Tissue-Specific Distribution and Maternal Transfer of Persistent Organic Halogenated Pollutants in Frogs.

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states.

While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin, cell-adhesive peptide, and carbon monoxide nanogenerators into acellular blood vessels.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy. However, the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation. To address this issue, we fabricated the covalent-organic framework (COF)-based carbon monoxide (CO) nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis. The cell-adhesive peptide LXW-7 could capture endothelial-forming cells (EFCs) to promote endothelialization, while the antithrombotic molecule heparin prevented thrombus formation. The reactive oxygen species (ROS)-triggered CO release suppressed the adhesion and activation of macrophages, leading to the reduction of ROS and inflammatory factors. As a result, the endothelial-to-mesenchymal transition (EndMT) triggered by inflammation was restricted, facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs. When transplanted in vivo, these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months. This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel.

Engineering myocardium has shown great clinal potential for repairing permanent myocardial injury. However, the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical use. We prepared a mixed gel containing fibrin (5 mg/ml) and collagen I (0.2 mg/ml) and verified that human umbilical vein endothelial cells (HUVECs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could form microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of fibrin. hiPSC-CMs and HUVECs in the mixed gel formed self-organized cell clusters, which were then cultured in different media using a three-phase approach. The successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of 1-2 mm. The tissue exhibited autonomous beats that occurred at a frequency similar to a normal human heart rate. The internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in vivo. In summary, we propose a simple method for constructing vascularized engineered myocardial tissue, through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation techniques. The constructed tissue has potential value for clinical use after preliminary evaluation.

Achieving Long-Lived Charge Separated State through Ultrafast Interfacial Hole Transfer in Redox Sites-Isolated CdS Nanorods for Enhanced Photocatalysis.

As opposed to natural photosynthesis, a significant challenge in a semiconductor-based photocatalyst is the limited hole extraction efficiency, which adversely affects solar-to-fuel efficiency. Recent studies have demonstrated that photocatalysts featuring spatially isolated dual catalytic oxidation/reduction sites can yield enhanced hole extraction efficiencies. However, the decay dynamics of excited states in such photocatalysts have not been explored. Here a ternary barbell-shaped CdS/MoS2 /Cu2 S heterostructure is prepared, comprising CdS nanorods (NRs) interfaced with MoS2 nanosheets at both ends and Cu2 S nanoparticles on the sidewall. By using transient absorption (TA) spectra, highly efficient charge separation within the CdS/MoS2 /Cu2 S heterostructure are identified. This is achieved through directed electron transfer to the MoS2 tips at a rate constant of >8.3 × 109 s-1 and rapid hole transfer to the Cu2 S nanoparticles on the sidewall at a rate of >6.1 × 1010 s-1 , leading to an exceptional overall charge transfer constant of 2.3 × 1011 s-1 in CdS/MoS2 /Cu2 S. The enhanced hole transfer efficiency results in a remarkably prolonged charge-separated state, facilitating efficient electron accumulation within the MoS2 tips. Consequently, the ternary CdS/MoS2 /Cu2 S heterostructure demonstrates a 22-fold enhancement in visible-light-driven H2 generation compare to pure CdS nanorods. This work highlights the significance of efficient hole extraction in enhancing the solar-to-H2 performance of semiconductor-based heterostructure.

Subcellular Nanobionic Liposome with High Zeta Potential Enhances Intravesical Adhesion and Drug Delivery.

The administration of drugs resident to counteract fluid washout has received considerable attention. However, the fabrication of a biocompatible system with adequate adhesion and tissue penetration capability remains challenging. This study presents a cell membrane-inspired carrier at the subcellular scale that facilitates interfacial adhesion and tissue penetration to improve drug delivery efficiency. Both chitosan oligosaccharide (COS) and oleic acid (OA) modified membranes exhibit a high affinity for interacting with the negatively charged glycosaminoglycan layer, demonstrating that the zeta potential of the carrier is the key to determining spontaneous penetration and accumulation within the bladder tissue. In vivo modeling has shown that a high surface charge significantly improves the retention of the drug carrier in the presence of urine washout. Possibly due to charge distribution, electric field gradients, and lipid membrane softening, the high positive surface charge enabled the carriers to penetrate the urinary bladder barrier and/or enter the cell interior. Overall, this study represents a practical and effective delivery strategy for tissue binders.

