Enhancing Methane Gas Sensing through Defect Engineering in Ag-Ru Co-doped ZnO Nanorods.

Detection of leaks of flammable methane (CH4) gas in a timely manner can mitigate health, safety, and environmental risks. Zinc oxide (ZnO), a polar semiconductor with controllable surface defects, is a promising material for gas sensing. In this study, Ag-Ru co-doped into self-assembled ZnO nanorod arrays (ZnO NRs) was prepared by a one-step hydrothermal method. The Ag-Ru co-doped sample shows a good hydrophobic property as a result of its particular microstructure, which results in high humidity resistance. In addition, oxygen vacancy density significantly increased after Ag-Ru co-doping. Density functional theory (DFT) calculations revealed an exceptionally high charge density accumulated at the Ru sites and the formation of a localized strong electric field, which provides additional energy for the CH4 reaction with •O2- at the surface at room temperature. Optimized AgRu0.025-ZnO demonstrated an outstanding CH4 sensing performance, with a limit of detection (LOD) as low as 2.24 ppm under free-heat and free-light conditions. These findings suggest that introducing defects into the ZnO lattice, such as oxygen vacancies and localized ions, offers a promising approach to improving the gas sensing performance.

Artificial periosteum promotes bone regeneration through synergistic immune regulation of aligned fibers and BMSC-recruiting phages.

Given the crucial role of periosteum in bone repair, the use of artificial periosteum to induce spontaneous bone healing instead of using bone substitutes has become a potential strategy. Also, the proper transition from pro-inflammatory signals to anti-inflammatory signals is pivotal for achieving optimal repair outcomes. Hence, we designed an artificial periosteum loaded with a filamentous bacteriophage clone named P11, featuring an aligned fiber morphology. P11 endowed the artificial periosteum with the capacity to recruit bone marrow mesenchymal stem cells (BMSCs). The artificial periosteum also regulated the immune microenvironment at the bone injury site through the synergistic effects of biochemical factors and topography. Specifically, the inclusion of P11 preserved inflammatory signaling in macrophages and additionally facilitated the migration of BMSCs. Subsequently, aligned fibers stimulated macrophages, inducing alterations in cytoskeletal and metabolic activities, resulting in the polarization into the M2 phenotype. This progression encouraged the osteogenic differentiation of BMSCs and promoted vascularization. In vivo experiments showed that the new bone generated in the AP group exhibited the most efficient healing pattern. Overall, the integration of biochemical factors with topographical considerations for sequential immunomodulation during bone repair indicates a promising approach for artificial periosteum development. STATEMENT OF SIGNIFICANCE: The appropriate transition of macrophages from a pro-inflammatory to an anti-inflammatory phenotype is pivotal for achieving optimal bone repair outcomes. Hence, we designed an artificial periosteum featuring an aligned fiber morphology and loaded with specific phage clones. The artificial periosteum not only fostered the recruitment of BMSCs but also achieved sequential regulation of the immune microenvironment through the synergistic effects of biochemical factors and topography, and improved the effect of bone repair. This study indicates that the integration of biochemical factors with topographical considerations for sequential immunomodulation during bone repair is a promising approach for artificial periosteum development.

Postoperatively Noninvasive Optogenetic Stimulation via Upconversion Nanoparticles Enhancing Sciatic Nerve Repair.

The efficacy of electrical stimulation facilitating peripheral nerve regeneration is evidenced extensively, while the associated secondary damage resulting from repeated electrode invasion and indiscriminate stimulation is inevitable. Here, we present an optogenetics strategy that utilizes upconversion nanoparticles (UCNPs) to convert deeply penetrating near-infrared excitation into blue emission, which activates an adeno-associated virus-encoding ChR2 photoresponsive ion channel on cell membranes. The induced Ca2+ flux, similar to the ion flux in the electrical stimulation approach, efficiently regulates viability and proliferation, secretion of nerve growth factor, and neural function of RSC96 cells. Furthermore, deep near-infrared excitation is harnessed to stimulate autologous Schwann cells in situ via a UCNP-composited scaffold, which enhances nerve sprouting and myelination, consequently promoting functional recovery, electrophysiological restoration, and reinnervation of damaged nerves. This developed postoperatively noninvasive optogenetics strategy presents a novel, minimally traumatic, and enduring therapeutic stimulus to effectively promote peripheral nerve repair.

