Superconductivity above 105 K in Nonclathrate Ternary Lanthanum Borohydride below Megabar Pressure.

Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as ∼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.

Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma.

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

High-Performance Broadband Image Sensing Photodetector Based on MnTe/WS2 van der Waals Epitaxial Heterostructures.

Two-dimensional transition metal dichalcogenide (TMDC) heterostructure is receiving considerable attention due to its novel electronic, optoelectronic, and spintronic devices with design-oriented and functional features. However, direct design and synthesis of high-quality TMDC/MnTe heterostructures remain difficult, which severely impede further investigations of semiconductor/magnetic semiconductor devices. Herein, the synthesis of high-quality vertically stacked WS2/MnTe heterostructures is realized via a two-step chemical vapor deposition method. Raman, photoluminescence, and scanning transmission electron microscopy characterizations reveal the high-quality and atomically sharp interfaces of the WS2/MnTe heterostructure. WS2/MnTe-based van der Waals field effect transistors demonstrate high rectification behavior with rectification ratio up to 106, as well as a typical p-n electrical transport characteristic. Notably, the fabricated WS2/MnTe photodetector exhibits sensitive and broadband photoresponse ranging from UV to NIR with a maximum responsivity of 1.2 × 103 A/W, a high external quantum efficiency of 2.7 × 105%, and fast photoresponse time of ∼50 ms. Moreover, WS2/MnTe heterostructure photodetectors possess a broadband image sensing capability at room temperature, suggesting potential applications in next-generation high-performance and broadband image sensing photodetectors.

Plasmonic Imaging of Single DNA with Charge Sensitive Monolayer WS2.

Imaging the surface charge of biomolecules such as proteins and DNA, is crucial for comprehending their structure and function. Unfortunately, current methods for label-free, sensitive, and rapid imaging of the surface charge of single DNA molecules are limited. Here, we propose a plasmonic microscopy strategy that utilizes charge-sensitive single-crystal monolayer WS2 materials to image the local charge density of a single λ-DNA molecule. Our study reveals that WS2 is a highly sensitive charge-sensitive material that can accurately measure the local charge density of λ-DNA with high spatial resolution and sensitivity. The consistency of the surface charge density values obtained from the single-crystal monolayer WS2 materials with theoretical simulations demonstrates the reliability of our approach. Our findings suggest that this class of materials has significant implications for the development of label-free, scanning-free, and rapid optical detection and charge imaging of biomolecules.

Ultrasensitive CCL2 Detection in Urine for Diabetic Nephropathy Diagnosis Using a WS2-Based Plasmonic Biosensor.

The accurate diagnosis of diabetic nephropathy relies on achieving ultrasensitive biosensing for biomarker detection. However, existing biosensors face challenges such as poor sensitivity, complexity, time-consuming procedures, and high assay costs. To address these limitations, we report a WS2-based plasmonic biosensor for the ultrasensitive detection of biomarker candidates in clinical human urine samples associated with diabetic nephropathy. Leveraging plasmonic-based electrochemical impedance microscopy (P-EIM) imaging, we observed a remarkable charge sensitivity in monolayer WS2 single crystals. Our biosensor exhibits an exceptionally low detection limit (0.201 ag/mL) and remarkable selectivity in detecting CC chemokine ligand 2 (CCL2) protein biomarkers, outperforming conventional techniques such as ELISA. This work represents a breakthrough in traditional protein sensors, providing a direction and materials foundation for developing ultrasensitive sensors tailored to clinical applications for biomarker sensing.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Novel hydrocolloids synthesized by polyphenols grafted onto chitosan: A promising coating to inhibit PhIP formation during pan-frying of golden pompano fillets.

Hydrocolloids synthesized by gallic acid (GA) and ferulic acid (FA) grafting onto chitosan (CS) were characterized, and their effects on PhIP formation in pan-fried golden pompano were investigated. Spectrograms including nuclear magnetic resonance, Fourier transform infrared spectroscopy and ultraviolet-visible confirmed that GA and FA were successfully grafted onto CS via covalent bonds, with grafting degree of 97.06 ± 2.56 mg GA/g and 93.56 ± 2.76 mg FA/g, respectively. The CS-g-GA and CS-g-FA exerted better solubility and antioxidant activities than CS. For the 8-min pan-fried golden pompano fillets, CS-g-GA and CS-g-FA (0.5 %, m/v) significantly reduced the PhIP formation by 61.71 % and 81.64 %, respectively. Chemical models revealed that CS-g-GA and CS-g-FA inhibited PhIP formation mainly by decreasing the phenylacetaldehyde contents from Maillard reaction and competing with creatinine to react with phenylacetaldehyde. Therefore, it was suggested that CS-g-phenolic acids emerge as novel coating for aquatic products during processing and inhibit heterocyclic amines generation.

