Silk-protein-based gradient hydrogels with multimode reprogrammable shape changes for biointegrated devices.

Biocompatible and morphable hydrogels capable of multimode reprogrammable, and adaptive shape changes are potentially useful for diverse biomedical applications. However, existing morphable systems often rely on complicated structural designs involving cumbersome and energy-intensive fabrication processes. Here, we report a simple electric-field-activated protein network migration strategy to reversibly program silk-protein hydrogels with controllable and reprogrammable complex shape transformations. The application of a low electric field enables the convergence of net negatively charged protein cross-linking networks toward the anode (isoelectric point plane) due to the pH gradient generated in the process, facilitating the formation of a gradient network structure and systems suitable for three-dimensional shape change. These tunable protein networks can be reprogrammed or permanently fixed by control of the polymorphic transitions. We show that these morphing hydrogels are capable of conformally interfacing with biological tissues by programming the shape changes and a bimorph structure consisting of aligned carbon nanotube multilayers and the silk hydrogels was assembled to illustrate utility as an implantable bioelectronic device for localized low-voltage electrical stimulation of the sciatic nerve in a rabbit.

Long-term annual mapping and spatial-temporal dynamic analysis of winter wheat in Shandong Province based on spatial-temporal data fusion (2000-2022).

Winter wheat, as one of the world's key staple crops, plays a crucial role in ensuring food security and shaping international food trade policies. However, there has been a relative scarcity of high-resolution, long time-series winter wheat maps over the past few decades. This study utilized Landsat and Sentinel-2 data to produce maps depicting winter wheat distribution in Google Earth Engine (GEE). We further analyzed the comprehensive spatial-temporal dynamics of winter wheat cultivation in Shandong Province, China. The gap filling and Savitzky-Golay filter method (GF-SG) was applied to address temporal discontinuities in the Landsat NDVI (Normalized Difference Vegetation Index) time series. Six features based on phenological characteristics were used to distinguish winter wheat from other land cover types. The resulting maps spanned from 2000 to 2022, featuring a 30-m resolution from 2000 to 2017 and an improved 10-m resolution from 2018 to 2022. The overall accuracy of these maps ranged from 80.5 to 93.3%, with Kappa coefficients ranging from 71.3 to 909% and F1 scores from 84.2 to 96.9%. Over the analyzed period, the area dedicated to winter wheat cultivation experienced a decline from 2000 to 2011. However, a notable shift occurred with an increase in winter wheat acreage observed from 2014 to 2017 and a subsequent rise from 2018 to 2022. This research highlights the viability of using satellite observation data for the long-term mapping and monitoring of winter wheat. The proposed methodology has long-term implications for extending this mapping and monitoring approach to other similar areas.

Regulatory Effects of Gradient Microtopographies on Synapse Formation and Neurite Growth in Hippocampal Neurons.

Among approaches aiming toward functional nervous system restoration, those implementing microfabrication techniques allow the manufacture of platforms with distinct geometry where neurons can develop and be guided to form patterned connections in vitro. The interplay between neuronal development and the microenvironment, shaped by the physical limitations, remains largely unknown. Therefore, it is crucial to have an efficient way to quantify neuronal morphological changes induced by physical or contact guidance of the microenvironment. In this study, we first devise and assess a method to prepare anisotropic, gradient poly(dimethylsiloxane) micro-ridge/groove arrays featuring variable local pattern width. We then demonstrate the ability of this single substrate to simultaneously profile the morphologcial and synaptic connectivity changes of primary cultured hippocampal neurons reacting to variable physical conditons, throughout neurodevelopment, in vitro. The gradient microtopography enhanced adhesion within microgrooves, increasing soma density with decreasing pattern width. Decreasing pattern width also reduced dendritic arborization and increased preferential axon growth. Finally, decreasing pattern geometry inhibited presynaptic puncta architecture. Collectively, a method to examine structural development and connectivity in response to physical stimuli is established, and potentially provides insight into microfabricated geometries which promote neural regeneration and repair.

Brain-Targeted Dual Site-Selective Functionalized Poly(ß-Amino Esters) Delivery Platform for Nerve Regeneration.

