Therefore, we have successfully constructed the organic-inorganic thermo-responsive CS-L hydrogel system containing the dual-GFs and bioactive metal ions, which exhibited excellent angiogenic and osteogenic properties and results in the satisfied bone regeneration performance.

Photodynamic therapy (PDT) has become a promising cancer treatment approach with superior advantages. However, it remains a grand challenge to develop tumor microenvironment (TME)‐responsive photosensitizers (PSs) for tumor‐targeting precise PDT. Herein, the coupling Lactobacillus acidophilus (LA) probiotics with 2D CoCuMo layered‐double‐hydroxide (LDH) nanosheets (LA&LDH) is reported as a TME‐responsive platform for precise NIR‐II PDT. The CoCuMo‐LDH nanosheets loaded on LA can be transformed from crystalline into amorphous through etching by the LA‐metabolite‐enabled low pH and overexpressed glutathione. The TME‐induced in situ amorphization of CoCuMo‐LDH nanosheets can boost its photodynamic activity for singlet oxygen (1O2) generation under 1270 nm laser irradiation with relative 1O2 quantum yield of 1.06, which is the highest among previously reported NIR‐excited PSs. In vitro and in vivo assays prove that the LA&LDH can effectively achieve complete cell apoptosis and tumor eradication under 1270 nm laser irradiation. This study proves that the probiotics can be used as a tumor‐targeting platform for highly efficient precise NIR‐II PDT.

Although artificial bone repair scaffolds, such as titanium alloy, bioactive glass, and hydroxyapatite (HAp), have been widely used for treatment of large-size bone defects or serious bone destruction, they normally exhibit unsatisfied bone repair efficiency because of their weak osteogenic and angiogenesis performance as well as poor cell crawling and adhesion properties. Herein, the surface functionalization of MgAlEu-layered double hydroxide (MAE-LDH) nanosheets on porous HAp scaffolds is reported as a simple and effective strategy to prepare HAp/MAE-LDH scaffolds for enhanced bone regeneration. The surface functionalization of MAE-LDHs on the porous HAp scaffold can significantly improve its surface roughness, specific surface, and hydrophilicity, thus effectively boosting the cells adhesion and osteogenic differentiation. Importantly, the MAE-LDHs grown on HAp scaffolds enable the sustained release of Mg 2+ and Eu 3+ ions for efficient bone repair and vascular regeneration. In vitro experiments suggest that the HAp/MAE-LDH scaffold presents much enhanced osteogenesis and angiogenesis properties in comparison with the pristine HAp scaffold. In vivo assays further reveal that the new bone mass and mineral density of HAp/MAE-LDH scaffold increased by 3.18-and 2.21-fold, respectively, than that of pristine HAp scaffold. The transcriptome sequencing analysis reveals that the HAp/MAE-LDH scaffold can activate the Wnt/𝜷-catenin signaling pathway to promote the osteogenic and angiogenic abilities.

The prevalence of osteoarthritis (OA), a degenerative disorder of joints, has substantially increased in recent years. Its key pathogenic hallmarks include articular cartilage destruction, synovium inflammation, and bone remodeling. However, treatment outcomes are unsatisfactory. Until recently, common therapy methods, such as analgesic and anti-inflammatory treatments, were aimed to treat symptoms that cannot be radically cured. Mesenchymal stem cells (MSCs), i.e., mesoderm non-hematopoietic cells separated from bone marrow, adipose tissue, umbilical cord blood, etc., have been intensively explored as an emerging technique for the treatment of OA over the last few decades. According to existing research, MSCs may limit cartilage degradation in OA by interfering with cellular immunity and secreting a number of active chemicals. This study aimed to examine the potential mechanism of MSCs in the treatment of OA and conduct a thorough review of both preclinical and clinical data.

Osteonecrosis of the femoral head (ONFH) is a devastating and complicated disease with an unclear etiology. Femoral head-preserving surgeries have been devoted to delaying and hindering the collapse of the femoral head since their introduction in the last century. However, the isolated femoral head-preserving surgeries cannot prevent the natural progression of ONFH, and the combination of autogenous or allogeneic bone grafting often leads to many undesired complications. To tackle this dilemma, bone tissue engineering has been widely developed to compensate for the deficiencies of these surgeries. During the last decades, great progress has been made in ingenious bone tissue engineering for ONFH treatment. Herein, we comprehensively summarize the state-of-the-art progress made in bone tissue engineering for ONFH treatment. The definition, classification, etiology, diagnosis, and current treatments of ONFH are first described. Then, the recent progress in the development of various bone-repairing biomaterials, including bioceramics, natural polymers, synthetic polymers, and metals, for treating ONFH is presented. Thereafter, regenerative therapies for ONFH treatment are also discussed. Finally, we give some personal insights on the current challenges of these therapeutic strategies in the clinic and the future development of bone tissue engineering for ONFH treatment. K E Y WO R D S biomaterials, bone tissue engineering, osteonecrosis of the femoral head, regenerative therapy  Yixin Bian and Tingting Hu contributed equally to this work.

