (HUVECs). When used to treat full-thickness skin defects in mice, 5Cu-BG/ESM films enhanced the healing quality as confirmed by the significantly improved angiogenesis (as indicated by CD31 expression) and formation of continuous and uniform epidermis layer in vivo . Furthermore, 5Cu-BG/ESM films could maintain a sustained release of Cu 2+ ions and distinctly inhibited the viability of bacteria ( Escherichia coli ). The results indicate that Cu 2+ ions released from Cu-BG/ESM nanocomposite films play an important role for improving both angiogenesis and antibacterial activity and the prepared nanocomposite films combined Cu-containing BG nanocoatings with ESM are a promising biomaterial for wound healing application. Statement of Significance Designing new healing dressings with requisite angiogenic capacity and antibacterial performance is of particular significance in wound care management. In our study, we successfully prepared copper-containing bioactive glass/eggshell membrane (Cu-BG/ESM) nanocomposites with uniform bioactive glass nanocoatings by using pulsed laser deposition (PLD) technology. Due to the deposited Cu-BG nanocoatings on the surface of ESM, Cu-BG/ESM nanocomposites possessed significantly improved physicochemical and biological properties, including surface hydrophilicity, hardness, antibacterial ability, angiogenesis rate in vitro and wound healing quality in vivo as compared to pure ESM and BG/ESM films. Our study showed that prepared nanocoatings on Cu-BG/ESM nanocomposites offer a beneficial carrier for sustained release of Cu 2+ ions which played a key role for improving both angiogenesis and antibacterial activity. The prepared nanocomposites combined Cu-containing BG nanocoatings with ESM are a promising biomaterial for wound healing application.

Toward the aim of personalized treatment, three-dimensional (3D) printing technology has been widely used in bone tissue engineering owing to its advantage of a fast, precise, and controllable fabrication process. Conventional bioceramic scaffolds are mainly used for bone tissue engineering; however, there has been a significant change in the application of bioceramic scaffolds during the past several years. Therefore, this review focuses on 3D-printed bioceramic scaffolds with different compositions and hierarchical structures (macro, micro, and nano scales), and their effects on the mechanical, degradation, permeability, and biological properties. Further, this review highlights 3D-printed bioceramic scaffolds for applications extending from bone tissue regeneration to bone tumor therapy. This review emphasizes recent developments in functional 3D-printed bioceramic scaffolds with the ability to be used for both tumor therapy and bone tissue regeneration. Considering the challenges in bone tumor therapy, these functional bioceramic scaffolds have a great potential in repairing bone defects induced by surgery and kill the possibly residual tumor cells to achieve bone tumor therapy. Finally, a brief perspective regarding future directions in this field was also provided. The review not only gives a summary of the research developments in bioceramic science but also offers a new therapy strategy by extending multifunctions of traditional biomaterials toward a specific disease. Statement of significance This review outlines the development tendency of 3D-printed bioceramic scaffolds for applications ranging from bone tissue regeneration to bone tumor therapy. Conventional bioceramic scaffolds are mainly used for bone tissue engineering; however, there has been a significant change in the application of bioceramic scaffolds during the past several years. Therefore, this review focuses on 3D-printed bioceramic scaffolds with different compositions and hierarchical structures (macro, micro, and nano scales), and their effects on the mechanical, degradation, permeability, and biological properties. Further, this review highlights 3D-printed bioceramic scaffolds for applications extending from bone tissue regeneration to bone tumor therapy. This review emphasizes recent developments in the functional 3D-printed bioceramic scaffolds with the ability to be used for both bone tumor therapy and bone tissue regeneration.

Bone tumor is one of major challenging issues clinically. After surgical intervention, a few bone tumor cells still remain around bone defects and then proliferate over days. Fabrication of specific biomaterials with dual functions of bone tumor therapy and bone defect regeneration is of great significance. In order to achieve this aim, we managed to prepare bioactive glass (BG) scaffolds functionalized by the CuFeSe2 nanocrystals (BG-CFS) by combining 3D printing technique with solvothermal method. During the solvothermal reaction process, CuFeSe2 nanocrystals could in situ grow on the strut surface of BG scaffolds and thus endow BG scaffolds excellent photothermal performance. The photothermal performance of BG-CFS scaffolds could be well regulated through altering the content of CuFeSe2 nanocrystals and laser power density when exposed to the near infrared laser (808 nm). The BG-CFS scaffolds could not only effectively ablate the bone tumor cells (Saos-2 cells) in vitro, but also significantly inhibit bone tumor growth in vivo. Moreover, BG-CFS scaffolds could stimulate osteogenic gene expression of rabbit bone marrow stromal cells (rBMSCs) and finally facilitate the formation of new bone in the bone defects. Our study, for the first time, combined the photothermal performance of semiconductor CuFeSe2 nanocrystals with the bone-forming activity of bioactive glass scaffolds, which can offer a more extensive horizon for developing novel biomaterials with dual functions of bone tumor therapy and bone regeneration.