Ratiometric fluorescence detection of dopamine based on copper nanoclusters and carbon dots.

Nanoclusters for fluorescence detection are generally comprised of rare and expensive noble metals, and the nanoclusters based on more affordable transition metal have attracted increasing attention. This study designed a ratiometric fluorescent probe to detect dopamine (DA), an important neurotransmitter. With carbon dots encapsulated within silica (CDs@SiO2) as the reference, the emitted reference signal was almost unchanged due to the protection of inert silicon shell. Meanwhile, copper nanoclusters modified with 3-aminophenyl boronic acid (APBA-GSH-CuNCs) provided the sensing signal, in which the phenylboric acid could specifically recognize the cis-diol structure of DA, and caused the fluorescence quenching by photoinduced electron transfer. This dual emission ratiometric fluorescent probe exhibited high sensitivity and anti-interference, and was able to selectively responded to DA with a linear range of 0-1.4 mM, the detection limit of 5.6 nM, and the sensitivity of 815 mM-1. Furthermore, the probe successfully detected DA in human serum samples, yielding recoveries ranging from 92.5% to 102.7%. Overall, this study highlights the promising potential of this ratiometric probe for detecting DA.

Progress and mechanism of graphene oxide-composited materials in application of peripheral nerve repair.

Peripheral nerve injuries (PNI) are one of the most common nerve injuries, and graphene oxide (GO) has demonstrated significant potential in the treatment of PNI. GO could enhance the proliferation, adhesion, migration, and differentiation of neuronal cells by upregulating the expression of relevant proteins, and regulate the angiogenesis process and immune response. Therefore, GO is a suitable additional component for fabricating artificial nerve scaffolds (ANS), in which the slight addition of GO could improve the physicochemical performance of the matrix materials, through hydrogen bonds and electrostatic attraction. GO-composited ANS can increase the expression of nerve regeneration-associated genes and factors, promoting angiogenesis by activating the RAS/MAPK and AKT-eNOS-VEGF signaling pathway, respectively. Moreover, GO could be metabolized and excreted from the body through the pathway of peroxidase degradation in vivo. Consequently, the application of GO in PNI regeneration exhibits significant potential for transitioning from laboratory research to clinical use.

Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs.

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.

H2S-Reactivating Antitumor Immune Response after Microwave Thermal Therapy for Long-Term Tumor Suppression.

Microwave thermal therapy (MWTT) is one of the most potent ablative treatments known, with advantages like deep penetration, minimal invasion, repeatable operation, and low interference from bone and gas. However, microwave (MW) is not selective against tumors, and residual tumors after incomplete ablation will generate immunosuppression, ultimately making tumors prone to recurrence and metastasis. Herein, a nano-immunomodulator (Bi-MOF-l-Cys@PEG@HA, BMCPH) is proposed to reverse the immunosuppression and reactivate the antitumor immune effect through responsively releasing H2S in tumor cells for improving MWTT. Under MW irradiation, BMCPH will mediate MWTT to ablate tumors and release l-cysteine (l-Cys) to react with the highly expressed cystathionine ß-synthase in tumor to generate H2S. The generated H2S can inhibit the accumulation of myeloid-derived suppressor cells (MDSCs) and promote the expression of cytotoxic T lymphocytes (CTLs). Moreover, Bi-MOF can also scavenge reactive oxygen species (ROS), a major means of MDSCs-mediated immunosuppression, to further weaken the immunosuppressive effect. Simultaneously, the surface-covered HA will gather CTLs around the tumor to enhance the immune response. This nano gas immunomodulator provides an idea for the sensitive and tunable release of unstable gas molecules at tumor sites. The strategy of H2S gas to reverse immunosuppression and reactivate antitumor immune response introduces a direction to reduce the risk of tumor recurrence and metastasis after thermal ablation.

Vanadium-Doped Mesoporous Bioactive Glass Promotes Osteogenic Differentiation of rBMSCs via the WNT/ß-Catenin Signaling Pathway.