Brain injuries are devastating central nervous system diseases, resulting in cognitive, motor, and sensory dysfunctions. However, clinical therapeutic options are still limited for brain injuries, indicating an urgent need to investigate new therapies. Furthermore, the efficient delivery of therapeutics across the blood-brain barrier (BBB) to the brain is a serious problem. In this study, a facile strategy of dual site-selective functionalized (DSSF) poly(ß-amino esters) was developed using bio-orthogonal chemistry for promoting brain nerve regeneration. Fluorescence colocalization studies demonstrated that these proton-sponge DSSF poly(ß-amino esters) targeted mitochondria through electrostatic interactions. More importantly, this delivery system could effectively accumulate in the injured brain sites and accelerate the recovery of the injured brain. Finally, this DSSF poly(ß-amino esters) platform may provide a new methodology for the construction of dual regioselective carriers in protein/peptide delivery and tissue engineering.

A comprehensive method to increase yield and narrow the yield gap of winter wheat for sustainable intensification.

BACKGROUND: The agricultural production system is facing increasing demand pressure and environmental pressure. Green and efficient production methods are urgently needed in order to further enhance the yield of winter wheat and reduce the negative impact on the environment. Here, we analyzed the potential yield and yield gap of winter wheat in Shandong Province of China from 1981 to 2009. Meanwhile, we specified the effects of sowing time, irrigation and fertilization scheme, and variety characteristics on winter wheat. RESULTS: In the past 29 years, the yield gap in most areas of Shandong has become smaller, because the actual yield has increased and the potential yield has changed little under the background of climate change. In addition, it is found that delaying sowing date is beneficial to increase yield by helping winter wheat avoid adverse climate conditions. Also, an irrigation amount of 240 mm and nitrogen application amount of 180-210 kg ha-1 are best to maintain high yield, high resource utilization rate and low environmental pollution in this area. These suggested levels are lower than those currently used by many local farmers. Wheat varieties with longer grain-filling period and photoperiod response, higher grain-filling rate and grain weight were more adaptable to climate change. CONCLUSION: Improving agronomic management measures can significantly increase the yield of winter wheat and narrow the yield gap. This study can provide valuable information for improving the production potential of winter wheat, and for reducing the damage of agricultural activities to the environment. © 2022 Society of Chemical Industry.

Smartphone-Based Electrochemical Potentiostat Detection System Using PEDOT: PSS/Chitosan/Graphene Modified Screen-Printed Electrodes for Dopamine Detection.

In this work, a smartphone-based electrochemical detection system was designed and developed for rapid and real-time detection of dopamine (DA). The system included a screen-printed electrode (SPE) used as a sensor, a hand-held electrochemical potentiostat and a smart phone with a specially designed app. During the detection period, the SPEs modified with poly(3,4-ethylenedioxythiophene) (PEDOT), chitosan (CS) and graphene (G) were used to convert and amplify the electrochemical reaction signals. The electrochemical potentiostat was used to generate excitation electrical signals and collect the electrical signals converted from the sensor. The smartphone-connected to the detector via Bluetooth-was used to control the detector for tests, further process the uploaded data, and plot graphs in real time. Experimental results showed that the self-designed sensing system could be employed for highly selective detection of DA in the presence of interfering substances such as ascorbic acid (AA) and uric acid (UA). CV was carried out to characterize the electrochemical properties of the modified SPEs and the electrochemical behaviors of DA on the modified SPEs. Finally, according to the analysis of DPV responses of DA, the system could detect DA with a detection sensitivity of 0.52 ± 0.01 µA/µM and a limit of detection of 0.29 µM in the linear range of DA concentrations from 0.05 to 70 µM.

Measuring spatial accessibility to healthcare services with constraint of administrative boundary: a case study of Yanqing District, Beijing, China.