For treatment of bone tumor and regeneration of bone defects, the biomaterials should possess the ability to kill tumor cells and regenerate bone defect simultaneously. To date, there are a few biomaterials possessing such dual functions, the disadvantages, however, such as long-term toxicity and degradation, restrict their application. Although bioactive elements have been incorporated into biomaterials to improve their osteogenic activity, there is no report about elements-induced functional scaffolds for photothermal tumor therapy. Herein, the elements (Cu, Fe, Mn, Co)-doped bioactive glass-ceramic (BGC) scaffolds with photothermal effect and osteogenic differentiation ability were prepared via 3D-printing method. Moreover, the photothermal anti-tumor effect and osteogenic activity of these scaffolds were systematically investigated. The prepared elements-doped scaffolds possessed excellent photothermal performance, which displayed a trend, 5Cu-BGC > 5Fe-BGC > 5Mn-BGC > 5Co-BGC, in this study. The final temperature of elements-doped scaffolds can be well controlled by altering the doping element categories, contents and laser power density. Additionally, the hyperthermia induced by 5Cu-BGC, 5Fe-BGC and 5Mn-BGC effectively killed tumor cells in vitro and inhibited tumor growth in vivo. More importantly, 5Fe-BGC and 5Mn-BGC scaffolds could promote rabbit bone mesenchymal stem cells (rBMSCs) adhesion, and the ionic products released from elements-doped scaffolds significantly stimulated the osteogenic differentiation of bone-forming cells. These results suggested that 5Fe-BGC and 5Mn-BGC scaffolds possessed promising potential for photothermal treatment of bone tumor and at the same time for stimulating bone regeneration, representing a smart strategy for the treatment of bone tumors by combining dual functional bioactive ions with tissue engineering scaffolds. Statement of Significance The major innovation of this study is that we fabricated the elements (Cu, Fe, Mn, Co)-doped bioactive scaffolds via 3D printing technique and found that they possess distinct photothermal performance and osteogenic differentiation ability. To the best of our knowledge, there is no report about elements-doped scaffolds for photothermal therapy of bone tumor. This is an important research advance by combining the photothermal effect and osteogenic differentiation activity of bioactive elements in the scaffold system for potential bone tumor therapy and bone reconstruction. We optimized the elements-doped scaffolds and found the photothermal effect of elements-doped scaffolds (5Cu-BGC, 5Fe-BGC, 5Mn-BGC) could effectively kill tumor cells in vivo. The photothermal performance of elements-doped scaffolds follows a trend: 5Cu-BGC > 5Fe-BGC > 5Mn-BGC > 5Co-BGC > BGC. Compared to traditional nano-sized photothermal agents, bioactive elements-induced functional scaffolds have better biosecurity and bioactivity. Furthermore, 5Fe-BGC and 5Mn-BGC scaffolds displayed excellent bone-forming activity by stimulating the osteogenic differentiation of bone-forming cells. The major significance of the study is that the elements-doped bioactive glass-ceramics (5Fe-BGC, 5Mn-BGC) have great potential to be used as bifunctional scaffolds for photothermal tumor therapy and bone regeneration, representing a smart strategy for the treatment of bone tumors by combining dual functional bioactive ions with tissue engineering scaffolds.