Pentavalent vanadium [V(V)] has been studied as bioactive ions to improve the bone defect repair; however, its osteogenic promotion mechanism is still not fully understood so far. In this study, a V-doped mesoporous bioactive glass (V-MBG) was prepared, and its effects on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and potential signaling pathways were investigated. The physicochemical characterization revealed that the incorporation of V slightly reduced the specific surface area and increased the mesoporous pore size, and the abundant mesopores of V-MBG were beneficial to the sustained dissolution of V(V) ions as well as calcium, silicon, and phosphorus ions. Cell proliferation results indicated that the high dilution ratio (>16) V-MBG extract markedly promoted the proliferation of rBMSCs compared with the control group and the same dilution ratio MBG extract. Compared with the same dilution ratio MBG extract, diluted V-MBG extracts markedly promoted the secretion of alkaline phosphatase (ALP) and osteocalcin (OCN) protein at day 7 but insignificantly stimulated the runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF) protein synthesis. In depth, the diluted V-MBG extracts remarkably up-regulated the expression of WNT/ß-catenin pathway direct target genes, including WNT3a, ß-catenin, and AXIN2 genes in contrast to the same dilution ratio MBG extracts, suggesting that the released V(V) ions might promote osteogenic differentiation of rBMSCs via the WNT/ß-catenin signaling pathway.

Unique Chirality Selection in Neural Cells for D-Matrix Enabling Specific Manipulation of Cell Behaviors.

Manipulating neural cell behaviors is a critical issue to various therapies for neurological diseases and damages, where matrix chirality has long been overlooked despite the proven adhesion and proliferation improvement of multiple non-neural cells by L-matrixes. Here, it is reported that the D-matrix chirality specifically enhances cell density, viability, proliferation, and survival in four different types of neural cells, contrasting its inhibition in non-neural cells. This universal impact on neural cells is defined as "chirality selection for D-matrix" and is achieved through the activation of JNK and p38/MAPK signaling pathways by the cellular tension relaxation resulting from the weak interaction between D-matrix and cytoskeleton proteins, particularly actin. Also, D-matrix promotes sciatic nerve repair effectively, both with or without non-neural stem cell implantation, by improving the population, function, and myelination of autologous Schwann cells. D-matrix chirality, as a simple, safe, and effective microenvironment cue to specifically and universally manipulate neural cell behaviors, holds extensive application potential in addressing neurological issues such as nerve regeneration, neurodegenerative disease treatment, neural tumor targeting, and neurodevelopment.

Preparation of Janus fluorescent probe based on an asymmetrical silica and its application in glucose and alpha-fetoprotein detection.

Janus particles have been considered suitable for biomedicine owing to their asymmetric structure and unique properties. Although Janus particles have been applied in biosensing for dual-mode sensing, there are almost no reports for the detection of multiple indicators. In fact, many patients require different diagnoses, such as the examination of hepatogenic diseases in diabetics. Here, a Janus particle based on SiO2 was synthesized using a Pickering emulsion method. A novel strategy for detecting glucose and alpha-fetoprotein (AFP) based on different principles using this Janus particle was then constructed as a detection platform. Composed of adjustable dendritic silica loaded with gold nanoclusters (Au NCs) and glucose oxidase (GOx) and spherical SiO2 coupled with AFP antibody, this Janus fluorescent probe achieved the double detection of glucose and AFP. With the protection of dendritic silica, the enzyme temperature stability was enhanced. Moreover, the low limit of detection for glucose (0.5 µM in PBS and 2.5 µM in serum) and AFP (0.5 ng mL-1) illustrated the feasibility of the application of the Janus material in integrated detection. This work not only supported the use of a Janus fluorescent probe as a detection platform toward glucose and AFP but also showed the potential of Janus particles in integrated detection in the future.

Identification of a Specific Phage as Growth Factor Alternative Promoting the Recruitment and Differentiation of MSCs in Bone Tissue Regeneration.

Inefficient use and loss of exogenously implanted mesenchymal stem cells (MSCs) are major concerns in MSCs-based bone tissue engineering. It is a promising approach to overcome the above issues by recruiting and regulation of endogenous MSCs. However, there are few substances that can recruit MSCs effectively and specifically to the site of bone injury. In this study, we identified a phage clone (termed P11) with specific affinity for MSCs through phage display biopanning, and further investigated the effects of P11 on the cytological behavior of MSCs and macrophages. The results showed that P11 could bind MSCs specifically and promote the proliferation and migration of MSCs. Meanwhile, P11 could polarize macrophages to the M1 phenotype and significantly changed their morphology, which further enhanced the chemotaxis of MSCs. Additionally, RNA-seq results revealed that P11 could promote the secretion of osteogenesis-related markers in MSCs through the TPL2-MEK-ERK signaling pathway. Altogether, P11 has great potential to be used as growth factor alternatives in bone tissue engineering, with the advantages of cheaper and stable activity. Our study also advances the understanding of the effects of phages on macrophages and MSCs, and provides a new idea for the development in the field of phage-based tissue engineering.

