Chirality of Copper-Amino Acid Nanoparticles Determines Chemodynamic Cancer Therapeutic Outcome.

Chirality is a prevalent characteristic in nature, where biological systems exhibit a significant preference for specific enantiomers of biomolecules. However, there is a limited exploration into utilizing nanomaterials' chirality to modulate their interactions with intracellular substances. In this study, self-assembled copper-cysteine chiral nanoparticles and explore the influence of their charity on cancer chemodynamic therapy (CDT) are fabricated. Experimental and molecular dynamics (MD) simulation results demonstrate that the copper-l-cysteine chiral nanoparticles (Cu-l-Cys NPs) exhibit a stronger affinity toward l-glutathione (l-GSH) that is overproduced in cancer cells, compared to the copper-d-cysteine enantiomer (Cu-d-Cys NPs). The interaction between Cu-l-Cys NPs and l-GSH triggers a redox reaction that depletes l-GSH and converts Cu2+ into Cu+. Subsequently, Cu+ catalyzes a Fenton-like reaction, decomposing H2O2 into highly cytotoxic hydroxyl radicals (•OH) for cancer CDT. In vivo, results confirm that Cu-l-Cys NPs with good biocompatibility elicit a pronounced cancer cell death and effectively inhibit tumor growth. This work proposes a new perspective on chirality-enhanced cancer therapy.

Hydro-Sensitive, In Situ Ultrafast Physical Self-Gelatinizing, and Red Blood Cells Strengthened Hemostatic Adhesive Powder with Antibiosis and Immunoregulation for Wound Repair.

Immediate and effective hemostatic treatments for complex bleeding wounds are an urgent clinical demand. Hemostatic materials with characteristics of adhesion, sealing, anti-infection, and concrescence promotion have drawn growing concerns. However, pure natural multifunctional hemostatic materials with in situ ultrafast self-gelation are rarely reported. In this study, a hydro-sensitive collagen/tannic acid (ColTA) natural hemostatic powder is developed that can in situ self-gel to form adhesive by the non-covalent crosslinking between tannic acid (TA) and collagen (Col) in liquids. The physical interactions endow ColTA adhesive with the characteristics of instantaneous formation and high adhesion at various substrate surfaces. Crucially, ColTA powder adhesive shows an enhanced adhesion performance in the presence of blood due to the electrostatic interactions between ColTA adhesive and red blood cells, conducive to effective in situ sealing and rapid hemostasis. The biocompatible and hemocompatible ColTA adhesive can effectively control bleeding and seal the wounds of the caudal vein, liver, heart, and femoral arteries in rats. Furthermore, the low-cost and ready-to-use ColTA adhesive powder also possesses good antibacterial and inhibiting biofilm formation ability, and can efficiently regulate immune response by the NF-κB pathway to promote wound repair, making it a highly promising hemostatic material with great potential for biomedical applications.

Cartilage-Inspired Inhomogeneous Salt-Hydrogel for Hydrated Drag-Reducing and Strain Sensing.

Articular cartilages exhibit load-bearing capacity and durability due to their inhomogeneous structure. Inspired by this unique structure, a tough and inhomogeneous salt-hydrogel was developed by trapping sodium acetate (NaAc) crystals in polyacrylamide (PAM) polymer networks and then partially redissolving the NaAc crystals. The compressive and tensile stresses of the salt-hydrogel increase significantly by more than 20 times when oversaturated Ac- and Na+ are introduced into the gel network. Such an enhancement in mechanical strength is primarily attributed to the formation of NaAc crystals within the gel network. Further investigations reveal that the mechanical strength of the salt-hydrogel is temperature-dependent as the NaAc crystals gradually redissolve in the gel network with increasing temperature. Furthermore, redissolving NaAc crystals in an aqueous solution can yield an inhomogeneous salt-hydrogel. The topmost soft surface of the salt-hydrogel offers hydration lubrication, while the inhomogeneous network confers load-bearing capacity and durability. Compared to regular hydrogels, the inhomogeneous salt-hydrogel surface can realize drag reduction and remain smooth without damage after the friction tests. Moreover, a salt-hydrogel coating is also fabricated to visually demonstrate its drag-reducing property. In addition, this salt-hydrogel possesses conductivity and can be utilized in the development of inhomogeneous salt-hydrogel fibers (diameter = 438 ± 7 µm) for strain detection. The produced salt-hydrogel fiber exhibits excellent durability and reproducibility as a strain sensor, capable of detecting both small strains (e.g., 1%) and large strains (e.g., 40%). This work provides fundamental insights into developing hydrogels with an inhomogeneous network and explores their potential applications (e.g., hydrated drag-reducing, strain sensing).