Programmed Release METTL3-14 Inhibitor Microneedle Protects Myocardial Function by Reducing Drp1 m6A Modification-Mediated Mitochondrial Fission.

M6A modification is an RNA-important processing event mediated by methyltransferases METTL3 and METTL14 and the demethylases. M6A dynamic changes after myocardial infarction (MI), involved in the massive loss of cardiomyocytes due to hypoxia, as well as the recruitment and activation of myofibroblasts. Balanced mitochondrial fusion and fission are essential to maintain intracardiac homeostasis and reduce poststress myocardial remodeling. Double-layer programmed drug release microneedle (DPDMN) breaks the limitations of existing therapeutic interventions in one period or one type of cells, and multitargeted cellular combination has more potential in MI therapy. By employing hypoxia-ischemic and TGF-ß1-induced fibrosis cell models, we found that METTL3-14 inhibition effectively decreased cardiomyocyte death through the reduction of mitochondrial fragmentation and inhibiting myofibrillar transformation. DPDMN treatment of MI in rat models showed improved cardiac function and decreased infarct size and fibrosis level, demonstrating its superior effectiveness. The DPDMN delivers METTL3 inhibitor swiftly in the early phase to rescue dying cardiomyocytes and slowly in the late phase to achieve long-term suppression of fibroblast over proliferation, collagen synthesis, and deposition. RIP assay and mechanistic investigation confirmed that METTL3 inhibition reduced the translation efficiency of Drp1 mRNA by 5'UTR m6A modification, thus decreasing the Drp1 protein level and mitochondrial fragment after hypoxic-ischemic injury. This project investigated the efficacy of DPDMNs-loaded METTL3 inhibitor in MI treatment and the downstream signaling pathway proteins, providing an experimental foundation for the translation of the utility, safety, and versatility of microneedle drug delivery for MI into clinical applications.

Preclinical evaluation of the safety and effectiveness of a new bioartificial cornea.

Cross-linking agents are frequently used to restore corneal properties after decellularization, and it is especially important to select an appropriate method to avoid excessive cross-linking. In addition, how to promote wound healing and how to improve scar formation require further investigation. To ensure the safety and efficacy of animal-derived products, we designed bioartificial corneas (BACs) according to the criteria for Class III medical devices. Our BACs do not require cross-linking agents and increase mechanical strength via self-cross-linking of aldehyde-modified hyaluronic acid (AHA) and carboxymethyl chitosan (CMC) on the surface of decellularized porcine corneas (DPCs). The results showed that the BACs had good biocompatibility and transparency, and the modification enhanced their antibacterial and anti-inflammatory properties in vitro. Preclinical animal studies showed that the BACs can rapidly regenerate the epithelium and restore vision within a month. After 3 months, the BACs were gradually filled with epithelial, stromal, and neuronal cells, and after 6 months, their transparency and histology were almost normal. In addition, side effects such as corneal neovascularization, conjunctival hyperemia, and ciliary body hyperemia rarely occur in vivo. Therefore, these BACs show promise for clinical application for the treatment of infectious corneal ulcers and as a temporary covering for corneal perforations to achieve the more time.

Biomimetic Antithrombotic Tissue-Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Herein, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen-gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming "harmful" substances into "beneficial" factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.

Long-Lived Photoacid-Doped Conducting Composites Induce Photocurrent for Efficient Wound Healing.