Bone tumor is one of major challenging issues clinically. After surgical intervention, a few bone tumor cells still remain around bone defects and then proliferate over days. Fabrication of specific biomaterials with dual functions of bone tumor therapy and bone regeneration is of great significance. In order to achieve this aim, we managed to prepare bioactive glass (BG) scaffolds functionalized by the CuFeSe

Bone cancer brings patients great sufferings and puts an end to normal activities in life. In clinic, the most common treatment for bone cancer is the combination of surgery and chemo-/radiotherapy. However, surgery is difficult to eliminate tumor cells completely and results in large bone defect. Chemo-/radiotherapy is associated with chemo-/radioresistance and evident short-/long-term toxic effects. Therefore, the development of a novel bio-scaffold for local treatment of residual tumor cells and regeneration of bone defect induced by surgery has become a very urgent need. Some progress has been made in the development of scaffolds with the ability of both tumor therapy and bone regeneration. These scaffolds function as local agents and selectively kill the tumor cells via photothermal/magnetothermal therapy or local chemotherapy. Compared with traditional treatment, they have no side effects. In addition, scaffolds possess satisfactory biocompatibility, stimulating the migration, adhesion, proliferation, and differentiation of bone marrow stroma cells. Furthermore, they can promote gene expression of BMSCs and formation of new bone. Therefore, to bone tumor-suffering patients, it is a very meaningful progress in the biomedical application. Hopefully, more efforts and progress will be made in the development of scaffolds for the treatment of tumor-induced bone defects, and more research will continue to inform and guide this field.

Diabetic wound is a common complication of diabetes. Biomaterials offer great promise in inducing tissue regeneration for chronic wound healing. Herein, we reported a conducive Poly (caprolactone) (PCL)/gelatin nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca 7 P 2 Si 2 O 16 ) for diabetic wound healing. NAGEL bioceramic particles were well distributed in the inner of PCL/gelatin nanofibers via co-electrospinning process and the Si ions maintained a sustained release from the composite scaffolds during the degradation process. The nanofibrous scaffolds significantly promoted the adhesion, proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human keratinocytes (HaCaTs) in vitro . The in vivo study demonstrated that the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization in the wound sites of diabetic mice model, as well as inhibited inflammation reaction. The mechanism for nanofibrous composite scaffolds accelerating diabetic wound healing is related to the activation of epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) pathway in vivo and in vitro . Our results suggest that the released Si ions and nanofibrous structure of scaffolds have a synergetic effect on the improved efficiency of diabetic wound healing, paving the way to design functional biomaterials for tissue engineering and wound healing applications. Statement of Significance In order to stimulate tissue regeneration for chronic wound healing, a new kind of conducive nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca 7 P 2 Si 2 O 16 ) were prepared via co-electrospinning process. Biological assessments revealed that the NAGEL bioceramic particles could active epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) pathway in vitro and in vivo . The new composite scaffold had potential as functional biomaterials for tissue engineering and wound healing applications. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors on nanofibrous composite scaffold provides new options for bioactive biomaterials.

Forty polymorphic microsatellite loci were developed from Crassostrea hongkongensis using an enriched partial genomic library with magnetic beads. The polymorphism of these loci was assessed in 30 individuals from a wild population. The allele number of the polymorphic markers ranged from 2 to 13, with an average of 5.8 per locus. The polymorphism information content ranged from 0.032 to 0.891 and 37 loci presented a medium or high level of polymorphism. The observed and expected heterozygosity values ranged from 0.033 to 1.000 and 0.033 to 0.931, respectively. Of the 40 loci, 28 were found to conform to Hardy-Weinberg equilibrium (HWE), whereas the remaining 12 showed a significant departure from HWE. The availability of these markers will aid future genetic studies in C. hongkongensis.

Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects.