Janus porous polylactic acid membranes with versatile metal-phenolic interface for biomimetic periodontal bone regeneration.

Conventional treatment to periodontal and many other bone defects requires the use of barrier membranes to guided tissue regeneration (GTR) and guided bone regeneration (GBR). However, current barrier membranes normally lack of the ability to actively regulate the bone repairing process. Herein, we proposed a biomimetic bone tissue engineering strategy enabled by a new type of Janus porous polylactic acid membrane (PLAM), which was fabricated by combining unidirectional evaporation-induced pore formation with subsequent self-assembly of a bioactive metal-phenolic network (MPN) nanointerface. The prepared PLAM-MPN simultaneously possesses barrier function on the dense side and bone-forming function on the porous side. In vitro, the presence of MPN nanointerface potently alleviated the proinflammatory polarization of mice bone marrow-derived macrophages (BMDMs), induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and enhanced the attachment, migration and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The implantation of PLAM-MPN into rat periodontal bone defects remarkably enhanced bone regeneration. This bioactive MPN nanointerface within a Janus porous membrane possesses versatile capacities to regulate cell physiology favoring bone regeneration, demonstrating great potential as GTR and GBR membranes for clinical applications.

Surface-Confined Piezocatalysis Inspired by ROS Generation of Mitochondria Respiratory Chain for Ultrasound-Driven Noninvasive Elimination of Implant Infection.

Implant-associated infections (IAI) are great challenges to medical healthcare and human wellness, yet current clinical treatments are limited to the use of antibiotics and physical removal of infected tissue or the implant. Inspired by the protein/membrane complex structure and its generation of reactive oxygen species in the mitochondria respiration process of immune cells during bacteria invasion, we herein propose a metal/piezoelectric nanostructure embedded on the polymer implant surface to achieve efficient piezocatalysis for combating IAI. The piezoelectricity-enabled local electron discharge and the induced oxidative stress generated at the implant-bacteria interface can efficiently inhibit the activity of the attachedStaphylococcus aureusby cell membrane disruption and sugar energy exhaustion, possess high biocompatibility, and eliminate the subcutaneous infection by simply applying the ultrasound stimulation. For further demonstration, the treatment of root canal reinfection with simplified procedures has been achieved by using piezoelectric gutta-percha implanted in ex vivo human teeth. This surface-confined piezocatalysis antibacterial strategy, which takes advantage of the limited infection interspace, easiness of polymer processing, and noninvasiveness of sonodynamic therapy, has potential applications in IAI treatment.

A multifunctional chitosan-based hydrogel with self-healing, antibacterial, and immunomodulatory effects as wound dressing.

Bacterial infection often leads to inflammatory responses and delays wound healing. Chitosan (CS)-based composite hydrogels can hold desirable mechanical properties and maintain excellent antibacterial abilities, and thus may be promising as wound dressings. Although CS-based hydrogels have been widely studied on the antibacterial and wound-healing abilities, their immunomodulatory abilities were rarely evaluated. Herein, we developed a multifunctional CS/Poly[2-(methacryloyloxy)ethyl] trimethyl ammonium chloride (PMETAC) hydrogel. In vitro, this hydrogel exhibited self-healing ability and excellent biocompatibility, promoted macrophage polarization towards M2 phenotype, and showed desirable antibacterial activity. In vivo, this hydrogel accelerated the wound regeneration process by reducing bacterial burden, increasing collagen deposition, stimulating angiogenesis, promoting macrophage polarization to M2 direction, and shifting the balance of T helper type 17 (Th17) cells towards anti-inflammatory regulatory T (Treg) cells. This work revealed the potential immunomodulatory effect of CS-based wound dressings and thus may provide a novel target for developing efficient wound healing tools.