Electrical stimulation is an effective strategy for facilitating wound healing. However, it is hindered by unwieldy electrical systems. In this study, a light-powered dressing based on long-lived photoacid generator (PAG)-doped polyaniline composites is used, which can generate a photocurrent under visible light irradiation to interact with the endogenous electric field and facilitate skin growth. Light-controlled proton binding and dissociation result in oxidation and reduction of the polyaniline backbone, inducing charge transfer to generate a photocurrent. Due to the rapid intramolecular photoreaction of PAG, a long-lived proton-induced localized acidic environment is formed, which protects the wound from microbial infection. In summary, a simple and effective therapeutic strategy is introduced for light-powered and biocompatible wound dressings that show great potential for wound treatment.

A π-Conjugated Van der Waals Heterostructure Between Single-Atom Ni-Anchored Salphen-Based Covalent Organic Framework and Polymeric Carbon Nitride for High-Efficiency Interfacial Charge Separation.

Semiconductor-based heterostructures have exhibited great promise as a photocatalyst to convert solar energy into sustainable chemical fuels, however, their solar-to-fuel efficiency is largely restricted by insufficient interfacial charge separation and limited catalytically active sites. Here the integration of high-efficiency interfacial charge separation and sufficient single-atom metal active sites in a 2D van der Waals (vdW) heterostructure between ultrathin polymeric carbon nitride (p-CN) and Ni-containing Salphen-based covalent organic framework (Ni-COF) nanosheets is illustrated. The results reveal a NiN2 O2 chemical bonding in NiCOF nanosheets, leading to a highly separated single-atom Ni sites, which will function as the catalytically active sites to boost solar fuel production, as confirmed by X-ray absorption spectra and density functional theory calculations. Using ultrafast femtosecond transient adsorption (fs-TA) spectra, it shows that the vdW p-CN/Ni-COF heterostructure exhibits a faster decay lifetime of the exciton annihilation (τ = 18.3 ps) compared to that of neat p-CN (32.6 ps), illustrating an efficiently accelerated electron transfer across the vdW heterointerface from p-CN to Ni-COF, which thus allows more active electrons available to participate in the subsequent reduction reactions. The photocatalytic results offer a chemical fuel generation rate of 2.29 mmol g-1 h-1 for H2 and 6.2 µmol g-1 h-1 for CO, ≈127 and three times higher than that of neat p-CN, respectively. This work provides new insights into the construction of a π-conjugated vdW heterostructure on promoting interfacial charge separation for high-efficiency photocatalysis.

Sex-Specific Bioaccumulation, Maternal Transfer, and Tissue Distribution of Legacy and Emerging Per- and Polyfluoroalkyl Substances in Snakes (Enhydris chinensis) and the Impact of Pregnancy.

The effects of sex and pregnancy on the bioaccumulation and tissue distribution of legacy and emerging per- and polyfluoroalkyl substances (PFASs) in Chinese water snakes were investigated. The bioaccumulation factor of PFASs showed a positive correlation with their protein-water partition coefficients (log KPW), and steric hindrance effects were observed when the molecular volume was > 357 Å3. PFAS levels in females were significantly lower than those in males. The chemical composition of pregnant females was significantly different from that of non-pregnant females and males. The maternal transfer efficiencies of perfluorooctane sulfonic acid were higher than those of other PFASs, and a positive correlation between the maternal transfer potential and log KPW was observed for other PFASs. Tissues with high phospholipid content exhibited higher concentrations of ∑PFASs. Numerous physiological changes occurred in maternal organ systems during pregnancy, leading to the re-distribution of chemicals among different tissues. The change in tissue distribution of PFASs that are easily and not-so-easily maternally transferred was in the opposite direction. The extent of compound transfer from the liver to the egg determined tissue re-distribution during pregnancy.

π-Conjugated In-Plane Heterostructure Enables Long-Lived Shallow Trapping in Graphitic Carbon Nitride for Increased Photocatalytic Hydrogen Generation.