Reversing the immunosuppressive microenvironment with reduced redox level by microwave-chemo-immunostimulant Ce-Mn MOF for improved immunotherapy.

BACKGROUNDS: Reversing the immunosuppressive tumor microenvironment (TME) in the tumor is widely deemed to be an effective strategy to improve immune therapy. In particular, the redox balance in TME needs to be well controlled due to its critical role in mediating the functions of various cells, including cancer cells and immune-suppressive cells. RESULTS: Here, we propose an efficient strategy to reshape the redox homeostasis to reverse immunosuppressive TME. Specifically, we developed a microwave-chemo-immunostimulant CMMCP to promote the infiltration of the tumor-T cells by simultaneously reducing the reactive oxygen species (ROS) and glutathione (GSH) and improving the oxygen (O2) levels in TME. The CMMCP was designed by loading chemotherapy drugs cisplatin into the bimetallic Ce-Mn MOF nanoparticles coated with polydopamine. The Ce-Mn MOF nanoparticles can effectively improve the catalytic decomposition of ROS into O2 under microwave irradiation, resulting in overcoming hypoxia and limited ROS generation. Besides, the activity of intracellular GSH in TME was reduced by the redox reaction with Ce-Mn MOF nanoparticles. The reprogrammed TME not only boosts the immunogenic cell death (ICD) induced by cisplatin and microwave hyperthermia but also gives rise to the polarization of pro-tumor M2-type macrophages to the anti-tumor M1-type ones. CONCLUSION: Our in vivo experimental results demonstrate that the microwave-chemo-immunostimulant CMMCP significantly enhances the T cell infiltration and thus improves the antitumor effect. This study presents an easy, safe, and effective strategy for a whole-body antitumor effect after local treatment.

Combined photothermal-photodynamic therapy by indocyanine green loaded polydopamine nanoparticles enhances anti-mammary gland tumor efficacy.

Various nano-targeted drug delivery systems have been developed for combined photothermal-photodynamic (PTT-PDT) treatment of tumors due to better outcomes compared with monomodality therapy. Here, we constructed a facile two-step method without core templates to obtain indocyanine green (ICG) loaded-hyaluronic acid (HA) surface-coated polydopamine nanoparticles (IIPH). The prepared nanoparticles demonstrated an excellent photothermal conversion capacity and efficient singlet oxygen production. Both in vitro and in vivo studies proved that IIPH could significantly inhibit the growth of tumor by PTT-PDT combinational treatment. All the results indicated that IIPH NPs hold great potential to be utilized as a new photothermal-photodynamic composite for cancer treatment.

Quasi-aligned Cu2S/Cu(OH)2nanorod arrays anchored on Cu foam as self-supported electrode for non-enzymatic glucose detection.

Self-supported Cu2S/Cu(OH)2composite nanorods for highly sensitive non-enzymatic glucose sensing werein situgrown on Cu foam by simple hydrothermal treatment of aligned Cu(OH)2nanorods. The physicochemical and electrochemical properties of the as-fabricated Cu2S/Cu(OH)2composite nanorods were characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, Raman spectroscope, x-ray photoelectron spectroscope, cyclic voltammetry, electrochemical impedance spectroscopy, amperometrici-tmeasurements. The mechanism of the composite nanorods produced on conductive substrates was also explored. The electrode exhibits a sensitivity of 9626.88µA mM-1cm-2towards glucose with good anti-interference ability, indicating it a promising electrode material for the enhanced non-enzymatic glucose detection.

A multifunctional nanoplatform for improving microwave hyperthermia by a combination therapy of vessel disruptive agent and immune modulator.