Growth of ZIF-8 Nanoparticles In Situ on Graphene Oxide Nanosheets: A Multifunctional Nanoplatform for Combined Ion-Interference and Photothermal Therapy.

The regulation of intracellular ions' overload to interrupt normal bioprocesses and cause cell death has been developed as an efficient strategy (named as ion-interference therapy/IIT) to treat cancer. In this study, we design a multifunctional nanoplatform (called BSArGO@ZIF-8 NSs) by in situ growth of metal organic framework nanoparticles (ZIF-8 NPs) onto the graphene oxide (GO) surface, subsequently reduced by ascorbic acid and modified by bovine serum albumin. This nanocomplex causes the intracellular overload of Zn2+, an increase of reactive oxygen species (ROS), and exerts a broad-spectrum lethality to different kinds of cancer cells. BSArGO@ZIF-8 NSs can promote cell apoptosis by initiating bim (a pro-apoptotic protein)-mediated mitochondrial apoptotic events, up-regulating PUMA/NOXA expression, and down-regulating the level of Bid/p53AIP1. Meanwhile, Zn2+ excess triggers cellular dysfunction and mitochondria damage by activating the autophagy signaling pathways and disturbing the intracellular environmental homeostasis. Combined with the photothermal effect of reduced GO (rGO), BSArGO@ZIF-8 NSs mediated ion-interference and photothermal combined therapy leads to effective apoptosis and inhibits cell proliferation and angiogenesis, bringing a higher efficacy in tumor suppression in vivo. This designed Zn-based multifunctional nanoplatform will allow promoting further the development of IIT and the corresponding combined cancer therapy strategy.

Hazard assessment of abraded thermoplastic composites reinforced with reduced graphene oxide.

Graphene-related materials (GRMs) are subject to intensive investigations and considerable progress has been made in recent years in terms of safety assessment. However, limited information is available concerning the hazard potential of GRM-containing products such as graphene-reinforced composites. In the present study, we conducted a comprehensive investigation of the potential biological effects of particles released through an abrasion process from reduced graphene oxide (rGO)-reinforced composites of polyamide 6 (PA6), a widely used engineered thermoplastic polymer, in comparison to as-produced rGO. First, a panel of well-established in vitro models, representative of the immune system and possible target organs such as the lungs, the gut, and the skin, was applied. Limited responses to PA6-rGO exposure were found in the different in vitro models. Only as-produced rGO induced substantial adverse effects, in particular in macrophages. Since inhalation of airborne materials is a key occupational concern, we then sought to test whether the in vitro responses noted for these materials would translate into adverse effects in vivo. To this end, the response at 1, 7 and 28 days after a single pulmonary exposure was evaluated in mice. In agreement with the in vitro data, PA6-rGO induced a modest and transient pulmonary inflammation, resolved by day 28. In contrast, rGO induced a longer-lasting, albeit moderate inflammation that did not lead to tissue remodeling within 28 days. Taken together, the present study suggests a negligible impact on human health under acute exposure conditions of GRM fillers such as rGO when released from composites at doses expected at the workplace.

Gold Nanostrip Array-Mediated Wireless Electrical Stimulation for Accelerating Functional Neuronal Differentiation.

