The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb2C MXene wrapped with S‐nitrosothiol (RSNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.

Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor, but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site. In this work, we report a rational integration of photonic-responsive two-dimensional (2D) ultrathin niobium carbide (Nb2C) MXene nanosheets (NSs) into the 3D-printed bone-mimetic scaffolds (NBGS) for osteosarcoma treatment. The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared (NIR-II) biowindow with high tissue-penetrating depth, making it highly efficient in killing bone cancer cells. Importantly, Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site, which can transport more oxygen, vitamins and energy around the bone defect for the reparative process, and gather more immune cells around the defect site to accelerate the degradation of NBGS. The degradation of NBGS provides sufficient space for the bone remodeling. Besides, calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue. The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXene-integrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.

Malignant bone tumors are one of the major serious diseases in clinic. Inferior reconstruction of new bone and rapid propagation of residual tumor cells are the main challenges to surgical intervention. Herein, a bifunctional DTC@BG scaffold for near‐infrared (NIR)‐activated photonic thermal ablation of osteosarcoma and accelerated bone defect regeneration is engineered by in situ growth of NIR‐absorbing cocrystal (DTC) on the surface of a 3D‐printing bioactive glass (BG) scaffold. The prominent photothermal conversion performance and outstanding bone regeneration capability of DTC@BG scaffolds originate from the precise tailoring of the bandgap between the electron donors and acceptors of DTC and promote new bone growth performance of BG scaffolds. DTC@BG scaffolds not only significantly promote tumor cell ablation in vitro, but also effectively facilitate bone tumor suppression in vivo. In particular, DTC@BG scaffolds exhibit excellent capability in stimulating osteogenic differentiation and angiogenesis, and finally promote newborn bone formation in the bone defects. This research represents the first paradigm for ablating osteosarcoma and facilitating new bone formation through precise modulation of electron donors and acceptors in the cocrystal, which offers a new avenue to construct high‐efficiency therapeutic platforms based on cocrystal strategy for ablation of malignant bone tumor.

Hierarchically porous structures and bioactive compositions of artificial biomaterials play a positive role in bone defect healing and new bone regeneration. Herein, cerium oxide nanoparticles-modified bioglass (Ce-BG) scaffolds were firstly constructed by the incorporation of hollow mesoporous Ce-BG microspheres in CTS via a freeze-drying technology. The interconnected macropores in Ce-BG scaffolds facilitated the in-growth of bone cells/tissues from material surfaces into the interiors, while the hollow cores and mesopore shells in Ce-BG microspheres provides more active sites for bone mineralization. The cerium oxide nanoparticles in the scaffolds rapidly promoted the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs), as confirmed by the up-regulation of osteogenesis-related markers such as OCN, ALP and COL-1. The enhanced osteoinductivity of Ce-BG scaffolds was mainly related to the activated ERK pathway, and it was blocked by adding a selective ERK1/2 inhibitor (SCH772984). In vivo rat cranial defect models revealed that Ce-BG scaffolds accelerated collagen deposition, osteoblast formation and bone regeneration as compared to BG scaffolds. The exciting results demonstrated that the synergistic effects between hierarchically porous structures and cerium oxide nanoparticles contributed to osteogenic ability, and hollow mesoporous Ce-BG scaffolds would be a novel platform for bone regeneration.