Plasma-activated water in combination with coconut exocarp flavonoids emerge as promising preservation technique for golden pompano: Impact of the treatment sequence.

In the current study, the preservation effect of plasma-activated water (PAW), coconut exocarp flavonoids (CF) and their combination on golden pompano fillets during refrigerated storage was investigated with emphasize on the treating sequence. PAW effectively inactivated spoilage bacteria and inhibited total volatile basic nitrogen (TVB-N) increase, while boosted the TBARS and carbonyl values. PAW+CF exerted synergistic effect on extending the period before total bacterial count and TVB-N content reaching acceptance limit than PAW or CF alone (P < 0.05). In addition, their combined treatment effectively reduced fillets discoloration and texture deterioration. Simultaneously, lipid and protein oxidation were significantly inhibited, which was comparable to CF. It was indicated that the treatment sequence of PAW and CF profoundly impact the preservation effect. Specifically, prior CF marinating followed by PAW was more effective than the opposite sequence. Thus, combination of CF followed by PAW served as promising technique for fish fillets preservation.

Ferroelectric Bi2O2Te-Based Plasmonic Biosensor for Ultrasensitive Biomolecular Detection.

Ultrasensitive detection of biomarkers, particularly proteins, and microRNA, is critical for disease early diagnosis. Although surface plasmon resonance biosensors offer label-free, real-time detection, it is challenging to detect biomolecules at low concentrations that only induce a minor mass or refractive index change on the analyte molecules. Here an ultrasensitive plasmonic biosensor strategy is reported by utilizing the ferroelectric properties of Bi2O2Te as a sensitive-layer material. The polarization alteration of ferroelectric Bi2O2Te produces a significant plasmonic biosensing response, enabling the detection of charged biomolecules even at ultralow concentrations. An extraordinary ultralow detection limit of 1 fm is achieved for protein molecules and an unprecedented 0.1 fm for miRNA molecules, demonstrating exceptional specificity. The finding opens a promising avenue for the integration of 2D ferroelectric materials into plasmonic biosensors, with potential applications spanning a wide range.

Effect of a collagen peptide-fish oil high internal phase emulsion on the printability and gelation of 3D-printed surimi gel inks.

The effect of a high internal phase emulsion (HIPE) on three-dimensional-printed surimi gel inks was studied. Increasing the concentration of collagen peptide decreased the particle size of HIPE droplets and improved the viscoelasticity and stability. For example, when the collagen peptide concentration was 5 wt%, the viscoelasticity of the HIPE was high, as indicated by the presence of small and uniform particles, which formed a monolayer in the outer layer of the oil droplets to form stable a HIPE. A HIPE was used as the filling material to fill the surimi gel network, which reduced the porosity of the network. Surimi protein and peptides have dual emulsifying effects on the stabilization of oil. After adding the emulsion, the texture, gel properties and rheological properties of the surimi were reduced, and its printing adaptability was improved. This study provides new ideas for the production of surimi and its application in 3D printing.

Alterations in metabolome and microbiome: new clues on cathelicidin-related antimicrobial peptide alleviates acute ulcerative colitis.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidin-related antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota.

Twisted-layer boron nitride ceramic with high deformability and strength.

Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1-5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.

Isotope engineering for spin defects in van der Waals materials.

Spin defects in van der Waals materials offer a promising platform for advancing quantum technologies. Here, we propose and demonstrate a powerful technique based on isotope engineering of host materials to significantly enhance the coherence properties of embedded spin defects. Focusing on the recently-discovered negatively charged boron vacancy center ([Formula: see text]) in hexagonal boron nitride (hBN), we grow isotopically purified h10B15N crystals. Compared to [Formula: see text] in hBN with the natural distribution of isotopes, we observe substantially narrower and less crowded [Formula: see text] spin transitions as well as extended coherence time T2 and relaxation time T1. For quantum sensing, [Formula: see text] centers in our h10B15N samples exhibit a factor of 4 (2) enhancement in DC (AC) magnetic field sensitivity. For additional quantum resources, the individual addressability of the [Formula: see text] hyperfine levels enables the dynamical polarization and coherent control of the three nearest-neighbor 15N nuclear spins. Our results demonstrate the power of isotope engineering for enhancing the properties of quantum spin defects in hBN, and can be readily extended to improving spin qubits in a broad family of van der Waals materials.