Neural stem cell (NSC)-based therapy holds great promise for the treatment of neurodegenerative diseases. Presently, however, it is hindered by poor functional neuronal differentiation. Electrical stimulation is considered one of the most effective ways to promote neuronal differentiation of NSCs. In addition to surgically implanted electrodes, traditional electrical stimulation includes wires connected to the external power supply, and an additional surgery is required to remove the electrodes or wires following stimulation, which may cause secondary injuries and infections. Herein, a novel method is reported for generation of wireless electrical signals on an Au nanostrip array by leveraging the effect of electromagnetic induction under a rotating magnetic field. The intensity of the generated electrical signals depends on the rotation speed and magnetic field strength. The Au nanostrip array-mediated electric stimulation promotes NSC differentiation into mature neurons within 5 days, at the mRNA, protein, and function levels. The rate of differentiation is faster by at least 5 days than that in cells without treatment. The Au nanostrip array-based wireless device also accelerates neuronal differentiation of NSCs in vivo. The novel method to accelerate the neuronal differentiation of NSCs has the advantages of wireless, timely, localized and precise controllability, and noninvasive power supplementation.

Sustained and Microenvironment-Accelerated Release of Minocycline from Alginate Injectable Hydrogel for Bacteria-Infected Wound Healing.

During wound healing, bacterial infection is one of the main limiting factors for the desired efficiency. Wound dressing-mediated antibiotics therapies could overcome this problem to a great extent due to sustained drug release and controllable dose. Here, we designed a kind of alginate injectable hydrogel loaded with minocycline (SA@MC) as a dressing for staphylococcus aureus-infected wound healing. SA@MC hydrogel possessed good injectability and can be injected by syringes. MC participated in the gel formation, causing the microstructure change based on the morphology characterization. The element mapping and FT-IR spectra further confirmed the successful loading of MC in SA hydrogel. Interestingly, MC was released more efficiently in a weakly alkaline condition (pH 7-8) than in a weakly acidic condition (pH 4-6) from SA@MC injectable hydrogel, which means that there is an accelerated release to respond to the weakly alkaline wound microenvironment. Meanwhile, SA@MC injectable hydrogel had high biocompatibility and excellent antibacterial activity due to the sustained release of MC. Further, in vivo experiment results demonstrated that SA@MC injectable hydrogel promoted staphylococcus aureus-infected wound healing efficiently. In summary, the injectable composite hydrogel can serve as an ideal dressing to prevent bacterial infection and promote wound healing.

2D Materials and Primary Human Dendritic Cells: A Comparative Cytotoxicity Study.

Human health can be affected by materials indirectly through exposure to the environment or directly through close contact and uptake. With the ever-growing use of 2D materials in many applications such as electronics, medical therapeutics, molecular sensing, and energy storage, it has become more pertinent to investigate their impact on the immune system. Dendritic cells (DCs) are highly important, considering their role as the main link between the innate and the adaptive immune system. By using primary human DCs, it is shown that hexagonal boron nitride (hBN), graphene oxide (GO) and molybdenum disulphide have minimal effects on viability. In particular, it is evidenced that hBN and GO increase DC maturation, while GO leads to the release of reactive oxygen species and pro-inflammatory cytokines. hBN and MoS2 increase T cell proliferation with and without the presence of DCs. hBN in particular does not show any sign of downstream T cell polarization. The study allows ranking of the three materials in terms of inherent toxicity, providing the following trend: GO > hBN ≈ MoS2 , with GO the most cytotoxic.

Metal Phenolic Nanodressing of Porous Polymer Scaffolds for Enhanced Bone Regeneration via Interfacial Gating Growth Factor Release and Stem Cell Differentiation.

Porous polymer scaffolds are essential materials for tissue engineering because they can be easily processed to deliver stem cells or bioactive factors. However, scaffolds made of synthetic polymers normally lack a bioactive cell-material interface and undergo a burst release of growth factors, which may hinder their further application in tissue engineering. In this paper, a metal-phenolic network (MPN) was interfacially constructed on the pore surface of a porous poly(dl-lactide) (PPLA) scaffold. Based on the molecular gating property of the MPN supramolecular structure, the PPLA@MPN scaffold achieved the sustained release of the loaded molecules. In addition, the MPN coating provided a bioactive interface, thus encouraging the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The PPLA@MPN scaffolds exhibited enhanced bone regeneration in a rat femoral defect model in vivo compared to PPLA, which is ascribed to the combined effect of sustained bone morphogenetic protein-2 (BMP-2) release and the osteogenic ability of MPN. This nanodressing technique provides a viable and straightforward strategy for enhancing the performance of porous polymer scaffolds in bone tissue engineering.