Background Sweat glands (SGs) and hair follicles (HFs) are two important cutaneous appendages that play crucial roles in homeostatic maintenance and thermoregulation, and their interaction is involved in wound healing. SGs can be regenerated from mesenchymal stem cell-laden 3D bioprinted scaffolds, based on our previous studies, whereas regeneration of HFs could not be achieved in the same model. Due to the lack of an in vitro model, the underlying molecular mechanism of the interaction between SGs and HFs in regeneration could not be fully understood. The purpose of the present study was to establish an in vitro model of skin constructs with SGs and HFs and explore the interaction between these two appendages in regeneration. Methods To investigate the interaction effects between SGs and HFs during their regeneration processes, a combined model was created by seeding HF spheroids on 3D printed SG scaffolds. The interaction between SG scaffolds and HF spheroids was detected using RNA expression and immunofluorescence staining. The effects of microenvironmental cues on SG and HF regeneration were analysed by altering seed cell types and plantar dermis homogenate in the scaffold. Results According to this model, we overcame the difficulties in simultaneously inducing SG and HF regeneration and explored the interaction effects between SG scaffolds and HF spheroids. Surprisingly, HF spheroids promoted both SG and HF differentiation in SG scaffolds, while SG scaffolds promoted SG differentiation but had little effect on HF potency in HF spheroids. Specifically, microenvironmental factors (plantar dermis homogenate) in SG scaffolds effectively promoted SG and HF genesis in HF spheroids, no matter what the seed cell type in SG scaffolds was, and the promotion effects were persistent. Conclusions Our approach elucidated a new model for SG and HF formation in vitro and provided an applicable platform to investigate the interaction between SGs and HFs in vitro. This platform might facilitate 3D skin constructs with multiple appendages and unveil the spatiotemporal molecular program of multiple appendage regeneration.

Alcohol is considered a leading risk factor for osteopenia. Our previous research indicated that the Akt/GSK‐3β/β‐catenin pathway plays a critical role in the ethanol‐induced antiosteogenic effect in bone mesenchymal stem cells (BMSCs). PI3K/Akt is negatively regulated by the phosphatase and tensin homolog (PTEN) phosphatase. In this study, we found that ethanol increased PTEN expression in the BMSCs and bone tissue of ethanol‐treated Sprague–Dawley rats. PTEN upregulation impaired Akt recruitment to the plasma membrane and suppressed Akt phosphorylation at Ser473, thereby inhibiting Akt/GSK3β/β‐catenin signaling and the expression of COL1 and OCN in BMSCs in vitro and in vivo. The results of in vivo assays indicated that PTEN inhibition protected bone tissue against ethanol. Interestingly, our data revealed that following ethanol stimulation, PTEN and PTEN pseudogene 1 (PTENP1) mRNA expression was increased in a time‐dependent manner, resulting in an increased PTEN protein level. In addition, ethanol upregulated PTEN expression and decreased PTEN phosphorylation (p‐PTEN), indicating an increase in functional PTEN levels. In summary, the ethanol‐mediated transcriptional and post‐transcriptional regulation of PTEN impaired downstream Akt/GSK3β/β‐catenin signaling and BMSC osteogenic differentiation. Therefore, we propose that Akt/GSK3β/β‐catenin activation via PTEN inhibition may be a potential therapeutic approach for preventing the development of alcohol‐induced osteopenia.

Bone is one of the most sophisticated and dynamic tissues in the human body, and is characterized by its remarkable potential for regeneration. In most cases, bone has the capacity to be restored to its original form with homeostatic functionality after injury without any remaining scarring. Throughout the fascinating processes of bone regeneration, a plethora of cell lineages and signaling molecules, together with the extracellular matrix, are precisely regulated at multiple length and time scales. However, conditions, such as delayed unions (or nonunion) and critical-sized bone defects, represent thorny challenges for orthopedic surgeons. During recent decades, a variety of novel biomaterials have been designed to mimic the organic and inorganic structure of the bone microenvironment, which have tremendously promoted and accelerated bone healing throughout different stages of bone regeneration. Advances in tissue engineering endowed bone scaffolds with phenomenal osteoconductivity, osteoinductivity, vascularization and neurotization effects as well as alluring properties, such as antibacterial effects. According to the dimensional structure and functional mechanism, these biomaterials are categorized as zero-dimensional, one-dimensional, two-dimensional, three-dimensional, and four-dimensional biomaterials. In this review, we comprehensively summarized the astounding advances in emerging biomaterials for bone regeneration by categorizing them as zero-dimensional to four-dimensional biomaterials, which were further elucidated by typical examples. Hopefully, this review will provide some inspiration for the future design of biomaterials for bone tissue engineering. Graphical abstract

modulates inflammation via suppressing TLR4/NF-κB pathway and promotes bone formation to ameliorate glucocorticoidinduced osteonecrosis of the femoral head in rat. Phytotherapy