Structural transition and migration of incoherent twin boundary in diamond.

Grain boundaries (GBs), with their diversity in both structure and structural transitions, play an essential role in tailoring the properties of polycrystalline materials1-5. As a unique GB subset, {112} incoherent twin boundaries (ITBs) are ubiquitous in nanotwinned, face-centred cubic materials6-9. Although multiple ITB configurations and transitions have been reported7,10, their transition mechanisms and impacts on mechanical properties remain largely unexplored, especially in regard to covalent materials. Here we report atomic observations of six ITB configurations and structural transitions in diamond at room temperature, showing a dislocation-mediated mechanism different from metallic systems11,12. The dominant ITBs are asymmetric and less mobile, contributing strongly to continuous hardening in nanotwinned diamond13. The potential driving forces of ITB activities are discussed. Our findings shed new light on GB behaviour in diamond and covalent materials, pointing to a new strategy for development of high-performance, nanotwinned materials.

BpGRP1 acts downstream of BpmiR396c/BpGRF3 to confer salt tolerance in Betula platyphylla.

Glycine-rich RNA-binding proteins (GRPs) have been implicated in the responses of plants to environmental stresses, but the function of GRP genes involved in salt stress and the underlying mechanism remain unclear. In this study, we identified BpGRP1 (glycine-rich RNA-binding protein), a Betula platyphylla gene that is induced under salt stress. The physiological and molecular responses to salt tolerance were investigated in both BpGRP1-overexpressing and suppressed conditions. BpGRF3 (growth-regulating factor 3) was identified as a regulatory factor upstream of BpGRP1. We demonstrated that overexpression of BpGRF3 significantly increased the salt tolerance of birch, whereas the grf3-1 mutant exhibited the opposite effect. Further analysis revealed that BpGRF3 and its interaction partner, BpSHMT, function upstream of BpGRP1. We demonstrated that BpmiR396c, as an upstream regulator of BpGRF3, could negatively regulate salt tolerance in birch. Furthermore, we uncovered evidence showing that the BpmiR396c/BpGRF3 regulatory module functions in mediating the salt response by regulating the associated physiological pathways. Our results indicate that BpmiR396c regulates the expression of BpGRF3, which plays a role in salt tolerance by targeting BpGRP1.

MICDnet: Multimodal information processing networks for Crohn's disease diagnosis.

Crohn's disease (CD) is a chronic inflammatory disease with increasing incidence worldwide and unclear etiology. Its clinical manifestations vary depending on location, extent, and severity of the lesions. In order to diagnose Crohn's disease, medical professionals need to comprehensively analyze patients' multimodal examination data, which includes medical imaging such as colonoscopy, pathological, and text information from clinical records. The processes of multimodal data analysis require collaboration among medical professionals from different departments, which wastes a lot of time and human resources. Therefore, a multimodal medical assisted diagnosis system for Crohn's disease is particularly significant. Existing network frameworks find it hard to effectively capture multimodal patient data for diagnosis, and multimodal data for Crohn's disease is currently lacking. In addition,a combination of data from patients with similar symptoms could serve as an effective reference for disease diagnosis. Thus, we propose a multimodal information diagnosis network (MICDnet) to learn CD feature representations by integrating colonoscopy, pathology images and clinical texts. Specifically, MICDnet first preprocesses each modality data, then uses encoders to extract image and text features separately. After that, multimodal feature fusion is performed. Finally, CD classification and diagnosis are conducted based on the fused features. Under the authorization, we build a dataset of 136 hospitalized inspectors, with colonoscopy images of seven areas, pathology images, and clinical record text for each individual. Training MICDnet on this dataset shows that multimodal diagnosis can improve the diagnostic accuracy of CD, and the diagnostic performance of MICDnet is superior to other models.

Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3.

