3D modular bioceramic scaffolds for the investigation of the interaction between osteosarcoma cells and MSCs.

Recent advances in bone tissue engineering have shown promise for bone repair post osteosarcoma excision. However, conflicting research on mesenchymal stem cells (MSCs) has raised concerns about their potential to either promote or inhibit tumor cell proliferation. It is necessary to thoroughly understand the interactions between MSCs and tumor cells. Most previous studies only focused on the interactions between cells within the tumor tissues. It has been challenging to develop an in vitro model of osteosarcoma excision sites replicating the complexity of the bone microenvironment and cell distribution. In this work, we designed and fabricated modular bioceramic scaffolds to assemble into a co-culture model. Because of the bone-like composition and mechanical property, tricalcium phosphate bioceramic could mimic the bone microenvironment and recapitulate the cell-extracellular matrix interaction. Moreover, the properties for easy assembly enabled the modular units to mimic the spatial distribution of cells in the osteosarcoma excision site. Under this co-culture model, MSCs showed a noticeable tumor-stimulating effect with a potential risk of tumor recurrence. In addition, tumor cells also could inhibit the osteogenic ability of MSCs. To undermine the stimulating effects of MSCs on tumor cells, we present the methods of pre-differentiated MSCs, which had lower expression of IL-8 and higher expression of osteogenic proteins. Both in vitro and in vivo studies confirm that pre-differentiated MSCs could maintain high osteogenic capacity without promoting tumor growth, offering a promising approach for MSCs' application in bone regeneration. Overall, 3D modular scaffolds provide a valuable tool for constructing hard tissue in vitro models. STATEMENT OF SIGNIFICANCE: Bone tissue engineering using mesenchymal stem cells (MSCs) and biomaterials has shown promise for bone repair post osteosarcoma excision. However, conflicting researches on MSCs have raised concerns about their potential to either promote or inhibit tumor cell proliferation. It remains challenges to develop in vitro models to investigate cell interactions, especially of osteosarcoma with high hardness and special composition of bone tissue. In this work, modular bioceramic scaffolds were fabricated and assembled to co-culture models. The interactions between MSCs and MG-63 were manifested as tumor-stimulating and osteogenesis-inhibiting, which means potential risk of tumor recurrence. To undermine the stimulating effect, pre-differentiation method was proposed to maintain high osteogenic capacity without tumor-stimulating, offering a promising approach for MSCs' application in bone regeneration.

Assembled/Disassembled Modular Scaffolds for Multicellular Tissue Engineering.

The behavior of tissue resident cells can be influenced by the spatial arrangement of cellular interactions. Therefore, it is of significance to precisely control the spatial organization of various cells within multicellular constructs. It remains challenging to construct a versatile multicellular scaffold with ordered spatial organization of multiple cell types. Herein, a modular multicellular tissue engineering scaffold with ordered spatial distribution of different cell types is constructed by assembling varying cell-laden modules. Interestingly, the modular scaffolds can be disassembled into individual modules to evaluate the specific contribution of each cell type in the system. Through assembling cell-laden modules, the macrophage-mesenchymal stem cell (MSC), endothelial cell-MSC, and chondrocyte-MSC co-culture models are successfully established. The in vitro results indicate that the intercellular cross-talk can promote the proliferation and differentiation of each cell type in the system. Moreover, MSCs in the modular scaffolds may regulate the behavior of chondrocytes through the nuclear factor of activated T-Cells (NFAT) signaling pathway. Furthermore, the modular scaffolds loaded with co-cultured chondrocyte-MSC exhibit enhanced regeneration ability of osteochondral tissue, compared with other groups. Overall, this work offers a promising strategy to construct a multicellular tissue engineering scaffold for the systematic investigation of intercellular cross-talk and complex tissue engineering.

Design and synthesis of bioinspired nanomaterials for biomedical application.