Bone diseases including bone defects, bone infections, osteoarthritis, and bone tumors seriously affect life quality of the patient and bring serious economic burdens to social health management, for which the current clinical treatments bear dissatisfactory therapeutic effects. Biomaterial‐based strategies have been widely applied in the treatment of orthopedic diseases but are still plagued by deficient bioreactivity. With the development of nanotechnology, layered double hydroxides (LDHs) with adjustable metal ion composition and alterable interlayer structure possessing charming physicochemical characteristics, versatile bioactive properties, and excellent drug loading and delivery capabilities arise widespread attention and have achieved considerable achievements for bone disease treatment in the last decade. However, to the authors' best knowledge, no review has comprehensively summarized the advances of LDHs in treating bone disease so far. Herein, the advantages of LDHs for orthopedic disorders treatment are outlined and the corresponding state‐of‐the‐art achievements are summarized for the first time. The potential of LDHs‐based nanocomposites for extended therapeutics for bone diseases is highlighted and perspectives for LDHs‐based scaffold design are proposed for facilitated clinical translation.

The meniscus is a semilunar fibrocartilage between the tibia and femur that is essential for the structural and functional integrity of the keen joint. In addition to pain and knee joint dysfunction, meniscus injuries can also lead to degenerative changes of the knee joint such as osteoarthritis, which further affect patient productivity and quality of life. However, with intrinsic avascular property, the tearing meniscus tends to be nonunion and the augmentation of post-injury meniscus repair has long time been a challenge. Stem cell-based therapy with potent regenerative properties has recently attracted much attention in repairing meniscus injuries, among which mesenchymal stem cells were most explored for their easy availability, trilineage differentiation potential, and immunomodulatory properties. Here, we summarize the advances and achievements in stem cell-based therapy for meniscus repair in the last 5 years. We also highlight the obstacles before their successful clinical translation and propose some perspectives for stem cell-based therapy in meniscus repair.

Our recent study demonstrated the critical role of the mesolimbic dopamine (DA) circuit and its brain-derived neurotropic factor (BDNF) signaling in mediating neuropathic pain. The present study aims to investigate the functional role of GABA-ergic inputs from the lateral hypothalamus to the ventral tegmental area (LHGABA→VTA) in regulating the mesolimbic DA circuit and its BDNF signaling underlying physiological and pathological pain. We demonstrated that optogenetic manipulation of the LHGABA→VTA projection bi-directionally regulated pain sensation in naïve male mice. Optogenetic inhibition of this projection generated an analgesic effect in mice with pathological pain induced by chronic constrictive injury (CCI) of the sciatic nerve and persistent inflammatory pain by Complete Freund's Adjuvant. Trans-synaptic viral tracing revealed a monosynaptic connection between LH GABA-ergic neurons and VTA GABA-ergic neurons. Functionally,in vivocalcium/neurotransmitter imaging showed an increased DA neuronal activity, decreased GABA-ergic neuronal activity in the VTA, and increased dopamine release in the NAc, in response to optogenetic activation of the LHGABA→VTA projection. Furthermore, repeated activation of the LHGABA→VTA projection was sufficient to increase the expression of mesolimbic BDNF protein, an effect seen in mice with neuropathic pain. Inhibition of this circuit induced a decrease in mesolimbic BDNF expression in CCI mice. Interestingly, the pain behaviors induced by activation of the LHGABA→VTA projection could be prevented by pretreatment with intra-NAc administration of ANA-12, a TrkB receptor antagonist. These results demonstrated that LHGABA→VTA projection regulated pain sensation by targeting local GABA-ergic interneurons to disinhibit the mesolimbic DA circuit and regulating accumbal BDNF release.Significance StatementThe mesolimbic dopamine (DA) system its brain-derived neurotropic factor (BDNF) signaling has been implicated in pain regulation, however, underlying mechanisms remain poorly understood. The lateral hypothalamus (LH) sends the different afferent fibers into and strongly influences function of mesolimbic DA system. Here, utilizing cell type- and projection-specific viral tracing, optogenetics, in vivo calcium and neurotransmitter imaging, our current study identified the LHGABA-VTA projection as a novel neural circuit for pain regulation, possibly by targeting the VTA GABA-ergic neurons to disinhibit mesolimbic pathway-specific DA release and BDNF signaling. This study provides a better understanding of the role of LH and the mesolimbic DA system in physiological and pathological pain.