Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies.

Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

Cross-species signaling pathways analysis inspire animal model selections for drug screening and target prediction in vascular aging diseases.

Age is a significant contributing factor to the occurrence and progression of cardiovascular disease (CVD). Pharmacological treatment can effectively alleviate CVD symptoms caused by aging. However, 90% of the drugs have failed in clinics because of the loss of drug effects or the occurrence of the side effects. One of the reasons is the disparity between animal models used and the actual physiological levels in humans. Therefore, we integrated multiple datasets from single-cell and bulk-seq RNA-sequencing data in rats, monkeys, and humans to identify genes and pathways with consistent/differential expression patterns across these three species. An approach called "Cross-species signaling pathway analysis" was developed to select suitable animal models for drug screening. The effectiveness of this method was validated through the analysis of the pharmacological predictions of four known anti-vascular aging drugs used in animal/clinical experiments. The effectiveness of drugs was consistently observed between the models and clinics when they targeted pathways with the same trend in our analysis. However, drugs might have exhibited adverse effects if they targeted pathways with opposite trends between the models and the clinics. Additionally, through our approach, we discovered four targets for anti-vascular aging drugs, which were consistent with their pharmaceutical effects in literatures, showing the value of this approach. In the end, software was established to facilitate the use of "Cross-species signaling pathway analysis." In sum, our study suggests utilizing bioinformatics analysis based on disease characteristics can help in choosing more appropriate animal models.

Full-color, time-valve controllable and Janus-type long-persistent luminescence from all-inorganic halide perovskites.

Long persistent luminescence (LPL) has gained considerable attention for the applications in decoration, emergency signage, information encryption and biomedicine. However, recently developed LPL materials - encompassing inorganics, organics and inorganic-organic hybrids - often display monochromatic afterglow with limited functionality. Furthermore, triplet exciton-based phosphors are prone to thermal quenching, significantly restricting their high emission efficiency. Here, we show a straightforward wet-chemistry approach for fabricating multimode LPL materials by introducing both anion (Br-) and cation (Sn2+) doping into hexagonal CsCdCl3 all-inorganic perovskites. This process involves establishing new trapping centers from [CdCl6-nBrn]4- and/or [Sn2-nCdnCl9]5- linker units, disrupting the local symmetry in the host framework. These halide perovskites demonstrate afterglow duration time ( > 2,000 s), nearly full-color coverage, high photoluminescence quantum yield ( ~ 84.47%), and the anti-thermal quenching temperature up to 377 K. Particularly, CsCdCl3:x%Br display temperature-dependent LPL and time-valve controllable time-dependent luminescence, while CsCdCl3:x%Sn exhibit forward and reverse excitation-dependent Janus-type luminescence. Combining both experimental and computational studies, this finding not only introduces a local-symmetry breaking strategy for simultaneously enhancing afterglow lifetime and efficiency, but also provides new insights into the multimode LPL materials with dynamic tunability for applications in luminescence, photonics, high-security anti-counterfeiting and information storage.

Burden evaluation and prediction of osteoarthritis and site-specific osteoarthritis coupled with attributable risk factors in China from 1990 to 2030.

OBJECTIVE: This study aimed to estimate and predict the burden of osteoarthritis (OA) and site-specific OA (hip, knee, hand, and others) from 1990 to 2030 and their attributable risk factors in China. METHOD: Data were obtained from the Global Burden of Diseases 2019. The burden was estimated by analyzing the trends of prevalence, incidence, and disability-adjusted life years (DALY). Population attributable risk (PAR) was calculated to assess the impact of high body mass index (BMI). The prediction from 2020 to 2030 was implemented by Bayesian age-period-cohort analysis. RESULTS: In China, prevalent cases, DALY, and incident cases of OA increased to 132.81 million, 4.72 million, and 10.68 million, respectively. Age-standardized rates (ASRs) of prevalence, DALYs, and incidence increased for OA and site-specific OA, especially for hip OA. Site-specific OA showed different susceptible peaking ages, and the burden for those over 50 years old became serious. Female preference existed in the trends for knee OA but not in those for hip, hand, and other OA. PARs of high BMI continued to increase, impacting knee OA more than hip OA and showing female preference. In the next decade, incident cases for OA and site-specific OA will continue to increase, despite that the ASR of OA incidence will decrease. CONCLUSIONS: OA and site-specific OA remain huge public health challenges in China. The burden of OA and site-specific OA is increasing, especially among people over 50 years old. Health education, exercise, and removing modifiable risk factors contribute to alleviate the growing burden. Key Points • In China, the burden of osteoarthritis and site-specific osteoarthritis (hip, knee, hand, and others) as well as the Risk Factor (high body mass index) increased greatly from 1990 to 2019. • It is estimated that incident cases for OA and site-specific OA will continue to increase, despite that the ASR of OA incidence will decrease.