Natural materials and bioprocesses provide abundant inspirations for the design and synthesis of high-performance nanomaterials. In the past several decades, bioinspired nanomaterials have shown great potential in the application of biomedical fields, such as tissue engineering, drug delivery, and cancer therapy, and so on. In this review, three types of bioinspired strategies for biomedical nanomaterials, that is, inspired by the natural structures, biomolecules, and bioprocesses, are mainly introduced. We summarize and discuss the design concepts and synthesis approaches of various bioinspired nanomaterials along with their specific roles in biomedical applications. Additionally, we discuss the challenges for the development of bioinspired biomedical nanomaterials, such as mechanical failure in wet environment, limitation in scale-up fabrication, and lack of deep understanding of biological properties. It is expected that the development and clinical translation of bioinspired biomedical nanomaterials will be further promoted under the cooperation of interdisciplinary subjects in future. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Xonotlite Nanowire-Containing Bioactive Scaffolds for the Therapy of Defective Adipose Tissue in Breast Cancer.

Considering the challenge in the treatment of severe breast tumor patients, xonotlite nanowire-containing bioactive scaffolds (Fe3O4-CS-GelMA) were fabricated by the 3D-printing technique for the therapy of injured adipose tissue after surgery. Importantly, benefiting from the excellent magnetothermal performance of Fe3O4 microspheres, Fe3O4-CS-GelMA scaffolds could effectively kill tumor cells in vitro and suppress breast cancer in vivo under an alternating magnetic field, and the tumor did not recur in 2 weeks. In addition, attributed to the released bioactive inorganic ions, Fe3O4-CS-GelMA composite scaffolds could effectively promote the expression of adipogenesis-related genes and proteins of adipose-derived stem cells (ADSCs) via the PI3K-AKT signaling pathway in vitro. Furthermore, Fe3O4-CS-GelMA scaffolds with ADSCs could obviously stimulate the formation of adipose in vivo, compared with that of pure GelMA without inorganic components. Therefore, this study offers a promising strategy for the therapy of breast tumors after the surgical excision of breast carcinoma.

Lithium-Containing Biomaterials Stimulate Cartilage Repair through Bone Marrow Stromal Cells-Derived Exosomal miR-455-3p and Histone H3 Acetylation.

The repair of damaged cartilage still remains a great challenge in clinic. It is demonstrated that bone marrow stromal cells (BMSCs)-chondrocytes communication is of great significance for cartilage repair. Moreover, BMSCs have been confirmed to enhance biological function of chondrocytes via exosome-mediated paracrine pathway. Lithium-containing scaffolds have been reported to effectively promote cartilage regeneration; however, whether lithium-containing biomaterial could facilitate cartilage regeneration through regulating BMSCs-derived exosomes has not been illustrated. In the study, the model lithium-substituted bioglass ceramic (Li-BGC) is selected and regulatory effects of BMSCs-derived exosomes after Li-BGC treatment (Li-BGC-Exo) are systemically evaluated. The data reveal that Li-BGC-Exo notably promotes chondrogenesis, which attributes to the upregulated exosomal miR-455-3p transfer, consequently leads to suppression of histone deacetylase 2 (HDAC2) and enhanced histone H3 acetylation in chondrocytes. Notably, BMSCs-derived exosomes after LiCl treatment (LiCl-Exo) exhibits the similar regulatory effect with Li-BGC-Exo, indicating that the pro-chondrogenesis capability of them is mainly owing to the lithium ions. Furthermore, the in vivo study proves that LiCl-Exo remarkably facilitates cartilage regeneration. The research may provide novel possibility for the intrinsic mechanism of chondrogenesis trigged by lithium-containing biomaterials, and suggests that application of lithium-containing scaffolds may be a promising strategy for cartilage regeneration.

Engineering lactate-modulating nanomedicines for cancer therapy.