BACKGROUND: The two-step floating catchment area (2SFCA) method, which is one of the most widely used methods for measuring healthcare spatial accessibility, defines the catchment area of each facility as the area within a certain distance from the facility. However, in some cases, the service utilization behavior is constrained by administrative boundaries, therefore the definition of catchment area within a certain distance may be inappropriate. METHODS: In this study, we aim to propose a modification of the 2SFCA method for measuring spatial accessibility to healthcare services in a system constrained by administrative boundaries. The proposed method defines the catchment areas of healthcare facilities within certain administrative units. The method is applied in a case study of the healthcare services in Yanqing District of Beijing, China. Three types of healthcare facilities, including general hospitals, community healthcare centers and stations, are included. RESULTS: Based on the sensitivity analysis of the distance-decay parameter ß, result of the ß = 1 scenario is relatively appropriate and is utilized for further analysis. The difference between spatial accessibility with or without constraint of administrative boundary is relatively significant. The results of the proposed model show that the village-level spatial accessibility to healthcare services shows a significant disparity, and the uneven distribution of general hospitals is the main cause. CONCLUSIONS: The constraint of administrative boundary has a significant impact on healthcare accessibility, which verifies the validity of the modification proposed by this study in empirical studies. The empirical results also lead to policy recommendations to improve healthcare equity in the study area. At the town-level, the improvement of equity in healthcare accessibility could be achieved in two ways. First, the sizes of community healthcare centers in towns with small accessibility scores should be expanded. Second, new general hospitals can be built in the eastern part of Yanqing District. Within each town, to improve the equity in healthcare accessibility, community healthcare stations should be expanded or newly built in the periphery villages.

Spatial accessibility to healthcare services in Shenzhen, China: improving the multi-modal two-step floating catchment area method by estimating travel time via online map APIs.

BACKGROUND: Shenzhen has rapidly grown into a megacity in the recent decades. It is a challenging task for the Shenzhen government to provide sufficient healthcare services. The spatial configuration of healthcare services can influence the convenience for the consumers to obtain healthcare services. Spatial accessibility has been widely adopted as a scientific measurement for evaluating the rationality of the spatial configuration of healthcare services. METHODS: The multi-modal two-step floating catchment area (2SFCA) method is an important advance in the field of healthcare accessibility modelling, which enables the simultaneous assessment of spatial accessibility via multiple transport modes. This study further develops the multi-modal 2SFCA method by introducing online map APIs to improve the estimation of travel time by public transit or by car respectively. RESULTS: As the results show, the distribution of healthcare accessibility by multi-modal 2SFCA shows significant spatial disparity. Moreover, by dividing the multi-modal accessibility into car-mode and transit-mode accessibility, this study discovers that the transit-mode subgroup is disadvantaged in the competition for healthcare services with the car-mode subgroup. The disparity in transit-mode accessibility is the main reason of the uneven pattern of healthcare accessibility in Shenzhen. CONCLUSIONS: The findings suggest improving the public transit conditions for accessing healthcare services to reduce the disparity of healthcare accessibility. More healthcare services should be allocated in the eastern and western Shenzhen, especially sub-districts in Dapeng District and western Bao'an District. As these findings cannot be drawn by the traditional single-modal 2SFCA method, the advantage of the multi-modal 2SFCA method is significant to both healthcare studies and healthcare system planning.

Mulberroside A protects against ischemic impairment in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion.

Mulberroside A is a natural polyhydroxylated stilbene compound present at relatively high abundance in the roots and twigs of Morus alba L. It is known for its nephroprotective, hypoglycemic, and antidiabetic effects. Because its metabolite, oxyresveratrol, possessed purported anti-inflammatory and neuroprotective effects, we proposed that mulberroside A may elicit neuroprotective effects that can be used in the treatment of brain ischemic injury. Therefore, we decided to investigate the pharmacological properties of mulberroside A in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion (OGD/R), evaluating its ability to counteract the hypoxia-ischemia impairment. The results showed that mulberroside A elicited neuroprotective effects comparable to nimodipine. The mechanistic studies showed that mulberroside A decreased the expressions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 and inhibited the activation of NALP3, caspase-1, and nuclear factor-κB and the phosphorylation of extracellular signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38, exhibiting anti-inflammatory antiapoptotic effects. Our results also further demonstrate that the proinflammatory cytokines of IL-1ß, IL-6, and TNF-α are promising targets for treatment of cerebral ischemic injury. Although further investigation is required for its development, all of these findings led us to speculate that mulberroside A is a candidate for the treatment of ischemic stroke, which would act as a multifactorial neuroprotectant.

Research of smooth muscle cells response to fluid flow shear stress by hyaluronic acid micro-pattern on a titanium surface.