Microwave (MW) hyperthermia is one of the safest and most efficient minimally invasive tumor treatment methods, it is restricted by the bottlenecks of the heat sink effect and ineffective immune activation. Herein, a multifunctional nano platform with the load of nano immune modulator bimetallic metal-organic framework (BM), tumor vessel destructive agent and prodrug for gas production is developed for improving MW hyperthermia. Specifically, the combretastatin A4 phosphate (CA4P) was a vessel destructive agent to reduce MW heat loss by destructing the tumor blood vessel. Moreover, the as designed BM can scavenge the endogenic reactive oxygen species, which is conducive to hydrogen sulfide gas (H2S) that produced by bismuth sulfide (Bi2S3) to activate immune cells. Our in vivo experimental results demonstrate the destruction of tumor blood vessels coupled with the activated immune system results in the remarkable antitumor effect. This study provides an efficient strategy to improve MW hyperthermia by a combination of vasculature-targeting therapy with systemic immunity.

Gene delivery of chitosan-graft-polyethyleneimine vectors loaded on scaffolds for nerve regeneration.

As an important transcription factor, c-Jun could upregulate growth factors expression in Schwann cells (SCs). Arginine-Glycine-Aspartate (RGD)-functionalized chitosan-graft-polyethyleneimine (RCP) gene vectors were prepared through the maleic anhydride & the carbodiimide methods, and electrostatically bound with c-Jun plasmids (pJUN), finally loaded on poly-L-lactic acid/silk fibroin parallel fiber films to fabricate nerve scaffold (RCP/pJUN-PSPF@PGA), which could locally deliver c-Jun plasmids into SCs via the mediation of RGD peptides, and upregulate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in SCs. After the scaffold was bridged in sciatic nerve defect, the delivery of c-Jun plasmids from RCP/pJUN-PSPF@PGA facilitated SCs to sustain the expressions of NGF, BDNF and vascular endothelial growth factor in the injury field, promoting myelination, axonal growth and microvascular generation and nerve regeneration, muscle reinnervation and functional recovery. These results suggested that RCP/pDNA-PSPF@PGA, as an effective gene delivery platform, could provide a local gene therapy to improve nerve regeneration.

Coordination of Osteoblastogenesis and Osteoclastogenesis by the Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Matrix To Promote Bone Regeneration.

Extracellular matrix (ECM)-based therapies have been developed to improve bone repair because of their abundance of bioactive components. Besides the osteogenic promotion and the immune response, the potential effect of the ECM on the coordination between osteoblastogenesis and osteoclastogenesis in vivo should also deserve great attention because both osteoblasts and osteoclasts get involved in bone regeneration and are critical for the final repair outcome. Herein, based on our previous study on decellularization, antigen removal, and growth factor retention, porous poly (lactic-co-glycolic acid) (PLGA) scaffolds decorated with the bone marrow mesenchymal stem cell (BMSC)-derived ECM were prepared, and the functions of the ECM on BMSC osteogenic differentiation and osteoclastogenesis in vitro were preferentially investigated. Afterward, bone regeneration and osteoclast formation in vivo induced by ECM-decorated PLGA scaffolds were further studied. The in vitro tests revealed that ECM-decorated PLGA scaffolds obviously facilitated BMSC proliferation and osteogenic differentiation. However, when osteoclast precursors were cultured on the BMSC-derived ECM, the number and size of osteoclasts, expression of cathepsin K and matrix metalloproteinase 9, and tartrate-resistant acid phosphatase activity were notably decreased, accompanied by the reduction in the reactive oxygen species (ROS) level. Interestingly, the addition of exogenous hydrogen peroxide elevated the osteoclast amount on the ECM and up-regulated the resorption-related enzyme levels, implying that the repressive effect of the BMSC-derived ECM on osteoclasts may be related to the intracellular ROS. After implantation into calvarial defects, the ECM-decorated PLGA scaffolds significantly increased bone volume and bone mineral density compared with bare PLGA scaffolds and did not stimulate the overmuch formation of osteoclasts in vivo. This study evidenced that the BMSC-derived ECM may coordinate osteoblastogenesis and osteoclastogenesis and promote favorable bone formation without stimulating bone resorption.

Preliminary Study on the Antigen-Removal from Extracellular Matrix via Different Decellularization.