Lactate in tumors has long been considered "metabolic junk" derived from the glycolysis of cancer cells and utilized only as a biomarker of malignancy, but is presently believed to be a pivotal regulator of tumor development, maintenance and metastasis. Indeed, tumor lactate can be a "fuel" for energy supply and functions as a signaling molecule, which actively contributes to tumor progression, angiogenesis, immunosuppression, therapeutic resistance, etc., thus providing promising opportunities for cancer treatment. However, the current approaches for regulating lactate homeostasis with available agents are still challenging, which is mainly due to the short half-life, low bioavailability and poor specificity of these agents and their unsatisfactory therapeutic outcomes. In recent years, lactate modulation nanomedicines have emerged as a charming and efficient strategy for fighting cancer, which play important roles in optimizing the delivery of lactate-modulating agents for more precise and effective modulation and treatment. Integrating specific lactate-modulating functions in diverse therapeutic nanomedicines may overcome the intrinsic restrictions of different therapeutic modalities by remodeling the pathological microenvironment for achieving enhanced cancer therapy. In this review, the most recent advances in the engineering of functional nanomedicines that can modulate tumor lactate for cancer therapy are summarized and discussed, and the fundamental mechanisms by which lactate modulation benefits various therapeutics are elucidated. Finally, the challenges and perspectives of this emerging strategy in the anti-tumor field are highlighted.

Nano-calcium silicate mineralized fish scale scaffolds for enhancing tendon-bone healing.

Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery, however, this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity. Inspired by the high-performance exoskeleton of natural organisms, we set out to apply natural fish scale (FS) modified by calcium silicate nanoparticles (CS NPs) as a new biomaterial (CS-FS) to overcome the challenge. Benefit from its "Bouligand" microstructure, such FS-based scaffold maintained excellent tensile strength (125.05 MPa) and toughness (14.16 MJ/m3), which are 1.93 and 2.72 times that of natural tendon respectively, allowing it to well meet the requirements for rotator cuff tendon repair. Additionally, CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction, (e.g. bone marrow mesenchymal stem cells (BMSCs), chondrocyte, and tendon stem/progenitor cells (TSPCs)). In both rat and rabbit rotator cuff tear (RCT) models, CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function, which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs. Therefore, natural fish scale -based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.

Microneedle-Assisted Transdermal Delivery of 2D Bimetallic Metal-Organic Framework Nanosheet-Based Cascade Biocatalysts for Enhanced Catalytic Therapy of Melanoma.

Current conventional treatments for malignant melanoma still face limitations, especially low therapeutic efficacy and serious side effects, and more effective strategies are urgently needed to develop them. Delivering biocatalysts into tumors to efficiently trigger in situ cascade reactions has shown huge potential in producing more therapeutic species or generating stronger tumoricidal effects for augmented tumor therapy. Recently, ultrathin 2D metal-organic framework (MOF) nanosheets have acquired great interest in biocatalysis owing to their large surface areas and abundant accessible active catalytic sites. Herein, an enhanced catalytic therapeutic strategy against melanoma is developed by biocompatible microneedle (MN)-assisted transdermal delivery of a 2D bimetallic MOF nanosheet-based cascade biocatalyst (Cu-TCPP(Fe)@GOD). Profiting from the constructed dissolving MN system, the loaded Cu-TCPP(Fe)@GOD hybrid nanosheets can be accurately delivered into the melanoma sites through skin barriers, and subsequently, trigger the specific cascade catalytic reactions in response to the acidic tumor microenvironment to effectively generate highly toxic hydroxyl radical (• OH) and deplete glucose nutrient for inducing the death of melanoma cells. The ultimate results prove the high melanoma inhibition effect and biosafety of such therapeutic modality, exhibiting a new and promising strategy to conquer malignant melanoma.

Cells-Micropatterning Biomaterials for Immune Activation and Bone Regeneration.

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/ß-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.

Bioceramic-based scaffolds with antibacterial function for bone tissue engineering: A review.

Bone defects caused by trauma, tumor, congenital abnormality and osteoarthritis, etc. have been substantially impacted the lives and health of human. Artificial bone implants, like bioceramic-based scaffolds, provide significant benefits over biological counterparts and are critical for bone repair and regeneration. However, it is highly probable that bacterial infections occur in the surgical procedures or on bioceramic-based scaffolds. Therefore, it is of great significance to obtain bioceramic-based scaffolds with integrative antibacterial and osteogenic functions for treating bone implant-associated infection and promoting bone repair. To fight against infection problems, bioceramic-based scaffolds with various antibacterial strategies are developed for bone repair and regeneration and also have made great progresses. This review summarizes recent progresses in bioceramic-based scaffolds with antibacterial function, which include drug-induced, ion-mediated, physical-activated and their combined antibacterial strategies according to specific antibacterial mechanism. Finally, the challenges and opportunities of antibacterial bioceramic-based scaffolds are discussed.