A flexible ligand and halogen engineering enable one phosphor-based full-color persistent luminescence in hybrid perovskitoids.

Color-tunable room temperature phosphorescent (RTP) materials have raised wide interest due to their potential application in the fields of encryption and anti-counterfeiting. Herein, a series of CdX2-organic hybrid perovskitoids, (H-apim)CdX3 and (apim)CdX2 (denoted as CdX-apim1 and CdX-apim2, apim = 1-(3-aminopropyl)imidazole, X = Cl, Br), were synthesized using apim with both rigid and flexible groups as ligands, which exhibit naked-eye detectable RTP with different durations and colors (from cyan to red) by virtue of different halogen atoms, coordination modes and the coplanar configuration of flexible groups. Interestingly, CdCl-apim1 and CdX-apim2 both exhibit excitation wavelength-dependent RTP properties, which can be attributed to the multiple excitation of imidazole/apim, the diverse interactions with halogen atoms, and aggregated state of imidazoles. Structural analysis and theoretical calculations confirm that the aminopropyl groups in CdCl-apim1 do not participate in luminescence, while those in CdCl-apim2 are involved in luminescence including both metal/halogen to ligand charge transfer and twisted intramolecular charge transfer. Furthermore, we demonstrate that these perovskitoids can be applied in multi-step anti-counterfeiting, information encryption and smart ink fields. This work not only develops a new type of perovskitoid with full-color persistent luminescence, but also provides new insight into the effect of flexible ligands and halogen engineering on the wide-range modulation of RTP properties.

A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration.

Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-Ⅰ via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-Ⅰ to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-Ⅰ nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.

Bioprinted vascular tissue: Assessing functions from cellular, tissue to organ levels.

3D bioprinting technology is widely used to fabricate various tissue structures. However, the absence of vessels hampers the ability of bioprinted tissues to receive oxygen and nutrients as well as to remove wastes, leading to a significant reduction in their survival rate. Despite the advancements in bioinks and bioprinting technologies, bioprinted vascular structures continue to be unsuitable for transplantation compared to natural blood vessels. In addition, a complete assessment index system for evaluating the structure and function of bioprinted vessels in vitro has not yet been established. Therefore, in this review, we firstly highlight the significance of selecting suitable bioinks and bioprinting techniques as they two synergize with each other. Subsequently, focusing on both vascular-associated cells and vascular tissues, we provide a relatively thorough assessment of the functions of bioprinted vascular tissue based on the physiological functions that natural blood vessels possess. We end with a review of the applications of vascular models, such as vessel-on-a-chip, in simulating pathological processes and conducting drug screening at the organ level. We believe that the development of fully functional blood vessels will soon make great contributions to tissue engineering and regenerative medicine.

A Novel PTH-Related Peptide Combined With 3D Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration.

Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTASP2 ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTASP2 exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.

Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer.

Immune checkpoint inhibitors (ICIs) target the negative regulatory pathway of T cells and effectively reactive the anti-tumor immune function of T cells by blocking the key pathway of the immune escape mechanism of the tumor-PD-1/PD-L1, and fundamentally changing the prospect of immunotherapy for non-small cell lung cancer patients. However, such promising immunotherapy is overshadowed by Hyperprogressive Disease, a response pattern associated with unwanted accelerated tumor growth and characterized by poor prognosis in a fraction of treated patients. This review comprehensively provides an overview of Hyperprogressive Disease in immune checkpoint inhibitor-based immunotherapy for non-small cell lung cancer including its definition, biomarkers, mechanisms, and treatment. A better understanding of the black side of immune checkpoint inhibitors therapy will provide a more profound insight into the pros and cons of immunotherapy.

Enhanced Transport and Optoelectronic Properties of van der Waals Materials on CaF2 Films.