The morphology of vascular smooth muscle cells (SMCs) in the normal physiological state depends on cytoskeletal distribution and topology beneath, and presents vertical to the direction of blood flow shear stress (FFSS) although SMCs physiologically are not directly exposed to the shear conditions of blood flow. However, this condition is relevant for arteriosclerotic plaques and the sites of a vascular stent, and little of this condition in vitro has been studied and reported till now. It is unclear what will happen to SMC morphology, phenotype and function when the direction of the blood flow changed. In this paper, the distribution of SMCs in a specific area on Ti surface was regulated by micro-strips of hyaluronic acid (HA). Cell morphology depended on the distribution of the cytoskeleton extending along the micrographic direction. Simulated vascular FFSS was perpendicular or parallel to the direction of the cytoskeleton distribution. Based on investigating the morphology, apoptotic number, phenotypes and functional factors of SMCs, it was obtained that SMCs of vertical groups showed more apoptosis, expressed more contractile types and secreted less TGF-ß1 factor compared with SMCs of parallel groups, the number of ECs cultured by medium from SMCs of parallel groups was larger than vertical groups. This study could help to understand the effect of direction change of FFSS on patterned SMC morphology, phenotype and function.

Cell culture on suspended fiber for tissue regeneration: A review.

Cell culturing is a cornerstone of tissue engineering, playing a crucial role in tissue regeneration, drug screening, and the study of disease mechanisms. Among various culturing techniques, 3D culture systems, particularly those utilizing suspended fiber scaffolds, offer a more physiologically relevant environment than traditional 2D monolayer cultures. These 3D scaffolds enhance cell growth, differentiation, and proliferation by mimicking the in vivo cellular milieu. This review focuses on the critical role of suspended fiber scaffolds in tissue engineering. We compare the effectiveness of 3D suspended fiber scaffolds with 2D culture systems, discussing their respective benefits and limitations in the context of tissue regeneration. Furthermore, we explore the preparation methods of suspended fiber scaffolds and their potential applications. The review concludes by considering future research directions for optimizing suspended fiber scaffolds to address specific challenges in tissue regeneration, underscoring their significant promise in advancing tissue engineering and regenerative medicine.

Application of magnetism in tissue regeneration: recent progress and future prospects.

Tissue regeneration is a hot topic in the field of biomedical research in this century. Material composition, surface topology, light, ultrasonic, electric field and magnetic fields (MFs) all have important effects on the regeneration process. Among them, MFs can provide nearly non-invasive signal transmission within biological tissues, and magnetic materials can convert MFs into a series of signals related to biological processes, such as mechanical force, magnetic heat, drug release, etc. By adjusting the MFs and magnetic materials, desired cellular or molecular-level responses can be achieved to promote better tissue regeneration. This review summarizes the definition, classification and latest progress of MFs and magnetic materials in tissue engineering. It also explores the differences and potential applications of MFs in different tissue cells, aiming to connect the applications of magnetism in various subfields of tissue engineering and provide new insights for the use of magnetism in tissue regeneration.

Anisotropic microtopography surface of chitosan scaffold regulating skin precursor-derived Schwann cells towards repair phenotype promotes neural regeneration.

For repairing peripheral nerve and spinal cord defects, biomaterial scaffold-based cell-therapy was emerged as an effective strategy, requiring the positive response of seed cells to biomaterial substrate and environment signals. Previous work highlighted that the imposed surface properties of scaffold could provide important guidance cues to adhered cells for polarization. However, the insufficiency of native Schwann cells and unclear cellular response mechanisms remained to be addressed. Given that, this study aimed to illuminate the micropatterned chitosan-film action on the rat skin precursor-derived Schwann cells (SKP-SCs). Chitosan-film with different ridge/groove size was fabricated and applied for the SKP-SCs induction. Results indicated that SKP-SCs cultured on 30 µm size microgroove surface showed better oriented alignment phenotype. Induced SKP-SCs presented similar genic phenotype as repair Schwann cells, increasing expression of c-Jun, neural cell adhesion molecule, and neurotrophic receptor p75. Moreover, SKP-SC-secretome was subjected to cytokine array GS67 assay, data indicated the regulation of paracrine phenotype, a panel of cytokines was verified up-regulated at secreted level and gene expression level in induced SKP-SCs. These up-regulated cytokines exhibit a series of promotive neural regeneration functions, including cell survival, cell migration, cell proliferation, angiogenesis, axon growth, and cellular organization etc. through bioinformatics analysis. Furthermore, the effectively polarized SKP-SCs-sourced secretome, promoted the proliferation and migration capacity of the primarily cultured native rat Schwann cells, and augmented neurites growth of the cultured motoneurons, as well as boosted axonal regrowth of the axotomy-injured motoneurons. Taken together, SKP-SCs obtained pro-neuroregeneration phenotype in adaptive response to the anisotropic topography surface of chitosan-film, displayed the oriented parallel growth, the transition towards repair Schwann cell genic phenotype, and the enhanced paracrine effect on neural regeneration. This study provided novel insights into the potency of anisotropic microtopography surface to Schwann-like cells phenotype regulation, that facilitating to provide promising engineered cell-scaffold in neural injury therapies.