Role of molybdenum in material immunomodulation and periodontal wound healing: Targeting immunometabolism and mitochondrial function for macrophage modulation.

Recently, strategies that can target the underlying mechanisms of phenotype change to modulate the macrophage immune response from the standpoint of biological science have attracted increasing attention in the field of biomaterials. In this study, we printed a molybdenum-containing bioactive glass ceramic (Mo-BGC) scaffold as an immunomodulatory material. In a clinically relevant critical-size periodontal defect model, the defect-matched scaffold featured robust immunomodulatory activity, enabling long-term stable macrophage modulation and leading to enhanced regeneration of multiple periodontal tissues in canines. Further studies demonstrated that the regeneration-enhancing function of Mo-BGC scaffold was macrophage-dependent by using canines with host macrophage depletion. To investigate the role of Mo in material immunomodulation, in vitro investigations were performed and revealed that Mo-BGC powder extract, similar to MoO42--containing medium, induced M2 polarization by enhancing the mitochondrial function of macrophages and promoted a cell metabolic shift from glycolysis toward mitochondrial oxidative phosphorylation. Our findings demonstrate for the first time an immunomodulatory role of a Mo-containing material in the dynamic cascade of wound healing. By targeting the immunometabolism and mitochondrial function of macrophages, Mo-mediated immunomodulation provides new avenues for future material design in the field of tissue engineering and regenerative medicine.

Bioceramic Scaffolds with Antioxidative Functions for ROS Scavenging and Osteochondral Regeneration.

Osteoarthritis (OA) is a degenerative disease that involves excess reactive oxygen species (ROS) and osteochondral defects. Although multiple approaches have been developed for osteochondral regeneration, how to balance the biochemical and physical microenvironment in OA remains a big challenge. In this study, a bioceramic scaffold by 3D printed akermanite (AKT) integrated with hair-derived antioxidative nanoparticles (HNPs)/microparticles (HMPs) for ROS scavenging and osteochondral regeneration has been developed. The prepared bioscaffold with multi-mimetic enzyme effects, which can scavenge a broad spectrum of free radicals in OA, can protect chondrocytes under the ROS microenvironment. Importantly, the bioscaffold can distinctly stimulate the proliferation and maturation of chondrocytes due to the stimulation of the glucose transporter pathway (GLUT) via HNPs/HMPs. Furthermore, it significantly accelerated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo results showed that the bioscaffold can effectively enhance the osteochondral regeneration compared to the unmodified scaffold. The work shows that integration of antioxidant and mechanical properties via the bioscaffold is a promising strategy for osteochondral regeneration in OA treatment.

Sprayable ß-FeSi2 composite hydrogel for portable skin tumor treatment and wound healing.

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, ß-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 ß-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.

3D Printing of Black Bioceramic Scaffolds with Micro/Nanostructure for Bone Tumor-Induced Tissue Therapy.

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.

3D Printed Wesselsite Nanosheets Functionalized Scaffold Facilitates NIR-II Photothermal Therapy and Vascularized Bone Regeneration.

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 [SrCuSi4 O10 ] 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.

3D-printed bioceramic scaffolds with Fe3S4microflowers for magnetothermal and chemodynamic therapy of bone tumor and regeneration of bone defects.

Elimination of residual osteosarcoma cells and repair of bone defects remain major challenges for osteosarcoma in clinic. To address this problem, it is required that multifunctional therapeutic platform possess high tumor-killing efficiency and simultaneous bone regeneration capabilities. In this work, an intelligent therapeutic platform was developed to achieve highly-efficient tumor therapy and simultaneous significantly improved bone defect repairing ability, which was realized byin situgrowing ferromagnetic Fe3S4layers with tuned microstructures on the surface of 3D-printed akermanite bioceramic scaffolds via hydrothermal method. The Fe3S4layers exploited magnetic thermal energy to enhance chemodynamic treatment, thus achieving a synergistic effect between magnetothermal and chemodynamic therapy on the elimination of residual tumor cells. Moreover, the micro-structured surface of the 3D-printed bioceramic scaffolds further enhanced the osteogenic activityin vitroand accelerated the bone regenerationin vivo. The scaffolds with multi-mode tumor-killing and bone repairing capabilities indicated that such a therapeutic platform is applicable for a stepwise treatment strategy of osteosarcoma and provides inspiration for the design of multifunctional biomaterials.