Due to the abundance of bioactive components, surficial decoration with cell-derived extracellular matrix (ECM) is a promising strategy to improve the biological functionality of the tissue engineering scaffolds. However, decellularization is necessary to remove antigenic components in the ECM that may trigger adverse immune response. Freeze-thaw (FT) cycles and treatment with Triton X-100/ammonium hydroxide (TN) are two commonly used decellularization methods for ECM, but their effects on both growth factor retention and antigen removal are still controversial. The objectives of this study are to compare the preservation of ECM texture and beneficial ingredients and the removal of cellular antigens by these two methods. First, the constructs combined bone marrow mesenchymal stem cell-derived ECM and poly(lactic-co-glycolic acid) (PLGA) membrane are prepared and decellularized using FT and TN treatments. Moreover, the effects of decellularization on the ultrastructure and the composition of ECM-decorated PLGA membrane are compared by scanning electron microscope observation and protein quantification. Furthermore, the ECM deposited on PLGA is stripped off and then implanted subcutaneously in rats, and the host macrophage and local lymphocyte responses were investigated. Finally, ECM-decorated porous PLGA scaffolds are implanted into rat calvarial defects, and the new bone formation is evaluated. Our results showed that both methods effectively removed DNA. TN treatment partially retained collagen, glycosaminoglycan, bone morphogenetic protein-2, and vascular endothelial growth factor, and better preserved structural integrity than FT treatment. ECM implants decellularized by both methods induced a mild host response after subcutaneous implantation. Although the total content of residual DNA in the two ECMs digested by the DNA enzyme seemed to be similar and very low, the interfaces between implanted materials and natural tissues in the TN group recruited lower numbers of CD68+ macrophages, CD68+CD86+ (M1) macrophages, and CD4+ T lymphocytes than that in FT group, implying that there exist other ECM antigens to influence immune response besides DNA. Furthermore, ECM-decorated scaffolds decellularized by TN treatment induced greater bone formation than that of bare scaffolds in vivo, demonstrating the effective retention of ECM bioactive components after decellularization. This study showed that TN treatment was a more effective and safer decellularization method than FT cycles. Impact statement Decellularization is a prerequisite for extracellular matrix (ECM) application, but there is still no standard for its selection. This study demonstrated that detergent treatment was more effective than freeze-thaw (FT) cycles in removing ECM antigens besides DNA, and the prepared ECM elicited a milder allogenic immune response, which ensured the safety of ECM. Moreover, detergent better preserved the ECM integrity than FT cycles, and effectively retained growth factors, and the decellularized ECM-decorated scaffolds significantly promoted bone repair, which ensured the effectiveness of ECM. This study provides the theoretical and experimental bases for the decellularization strategy of ECM-modified tissue engineering scaffolds.

MBG/ PGA-PCL composite scaffolds provide highly tunable degradation and osteogenic features.

It remains a challenge to achieve satisfactory balance between biodegradability and osteogenic capacity in biosynthetic bone grafts. In this study, we aimed to address this challenge by incorporating mesoporous bioactive glass (MBG) into poly(caprolactone-co-glycolide) (PGA-PCL) at gradient ratios. MBG/PGA-PCL (PGC/M) scaffolds with MBG incorporation ratio at 0, 10%, 25% and 40% (PGC/M0-40) were synthesized using a modified solvent casting-particulate leaching method, and their physiochemical and biological properties were comprehensively evaluated. PGC/M scaffolds exhibited highly perforated porous structure with a large-pore size of 300-450 µm, with ordered MBGs of around 6.0 nm mesopores size uniformly dispersed. The increase in MBG incorporation ratio significantly improved the scaffold surface hydrophilicity, apatite-formation ability and pH stability, increased the weight loss rate while insignificantly influenced the molecular chains degradation of PGA-PCL component, and facilitated the attachment, spreading, viability and proliferation of rat bone marrow stromal cells (rBMSCs) on scaffolds. Moreover, rBMSCs cultured on PGC/M10-40 scaffolds demonstrated enhanced ALP activity and osteogenesis-related gene expression in a MBG dose-dependent manner as compared with those cultured on PGC/M0 scaffolds. When implanted to the rat cranial bone defect, PGC/M25 and PGC/M40 scaffolds induced significantly better bone repair as compared to PGC/M0 and PGC/M10 scaffolds. Besides, the biodegradability of PGC/M scaffolds correlated with the MBG incorporation ratio. These data suggested this novel PGC/M scaffolds as promising bone repair biomaterial with highly tunable hydrophilicity, bioactivity, cytocompatibility, osteogenic activity as well as biodegradability.