Development of ovalbumin implants with different spatial configurations for treatment of peripheral nerve injury.

Peripheral nerve injury (PNI) seriously affects the health and life of patients, and is an urgent clinical problem that needs to be resolved. Nerve implants prepared from various biomaterials have played a positive role in PNI, but the effect should be further improved and thus new biomaterials is urgently needed. Ovalbumin (OVA) contains a variety of bioactive components, low immunogenicity, tolerance, antimicrobial activity, non-toxicity and biodegradability, and has the ability to promote wound healing, cell growth and antimicrobial properties. However, there are few studies on the application of OVA in neural tissue engineering. In this study, OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed by casting, electrospinning, and freeze-drying methods, respectively. The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity, and can promote vascularization, show good histocompatibility, without excessive inflammatory response and immunogenicity. The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells, while the in vivo results confirmed that OVA implants (the E5/70% and 20 kV 20 µL/min groups) could effectively regulate the growth of blood vessels, reduce the inflammatory response and promote the repair of subcutaneous nerve injury. Further on, the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α (TNF-α), phosphatidylinositide 3-kinases/protein kinase B (PI3K-Akt) signaling pathway, axon guidance, cellular adhesion junctions, and nerve regeneration in Schwann cells. The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.

Multifunctional double-network hydrogel with antibacterial and anti-inflammatory synergistic effects contributes to wound healing of bacterial infection.

Wound infection not only hinders the time sequence of tissue repair, but also may lead to serious complications. Multifunctional wound dressings with biocompatibility, excellent mechanical properties and antibacterial properties can promote wound healing during skin infection and reduce the use of antibiotics. In this study, a multifunctional dual-network antibacterial hydrogel was constructed based on the electrostatic interaction of two polyelectrolytes, hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and sodium alginate (SA). Attributing to the suitable physical crosslinking between HACC and SA, the hydrogel not only has good biocompatibility, mechanical property, but also has broad-spectrum antibacterial properties. In vivo results showed that the hydrogel could regulate M2 polarization, promote early vascular regeneration, and create a good microenvironment for wound healing. Therefore, this hydrogel is an effective multifunctional wound dressing. Consequently, we propose a novel hydrogel with combined elements to expedite the intricate repair of wound infection.

Convergent and divergent transcriptional reprogramming of motor and sensory neurons underlying response to peripheral nerve injury.

INTRODUCTION: Motor neurons differ from sensory neurons in aspects including origins and surrounding environment. Understanding the similarities and differences in molecular response to peripheral nerve injury (PNI) and regeneration between sensory and motor neurons is crucial for developing effective drug targets for CNS regeneration. However, genome-wide comparisons of molecular changes between sensory and motor neurons following PNI remains limited. OBJECTIVES: This study aims to investigate genome-wide convergence and divergence of injury response between sensory and motor neurons to identify novel drug targets for neural repair. METHODS: We analyzed two large-scale RNA-seq datasets of in situ captured sensory neurons (SNs) and motoneurons (MNs) upon PNI, retinal ganglion cells and spinal cord upon CNS injury. Additionally, we integrated these with other related single-cell level datasets. Bootstrap DESeq2 and WGCNA were used to detect and explore co-expression modules of differentially expressed genes (DEGs). RESULTS: We found that SNs and MNs exhibited similar injury states, but with a delayed response in MNs. We identified a conserved regeneration-associated module (cRAM) with 274 shared DEGs. Of which, 47% of DEGs could be changed in injured neurons supported by single-cell resolution datasets. We also identified some less-studied candidates in cRAM, including genes associated with transcription, ubiquitination (Rnf122), and neuron-immune cells cross-talk. Further in vitro experiments confirmed a novel role of Rnf122 in axon growth. Analysis of the top 10% of DEGs with a large divergence suggested that both extrinsic (e.g., immune microenvironment) and intrinsic factors (e.g., development) contributed to expression divergence between SNs and MNs following injury. CONCLUSIONS: This comprehensive analysis revealed convergent and divergent injury response genes in SNs and MNs, providing new insights into transcriptional reprogramming of sensory and motor neurons responding to axonal injury and subsequent regeneration. It also identified some novel regeneration-associated candidates that may facilitate the development of strategies for axon regeneration.