To achieve better properties of van der Waals (vdW) devices, vdW heterointerfaces with substrates such as hexagonal boron nitride (h-BN) were introduced to alleviate adverse substrate effects. However, the premature dielectric breakdown and its scale limitation make wider application of h-BN substrates challenging. Here we report a fluoride-based substrate that substantially improves optoelectronic and transport properties of dichalcogenide devices, with enhancement factors comparable to those of h-BN. A model system of wafer-scale fluoride calcium (CaF2) ultrathin films with the preferable growth direction along [111] is prepared by the magnetron sputtering method. Results show that the constructed SnS2/CaF2 and WS2/CaF2 devices exhibit 1 order of magnitude higher than devices based on the SiO2 substrate in electronic mobility and photoresponsivity. Theoretical calculations reveal that devices based on fluoride substrates are immune from the Coulomb impurity scattering by forming quasi-vdW interfaces, exhibiting great potential for high responsivity and mobility of photogenerated carriers in 2D vdW devices.

Zn-Sr-sintered true bone ceramics enhance bone repair and regeneration.

Bone defects are one of the toughest challenges faced by orthopedic surgeons worldwide, especially at critical sizes, which are caused by severe trauma, malignancy, or congenital disease. The ideal bone tissue-engineered scaffold for bone regeneration is the one that has good osteoconductivity, osteoinductivity, pore structure, and antibacterial properties. Metal ions have been recognized in recent years to be essential regulators of bone metabolism, and they are widely used for bone tissue engineering. In particular, zinc ions are of interest because of their ideal biocompatibility, osteogenesis-promoting properties, and antibacterial properties. Moreover, the dual role of strontium (Sr) in promoting osteogenesis and inhibiting osteolysis provides academic support for Zn-Sr co-doped scaffolds. Based on true bone ceramics (TBC), Zn-Sr-sintered scaffolds with good pore structures were prepared using immersion-calcination. The biocompatibility, cell adhesion, osteogenic properties, and antibacterial activity of Zn-Sr-sintered TBC scaffolds in bone marrow mesenchymal stem cells (BMSCs) are superior to those of control TBC scaffolds. The Zn-Sr-sintered TBC scaffold was used to repair rat cranial defects. Its good in vivo repair performance was confirmed by osseointegration and inward bone growth compared with that of the control TBC scaffold. Zn0.25Sr0.20-TBC is an ideal material for bone repair because of its good biocompatibility and favorable in vitro osteogenic properties.

"Smart" Stimuli-responsive Injectable Gels for Bone Tissue Engineering Application.

Bone grafting, as the current gold-standard for large scaled bone damage of various causes, has faced challenges from both the source and appliance. Emerging new tissue engineering substitutes are demonstrating more options and possibilities, with their improved biocompatibility, accessibility, and customizable function. Amongst them, injectable gels (IGs) are a class of gel material displaying astonishing non-invasive properties and surgical viability. While possessing responsiveness toward specific stimuli, they change their physical form in vivo, thus serving as wonderful biomaterials and drug delivery systems. In this review, the mechanics of stimuli-responsive IGs developed during the past decade are illustrated. Two branches of crosslinked gels - co-valent and non-covalent crosslinked IGs and their composition and customization are introduced. In conclusion, the present trend in bone tissue engineering research is summarized and made an outlook for future. It is hoped that this comprehensive review can provide a proper reference for the development of new IGs.

Leveraging Crystalline and Amorphous States of a Metal-Organic Complex for Transformation of the Photosalient Effect and Positive-Negative Photochromism.

Uncovering differences between crystalline and amorphous states in molecular solids would both promote the understanding of their structure-property relationships, as well as inform development of multi-functional materials based on the same compound. Herein, for the first time, we report an approach to leverage crystalline and amorphous states of a zero-dimensional metal-organic complex, which exhibited negative and positive photochromism, due to the competitive chemical routes between photocycloaddition and photogenerated radicals. Furthermore, different polymorphs lead to the on/off toggling of photo-burst movement (photosalient effect), indicating the controllable light-mechanical conversion. Three demos were further constructed to support their application in information encryption and anti-counterfeiting. This work provides the proof-of-concept of a state- and polymorph-dependent photochemical route, paving an effective way for the design of new dynamically responsive systems.

Antimicrobial peptides for bone tissue engineering: Diversity, effects and applications.