Recent Advances in 2D Material-Mediated Immuno-Combined Cancer Therapy.

In the last years, cancer immunotherapy has started to attract a lot of attention, becoming one of the alternatives in the clinical treatment of cancer. Indeed, one of the advantages of immunotherapy is that both primary and distant tumors can be efficiently eradicated through a triggered immune response. Due to their large specific surface area and unique physicochemical properties, 2D materials have become popular in cancer immunotherapy, especially as efficient drug carriers. They have been also exploited as photothermal platforms, chemodynamic agents, and photosensitizers to further enhance the efficacy of the therapy. In this review, the focus is on the recent development of 2D materials as new tools to combine immunotherapy with chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, radiotherapy, and radiodynamic therapy. These innovative synergistic approaches intend to go beyond the classical strategies based on a simple delivery function of immune modulators by nanomaterials. Furthermore, the effects of the 2D materials themselves and their surface properties (e.g., chemical modification and protein corona formation) on the induction of an immune response will be also discussed.

Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods.

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.

Gingipain-Responsive Thermosensitive Hydrogel Loaded with SDF-1 Facilitates In Situ Periodontal Tissue Regeneration.

Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide-short antimicrobial peptide (SAMP)-anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results in vitro indicated the PEGPD@SDF-1 hydrogel exhibited preferable biocompatibility and could promote the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Antibacterial testing demonstrated that the PEGPD@SDF-1 hydrogel released the SAMP stressfully in response to gingipain stimulation, thereby strongly inhibiting the growth of Porphyromonas gingivalis. Furthermore, the study in vivo indicated that the PEGPD@SDF-1 hydrogel inhibited P. gingivalis reproduction, created a low-inflammatory environment, facilitated the recruitment of CD90+/CD34- stromal cells, and induced osteogenesis. Taken together, these results suggest that the gingipain-responsive PEGPD@SDF-1 hydrogel could facilitate in situ periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.

Unilateral Silver-Loaded Silk Fibroin Difunctional Membranes as Antibacterial Wound Dressings.

Silk fibroin (SF) has been widely used as wound dressings due to its good biocompatibility. To enhance the antibacterial properties of the dressings, silver (Ag) is often added. However, an overdose of Ag may cause cytotoxicity and inhibit wound healing. Therefore, this study aimed to develop a two-layered membrane to reduce cytotoxicity while maintaining the antibacterial properties of Ag through a simplified layer-by-layer technique. The membranes comprised an Ag-rich SF layer (Ag-SF) and a pure SF layer. The unilateral Ag-loaded membranes showed efficient antibacterial properties at doses above 0.06 mg/mL Ag, and the antibacterial properties were comparable on both sides. In contrast, the SF sides of the membranes showed lower cytotoxicity than the Ag-SF sides of the membranes. Further studies on the thickness ratio of Ag-SF/SF layers revealed that Ag0.12-SF/SF membranes with a ratio of 1:3 had high cytocompatibility on the SF sides while holding a strong antibacterial property. Besides, the SF sides of the Ag0.12-SF/SF1:3 membranes promoted the expression levels of collagen I and transforming growth factor-ß mRNA in human foreskin fibroblasts. The SF sides of the Ag0.12-SF/SF1:3 membranes significantly promoted the healing of infected wounds in vivo. Therefore, unilateral loading with the simplified layer-by-layer preparation technique provided an effective method to balance the cytotoxicity and the antibacterial property of Ag-loaded materials and thus form a broader therapeutic window for Ag applications. The unilateral Ag-loaded silk fibroin difunctional membranes have the potential to be further preclinically explored as wound dressings.

Wireless Localized Electrical Stimulation Generated by an Ultrasound-Driven Piezoelectric Discharge Regulates Proinflammatory Macrophage Polarization.