Manganese silicate nanospheres-incorporated hydrogels：starvation therapy and tissue regeneration.

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.

Manganese-Doped Calcium Silicate Nanowire Composite Hydrogels for Melanoma Treatment and Wound Healing.

Melanoma is a serious malignant skin tumor. Effectively eliminating melanoma and healing after-surgical wounds are always challenges in clinical studies. To address these problems, we propose manganese-doped calcium silicate nanowire-incorporated alginate hydrogels (named MCSA hydrogels) for in situ photothermal ablation of melanoma followed by the wound healing process. The proposed MCSA hydrogel had controllable gelation properties, reasonable strength, and excellent bioactivity due to the incorporated calcium silicate nanowires as the in situ cross-linking agents and bioactive components. The doping of manganese into calcium silicate nanowires gave them excellent photothermal effects for eradicating melanoma effectively under near infrared (NIR) irradiation. Moreover, the synergistic effect of manganese and silicon in the MCSA hydrogel effectively promotes migration and proliferation of vascular endothelial cells and promotes angiogenesis. Hence, such bifunctional bioactive hydrogels could achieve combined functions of photothermal therapy and wound healing, showing great promise for melanoma therapy and tissue regeneration.

Bone cements for therapy and regeneration for minimally invasive treatment of neoplastic bone defects.

Although calcium phosphate cements (CPCs) have been clinically used to repair bone defects caused by bone tumor resection, traditional CPCs cannot kill the remaining tumor cells after surgery and prevent cancer recurrence. In this study, a multifunctional injectable metal-organic framework (MOF) cobalt coordinated tetrakis(4-carboxyphenyl)porphyrin (Co-TCPP)-modified calcium phosphate cement (Co-TCPP/CPC) was prepared for the minimally invasive treatment of neoplastic bone defects. The incorporation of Co-TCPP not only retained the good injectability of bone cements, but also shortened the setting time, improved the compressive strength, and endowed them with excellent photothermal properties. The hyperthermia effect induced by the presence of Co-TCPP well induced the therapeutic effect against bone tumors both in vitro and in vivo. Moreover, Co-TCPP/CPC exhibited desirable osteogenesis and angiogenesis by promoting bone and vascular regeneration in vivo. Therefore, the Co-TCPP composite bone cement demonstrated its great potential for bone tumor therapy and tissue regeneration, representing a multifunctional biomaterial for the treatment of neoplastic bone defects.

Black Bioceramics: Combining Regeneration with Therapy.

Bioceramics have been developed from bioinert to bioactive or biodegradable materials in the past few decades. However, at present, traditional bioceramics are still mainly used in bone tissue regeneration and dental restoration. In this work, a new generation of "black bioceramics," extending the applications from tissue regeneration to disease therapy, is presented. Black bioceramics, through magnesium thermal reduction of traditional white ceramics, including silicate-based (e.g., CaSiO3 , MgSiO3 ) and phosphate-based (e.g., Ca3 (PO4 )2 , Ca5 (PO4 )3 (OH)), are successfully synthesized. Due to the presence of oxygen vacancies and structural defects, the black bioceramics possess photothermal functionality while maintaining their initial high bioactivity and regenerative capacity. These black bioceramics show excellent photothermal antitumor effects for both skin and bone tumors. At the same time, they have significantly improved bioactivity for skin/bone tissue repair in vitro and in vivo. These fascinating properties award the black bioceramics with profound applications in both tumor therapy and tissue regeneration, which should greatly promote the scientific relevance and clinical application of bioceramics, representing a promising new direction of cell-instructive biomaterials.