IKVAV functionalized oriented PCL/Fe3O4 scaffolds for magnetically modulating DRG growth behavior.

The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe3O4) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe3O4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness. The PCL/Fe3O4 scaffolds containing different Fe3O4 concentrations were free of cytotoxicity, indicating the good biocompatibility and low cytotoxicity of the scaffolds. The IKVAV-functionalized PCL/Fe3O4 scaffolds were able to guide and promote the directional extension of axons, the application of external magnetic field and the grafting of IKVAV peptides significantly further promoted the growth of DRGs and axons. The ELISA test results showed that the AP-10 F group scaffolds promoted the secretion of nerve growth factor (NGF) from DRG under a static magnetic field (SMF), thus promoting the growth and extension of axons. Importantly, the IKVAV-functionalized PCL/Fe3O4 scaffolds could significantly up-regulate the expression of Cntn2, PCNA, Sox10 and Isca1 genes related to adhesion, proliferation and magnetic receptor function under the stimulation of SMF. Therefore, IKVAV-functionalized PCL/Fe3O4 composite oriented scaffolds have potential applications in neural tissue engineering.

Correction: Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

[This corrects the article DOI: 10.1039/D4RA00793J.].

Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

Antibacterial hydrogels have gained considerable attention for soft tissue repair, particularly in preventing infections associated with wound healing. However, developing an antibacterial hydrogel that simultaneously possesses excellent cell affinity and controlled release of metal ions remains challenging. This study introduces an antibacterial hydrogel based on alginate modified with bisphosphonate, forming a coordination complex with magnesium ions. The hydrogel, through an interpenetrating network with silk fibroin, effectively controls the release of magnesium ions and enhances strain resistance. The Alg-Mg/SF hydrogel not only demonstrates outstanding biocompatibility and broad-spectrum antibacterial properties but also stimulates macrophages to secrete anti-inflammatory factors. This advanced Alg-Mg/SF hydrogel provides a convenient therapeutic approach for chronic wound management, showcasing its potential applications in wound healing and other relevant biomedical fields.

Biomimetic-inspired piezoelectric ovalbumin/BaTiO3 scaffolds synergizing with anisotropic topology for modulating Schwann cell and DRG behavior.

The treatment of peripheral nerve injury is a clinical challenge that tremendously affected the patients' health and life. Anisotropic topographies and electric cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, most studies just unilaterally emphasize the effect of sole topological- or electric- cue on nerve regeneration, while rarely considering the synergistic function of both cues simultaneously. In this study, a biomimetic-inspired piezoelectric topological ovalbumin/BaTiO3 scaffold that can provide non-invasive electrical stimulation in situ was constructed by combining piezoelectric BaTiO3 nanoparticles and surface microtopography. The results showed that the incorporation of piezoelectric nanoparticles could improve the mechanical properties of the scaffolds, and the piezoelectric output of the scaffolds after polarization was significantly increased. Biological evaluation revealed that the piezoelectric topological scaffolds could regulate the orientation growth of SCs, promote axon elongation of DRG, and upregulate the genes expression referring to myelination and axon growth, thus rapidly integrated chemical-mechanical signals and transmitted them for effectively promoting neuronal myelination, which was closely related to peripheral neurogenesis. The study suggests that the anisotropic surface topology combined with non-invasive electronic stimulation of the ovalbumin/BaTiO3 scaffolds possess a promising application prospect in the repair and regeneration of peripheral nerve injury.