Bone tissue engineering has been becoming a promising strategy for surgical bone repair, but the risk of infection during trauma repair remains a problematic health concern worldwide, especially for fracture and infection-caused bone defects. Conventional antibiotics fail to effectively prevent or treat bone infections during bone defect repair because of drug-resistance and recurrence, so novel antibacterial agents with limited resistance are highly needed for bone tissue engineering. Antimicrobial peptides (AMPs) characterized by cationic, hydrophobic and amphipathic properties show great promise to be used as next-generation antibiotics which rarely induce resistance and show potent antibacterial efficacy. In this review, four common structures of AMPs (helix-based, sheet-based, coil-based and composite) and related modifications are presented to identify AMPs and design novel analogs. Then, potential effects of AMPs for bone infection during bone repair are explored, including bactericidal activity, anti-biofilm, immunomodulation and regenerative properties. Moreover, we present distinctive applications of AMPs for topical bone repair, which can be either used by delivery system (surface immobilization, nanoparticles and hydrogels) or used in gene therapy. Finally, future prospects and ongoing challenges are discussed.

Ultrasensitive multiplexed chemiluminescent enzyme-linked immunosorbent assays in 384-well plates.

We have developed an ultrasensitive multiplexed immunoassay using 384-well microtiter plates capable of detecting proteins at subfemtomolar concentrations that requires as little as 2.5 µL of sample. Arrays of up to 4 capture antibodies were patterned on the bottom of the wells of a 384-well plate either by directly printing the capture antibodies or by printing anti-peptide tag anchor antibodies and incubating these arrays with capture antibodies conjugated to the corresponding peptide tags ("customized" assays). Samples were incubated with the antibody arrays and shaken orbitally at 2000 rpm to achieve the greatest sensitivity. Chemiluminescence (CL) from immunocomplexes labeled with horseradish peroxidase was imaged across the entire plate to quantify the amount of protein bound to each antibody spot of the arrays. The 384-well assay had a throughput 5-fold greater than 96-well plates that was achieved from simultaneous imaging of CL in all 384-wells and the use of automated pipettors to allow parallel processing of 384 assays. We developed 4 assays based on the 384-well CL ELISA: a direct print assay for IL-10 (limit of detection (LOD) = 0.075 fM); a customized assay for IL-6 (0.22 fM); a customized pharmacokinetic (PK) assay for measuring adalimumab (7.3 pg/mL); and a customized 4-plex assay for IL-5 (0.1 fM), IL-6 (0.52 fM), IL-10 (0.2 fM), and TNF-α (3.2 fM). The sensitivity and precision of the cytokine assays were comparable to current ultrasensitive protein detection methods in 96-well formats. The PK assay for adalimumab was 650 times more sensitive than a commercially available 96-well plate ELISA. We used the 384-well CL ELISAs to measure endogenous levels of the cytokines in the serum and plasma of healthy humans: the mean concentrations and precision were comparable to those from 96-well immunoassays. This 384-well format with subfemtomolar sensitivity will enable ultrasensitive multiplexed immunoassays to be performed with higher throughput and lower sample volumes than currently possible, a particularly important capability for clinical studies in drug development.

A molecular recognition platform for the simultaneous sensing of diverse chemical weapons.

Chemical warfare agents (CWAs) such as phosgene and nerve agents pose serious threats to our lives and public security, but no tools can simultaneously screen multiple CWAs in seconds. Here, we rationally designed a robust sensing platform based on 8-cyclohexanyldiamino-BODIPY (BODIPY-DCH) to monitor diverse CWAs in different emission channels. Trans-cyclohexanyldiamine as the reactive site provides optimal geometry and high reactivity, allowing trans-BODIPY-DCH to detect CWAs with a quick response and high sensitivity, while cis-BODIPY-DCH has much weaker reactivity to CWAs due to intramolecular H-bonding. Upon reaction with phosgene, trans-BODIPY-DCH was rapidly converted to imidazolone BODIPY (<3 s), triggering green fluorescence with good sensitivity (LOD = 0.52 nM). trans-BODIPY-DCH coupled with nerve agent mimics, affording a blue fluorescent 8-amino-BODIPY tautomer. Furthermore, a portable test kit using trans-BODIPY-DCH displayed an instant response and low detection limits for multiple CWAs. This platform enables rapid and highly sensitive visual screening of various CWAs.

Fungicidal properties of ginger (Zingiber officinale) essential oils against Phytophthora colocasiae.