OBJECTIVE: Nowadays, more than 90% of people over 50 years suffer from intervertebral disc degeneration (IDD), but there are exist no ideal drugs. The aim of this study is to identify a new drug for IDD. METHODS: An approved small molecular drug library including 2040 small molecular compounds was used here. We found that taurocholic acid sodium hydrate (NAT) could induce chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs). Then, an in vivo mouse model of IDD was established and the coccygeal discs transcriptome analysis and surface plasmon resonance analysis (SPR) integrated with liquid chromatography-tandem mass spectrometry assay (LC-MS) were performed in this study to study the therapy effect and target proteins of NAT for IDD. Micro-CT was used to evaluate the cancellous bone. The expression of osteogenic (OCN, RNX2), chondrogenic (COL2A1, SOX9), and the target related (ERK1/2, p-ERK1/2) proteins were detected. The alkaline phosphatase staining was performed to estimate osteogenic differentiation. Blood routine and blood biochemistry indexes were analyzed for the safety of NAT. RESULTS: The results showed that NAT could induce chondrogenesis and osteogenesis in MSCs. Further experiments confirmed NAT could ameliorate the secondary osteoporosis and delay the development of IDD in mice. Transcriptome analysis identified 128 common genes and eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for NAT. SPR-LC-MS assay detected 57 target proteins for NAT, including MAPK3 (mitogen-activated protein kinase 3), also known as ERK1 (extracellular regulated protein kinase 1). Further verification experiment confirmed that NAT significantly reduced the expression of ERK1/2 phosphorylation. CONCLUSION: NAT would induce chondrogenesis and osteogenesis of MSCs, ameliorate the secondary osteoporosis and delay the progression of IDD in mice by targeting MAPK3.Furthermore, MAPK3, especially the phosphorylation of MAPK3, would be a potential therapeutic target for IDD treatment.

Bp-miR408a participates in osmotic and salt stress responses by regulating BpBCP1 in Betula platyphylla.

The microRNAs, which are small RNAs of 18-25 nt in length, act as key regulatory factors in posttranscriptional gene expression during plant growth and development. However, little is known about their regulatory roles in response to stressful environments in birch (Betula platyphylla). Here, we characterized and further explored miRNAs from osmotic- and salt-stressed birch. Our analysis revealed a total of 190 microRNA (miRNA) sequences, which were classified into 180 conserved miRNAs and 10 predicted novel miRNAs based on sequence homology. Furthermore, we identified Bp-miR408a under osmotic and salt stress and elucidated its role in osmotic and salt stress responses in birch. Notably, under osmotic and salt stress, Bp-miR408a contributed to osmotic and salt tolerance sensitivity by mediating various physiological changes, such as increases in reactive oxygen species accumulation, osmoregulatory substance contents and Na+ accumulation. Additionally, molecular analysis provided evidence of the in vivo targeting of BpBCP1 (blue copper protein) transcripts by Bp-miR408a. The overexpression of BpBCP1 in birch enhanced osmotic and salt tolerance by increasing the antioxidant enzyme activity, maintaining cellular ion homeostasis and decreasing lipid peroxidation and cell death. Thus, we reveal a Bp-miR408a-BpBCP1 regulatory module that mediates osmotic and salt stress responses in birch.

Pressure effect on the magnetism and crystal structure of magnetoelectric metal-organic framework [CH3NH3][Co(HCOO)3].

[CH3NH3][Co(HCOO)3] is the first perovskite-like metal-organic framework exhibiting spin-driven magnetoelectric effects. However, the high-pressure tuning effects on the magnetic properties and crystal structure of [CH3NH3][Co(HCOO)3] have not been studied. In this work, alongside ac magnetic susceptibility measurements, we investigate the magnetic transition temperature evolution under high pressure. Upon increasing the pressure from atmospheric pressure to 0.5 GPa, TN (15.2 K) remains almost unchanged. Continuing to compress the sample results in TN gradually decreasing to 14.8 K at 1.5 GPa. This may be due to pressure induced changes in the bond distance and bond angle of the O-C-O superexchange pathway. In addition, by using high pressure powder X-ray diffraction and Raman spectroscopy, we conducted in-depth research on the pressure dependence of the lattice parameters and Raman modes of [CH3NH3][Co(HCOO)3]. The increase in pressure gives rise to a phase transition from the orthorhombic Pnma to a monoclinic phase at approximately 6.13 GPa. Our study indicates that high pressure can profoundly alter the crystal structure and magnetic properties of perovskite type MOF materials, which could inspire new endeavors in exploring novel phenomena in compressed metal-organic frameworks.

Multifunctional Biodegradable Conductive Hydrogel Regulating Microenvironment for Stem Cell Therapy Enhances the Nerve Tissue Repair.

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.