Proinflammatory (M1) macrophages play a vital role in antitumor immunity, and regulation of proinflammatory macrophage polarization is critical for immunotherapy. The polarization of macrophages can be regulated by biological or chemical stimulation, but investigations of the regulatory effect of physical stimulation are limited. Herein, regulating macrophage polarization with localized electrical signals derived from a piezoelectric ß-phase poly(vinylidene fluoride) (ß-PVDF) film in a wireless mode is proposed. Charges released on the surface of the ß-PVDF film driven by ultrasonic irradiation can significantly enhance the M1 polarization of macrophages. Mechanistic investigation confirms that electrical potentials rather than reactive oxygen species and mechanical forces enable Ca2+ influx through voltage-gated channels and establishment of the Ca2+-CAMK2A-NF-κB axis to promote the proinflammatory macrophage response during ultrasound treatment. Piezoelectric material-mediated electrical signal-activated proinflammatory macrophages significantly inhibit tumor cell proliferation. A method for electrogenetic regulation of immune cells as well as a powerful tool for engineering macrophages for immunotherapy is provided here.

[Advances in the Application of Hydroxyapatite Composite Materials in Bone Tissue Engineering].

Hydroxyapatite (HAp) is the main inorganic component of the bones and teeth, and it possesses bioactivity and biocompatibility. However, due to its poor mechanical performance, slow degradation speed, and lack of diversity in its function, it is difficult to apply HAp alone as a scaffold material for bone tissue engineering. By combining HAp with other types of materials, composite materials with specific properties can be prepared, and the scopes of HAp applications can be expanded. Firstly, we elaborated on the importance, and strengths and weaknesses of HAp for bone tissue engineering biomaterials and then reviewed the research status of HAp composite materials used in bone regeneration. Secondly, about hot research topics in the field of applying HAp composite materials in bone repair, we summarized the representative findings in the field, and discussions and analysis were made accordingly. Finally, we also examined the future development prospects of HAp composite bone repair materials.

Reaction between Graphene Oxide and Intracellular Glutathione Affects Cell Viability and Proliferation.

Graphene oxide (GO) is currently developed for biomedical applications as a promising nanoplatform for drug delivery, phototherapy, and biosensing. As a consequence, its safety and cytotoxicity issues have attracted extensive attention. It has been demonstrated that GO causes an increase of intracellular oxidative stress, likely leading to its cytotoxicity and inhibition of cell proliferation. Being one of the main reductive intracellular substances, glutathione (GSH) is vital in the regulation of the oxidative stress level to maintain normal cellular functions. In this study, we found that GSH could be oxidized to GSSG by GO, leading to the formation of reduced GO (rGO). GSH depletion affects the intracellular reductive/oxidative balance, provoking the increase of the reactive oxygen species level, sequentially inhibiting cell viability and proliferation. Therefore, the reaction between GO and GSH provides a new perspective to explain the origin of GO cytotoxicity.

Dimethyloxallyl glycine/nanosilicates-loaded osteogenic/angiogenic difunctional fibrous structure for functional periodontal tissue regeneration.

The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration. Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering, most of them are macromolecular proteins with the drawbacks of short effective half-life, poor stability and high cost, which constrain their clinical translation. Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule, dimethyloxalylglycine (DMOG), and an osteoinductive inorganic nanomaterial, nanosilicate (nSi) into poly (lactic-co-glycolic acid) (PLGA) fibers by electrospinning. The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized. Thereafter, the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro. Additionally, the fibrous membranes were transplanted into rat periodontal defects, and tissue regeneration was assessed with histological evaluation, micro-computed tomography (micro-CT), and immunohistochemical analysis. DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility. PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers, higher alkaline phosphatase (ALP) activity, and more tube formation in comparison with single application. Further, in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34- stromal cells, induced angiogenesis and osteogenesis, and regenerated cementum-ligament-bone complex in periodontal defects. Consequently, the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration. DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis, and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.