Recently, plant essential oils (EOs) have attracted special attention in plant disease control and food preservation. Since ancient times, essential oils extracted from plants have exhibited many biological characteristics, especially antimicrobial properties. Recent studies have described the potentials of EOs and derivatives to inhibit the growth and reproduction of microorganisms, mainly in response of overwhelming concerns of consumers about food safety. In the context of returning to nature, with the advancement of science and technology and improved living standards, people have begun to seek solutions for food hygiene without chemical additives. Therefore, biological pesticides and plant-oriented chemicals have received special attention from scientists because they are environmentally friendly and nonhazardous, sustainable, and effective alternatives against many noxious phytopathogens. Present study is intended to appraise the fungicidal properties of ginger EOs to combat leaf blight disease of taro, which threatens global taro production. Farmers often hinge on extremely toxic synthetic fungicides to manage diseases, but the residual effects and resistance of chemicals are unavoidable. The microwave-assisted hydrodistillation method was used for ginger EOs extraction and an FTIR (ATR) spectrometer was used to evaluate their chemical composition and citral was identified as most abundant compound (89.05%) in oil. The pathogen isolated from lesions of diseased taro plants was identified as Phytophthora colocasiae and used as test fungus in the present study. Ginger EO was evaluated in-vitro for antifungal properties against mycelium growth, sporangium production, zoospore germination, leaf, and corm necrosis inhibition. Repeated experiments have shown that the concentration of ginger essential oil (1250 ppm) proved to be the lowest dose to obtain 100% inhibition of fungal growth and spore germination, sporangia formation and leaf necrosis assessment. These results are derived from this fungal species and a hypothesis that involves further research on other plant pathogens to demonstrate the overall potency of essential oils. This study references the easy, economic, and environmental management and control of plant diseases using essential oils and byproducts.

Supramolecular Peptide Nanofiber Hydrogels for Bone Tissue Engineering: From Multihierarchical Fabrications to Comprehensive Applications.

Bone tissue engineering is becoming an ideal strategy to replace autologous bone grafts for surgical bone repair, but the multihierarchical complexity of natural bone is still difficult to emulate due to the lack of suitable biomaterials. Supramolecular peptide nanofiber hydrogels (SPNHs) are emerging biomaterials because of their inherent biocompatibility, satisfied biodegradability, high purity, facile functionalization, and tunable mechanical properties. This review initially focuses on the multihierarchical fabrications by SPNHs to emulate natural bony extracellular matrix. Structurally, supramolecular peptides based on distinctive building blocks can assemble into nanofiber hydrogels, which can be used as nanomorphology-mimetic scaffolds for tissue engineering. Biochemically, bioactive motifs and bioactive factors can be covalently tethered or physically absorbed to SPNHs to endow various functions depending on physiological and pharmacological requirements. Mechanically, four strategies are summarized to optimize the biophysical microenvironment of SPNHs for bone regeneration. Furthermore, comprehensive applications about SPNHs for bone tissue engineering are reviewed. The biomaterials can be directly used in the form of injectable hydrogels or composite nanoscaffolds, or they can be used to construct engineered bone grafts by bioprinting or bioreactors. Finally, continuing challenges and outlook are discussed.

Mesenchymal Stem Cell-Immune Cell Interaction and Related Modulations for Bone Tissue Engineering.

Critical bone defects and related delayed union and nonunion are still worldwide problems to be solved. Bone tissue engineering is mainly aimed at achieving satisfactory bone reconstruction. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells that can differentiate into bone cells and can be used as one of the key pillars of bone tissue engineering. In recent decades, immune responses play an important role in bone regeneration. Innate immune responses provide a suitable inflammatory microenvironment for bone regeneration and initiate bone regeneration in the early stage of fracture repair. Adaptive immune responses maintain bone regeneration and bone remodeling. MSCs and immune cells regulate each other. All kinds of immune cells and secreted cytokines can regulate the migration, proliferation, and osteogenic differentiation of MSCs, which have a strong immunomodulatory ability to these immune cells. This review mainly introduces the interaction between MSCs and immune cells on bone regeneration and its potential mechanism, and discusses the practical application in bone tissue engineering by modulating this kind of cell-to-cell crosstalk. Thus, an in-depth understanding of these principles of bone immunology can provide a new way for bone tissue engineering.