The treatment of malignant bone tumors is a significant clinical challenge because it requires the simultaneous removal of tumor tissues and regeneration of bone defects, and bifunctional three-dimensional (3D) scaffolds that function in both tumor therapy and tissue regeneration are expected to address this need. In this study, novel bifunctional scaffolds (MS-AKT scaffolds) were successfully fabricated by combining a 3D printing technique with a hydrothermal method. During the hydrothermal process, MoS2 nanosheets were grown in situ on the strut surface of bioceramic scaffolds, endowing them with photothermal therapeutic potential. Under near-infrared (NIR) irradiation, the temperature of the MS-AKT scaffolds rapidly increased and was effectively modulated by varying the MoS2 content, scaffold sizes and laser power densities. The photothermal temperature significantly decreased the viability of osteosarcoma cells and breast cancer cells and inhibited tumor growth in vivo. Moreover, the MS-AKT scaffolds supported the attachment, proliferation and osteogenic differentiation of bone mesenchymal stem cells and induced bone regeneration in vivo. This bifunctional scaffold, which treats the tumor and facilitates bone growth, offers a promising clinical strategy to treat tumor-induced bone defects. This proof-of-concept study demonstrates the feasibility of localized tumor therapy and tissue regeneration in diverse tissue engineering applications using multifunctional biomaterials. Molybdenum disulfide (MoS2) nanosheets grown on a bioceramic scaffold are promising for improved treatment of malignant bone tumours. Treating malignant bone tumours is challenging as it requires removing tumour tissues while simultaneously regenerating bone defects. Current treatments combine surgery, chemotherapy and radiotherapy, which can result in incomplete removal of tumour cells, large bone defects and other harmful side effects. Now, Chengtie Wu of the Shanghai Institute of Ceramics, China, and co-workers have used hydrothermal processing to grow MoS2 nanosheets on three-dimensional printed bioceramic scaffolds. The photothermal properties of these nanosheets can be used to generate heating in the vicinity of tumours, thereby inhibiting their growth, while the scaffolds provide support for bone regeneration. The bifunctional scaffold potentially could be used to clinically treat tumour-induced bone defects. A bifunctional scaffold was successfully prepared by in situ growth of MoS2 nanosheets on the 3D-printed bioceramic scaffolds via a facile hydrothermal process. The prepared scaffolds exhibit an excellent capability for both tumor therapy and tissue regeneration, offering a promising clinical strategy for effective treatment of tumor-induced tissue defects.

Polymer biomaterials have been widely used for bone replacement/regeneration because of their unique mechanical properties and workability. Their inherent low bioactivity makes them lack osseointegration with host bone tissue. For this reason, bioactive inorganic particles have been always incorporated into the matrix of polymers to improve their bioactivity. However, mixing inorganic particles with polymers always results in inhomogeneity of particle distribution in polymer matrix with limited bioactivity. This study sets out to apply the pulsed laser deposition (PLD) technique to prepare uniform akermanite (Ca2MgSi2O7, AKT) glass nanocoatings on the surface of two polymers (non-degradable polysulfone (PSU) and degradable polylactic acid (PDLLA)) in order to improve their surface osteogenic and angiogenic activity. The results show that a uniform nanolayer composed of amorphous AKT particles (∼30 nm) of thickness 130 nm forms on the surface of both PSU and PDLLA films with the PLD technique. The prepared AKT-PSU and AKT-PDLLA films significantly improved the surface roughness, hydrophilicity, hardness and apatite mineralization, compared with pure PSU and PDLLA, respectively. The prepared AKT nanocoatings distinctively enhance the alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, OPN and Col I) of bone-forming cells on both PSU and PDLLA films. Furthermore, AKT nanocoatings on two polymers improve the attachment, proliferation, VEGF secretion and expression of proangiogenic factors and their receptors of human umbilical vein endothelial cells (HUVEC). The results suggest that PLD-prepared bioceramic nanocoatings are very useful for enhancing the physicochemical, osteogenic and angiogenic properties of both degradable and non-degradable polymers for application in bone replacement/regeneration.

The intervertebral disc (IVD) is a heterogeneous structure that contributes to load support and flexibility in the spine. IVD cells experience a broad range of physical stimuli under physiological conditions, including alterations in their osmotic environment. To date, the molecular mechanisms regulating the response of IVD to osmotic pressure are still not well understood. We obtained the gene expression profile of human IVD cells from NCBI and looked for potential therapeutic drug candidates. Based on microarray data, we concluded that RAP2A and GNA13 appear to have a role in response to osmotic stimuli in intervertebral discs. Using a computational bioinformatics method, we determined that thioridazine has potential as a therapeutic drug candidate for regulating osmotic pressure changes in IVD cells. We anticipate that our results will be used to generate hypotheses for laboratory, patient, and population-based studies.

One-dimensional (WO3/LiF)N photonic crystals (1DPCs) are deposited on the Ag cathode of the semitransparent polymer solar cells to improve the efficiency of the device. The 1DPCs with 8 pair of WO3/LiF act as distributed reflectors within the photonic bandgap. Then, power conversion efficiency of 2.58% is achieved and there is an improvement of 26.3% in the efficiency when compared with that of the conventional device without the 1DPCs. The average transmittance of the device with 8 pair of WO3/LiF is almost zero in 400–600 nm wavelength range. It means that the light is absorbed sufficiently in the active layer. The enhanced light absorption results in efficiency improvement remarkably.