The relatively short-lived excited states, such as the nascent electron-hole pairs (excitons) and the shallow trapping states, in semiconductor-based photocatalysts produce an exceptionally high charge carrier recombination rate, dominating a low solar-to-fuel performance. Here, a π-conjugated in-plane heterostructure between graphitic carbon nitride (g-CN) and carbon rings (Crings ) (labeling g-CN/Crings ) is effectively synthesized from the thermolysis of melamine-citric acid aggregates via a microwave-assisted heating process. The g-CN/Crings in-plane heterostructure shows remarkably suppressed excited-state decay and increased charge carrier population in photocatalysis. Kinetics analysis from the femtosecond time-resolved transient absorption spectroscopy illustrates that the g-CN/Crings π-conjugated heterostructure produces slower exciton annihilation (τ1  = 7.9 ps) and longer shallow electron trapping (τ2  = 407.1 ps) than pristine g-CN (τ1  = 3.6 ps, τ2  = 264.1 ps) owing to Crings incorporation, both of which enable more photoinduced electrons to participate in the photocatalytic reactions, thereby realizing photoactivity enhancement. As a result, the photocatalytic activity exhibits an eightfold enhancement in visible-light-driven H2 generation. This work provides a viable route of constructing π-conjugated in-plane heterostructures to suppress the excited-state decay and improve the photocatalytic performance.

Surface valence regulation of cobalt-nickel foams for glucose oxidation-assisted water electrolysis.

Electrooxidation reactions of organic molecules that require a much lower overpotential are currently considered as promising alternatives to replace the oxygen evolution reaction (OER) in water electrolysis. Herein, an ultrafast oxygen plasma treatment is implemented to modify commercial cobalt-nickel foam (CNF) to regulate the high-valence Co3+ and Ni3+, rendering more active sites, faster reaction kinetics and enhanced response towards glucose. Compared to the OER, the overpotential of the plasma-treated CNF at 10 mA cm-2 was reduced to 133 mV via glucose electro-oxidation coupled with water splitting.

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy.

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor ß receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.

Arrays of Ag-nanoparticles decorated TiO2 nanotubes as reusable three-dimensional surface-enhanced Raman scattering substrates for molecule detection.

Three-dimensional surface-enhanced Raman scattering (SERS) substrates usually provide more hot spots in the excitation light beam and higher sensitivity when compared with the two-dimensional counterpart. Here a simple approach is presented for the fabrication of arrays of Ag-nanoparticles decorated TiO2 nanotubes. Arrays of ZnO nanorods were fabricated in advance by a hydrothermal method. Then TiO2 nanotube arrays were achieved by immersing the arrays of ZnO nanorods in an aqueous solution of (NH4)2TiF6 for 1.5 h. Vertically aligned TiO2 nanotube arrays were modified with dense Ag nanoparticles by Ag mirror reaction. High density of Ag nanoparticles decorated on the fabricated TiO2 nanotubes provide plenty of hotspots for Raman enhancement. In addition, the fabricated array of Ag nanoparticles modified TiO2 nanotubes can serve as a reusable SERS substrate because of the photocatalytic activity of the TiO2 nanotubes. The SERS substrate adsorbed with analyte molecules can realize self-cleaning in deionized water after UV irradiation for 2.5 h. The sensitivity of the fabricated SERS substrate was investigated by the detection of organic dye molecules. The detectable concentration limits of rhodamine 6G (R6G), malachite green (MG) and methylene blue (MB) were found to be 10-12 M, 10-9 M and 10-8 M, respectively. The enhancement factor (EF) of the three-dimensional SERS substrate was estimated to be as high as ∼1.4×108. Therefore, the prepared Ag nanoparticles modified TiO2 nanotube arrays have promising potentials to be applied to rapid and trace SERS detection of organic chemicals.

Underwater instant adhesion mechanism of self-assembled amphiphilic hemostatic granular hydrogel from Andrias davidianus skin secretion.

The widespread use of biological tissue adhesives for tissue repair is limited by their weak adhesion in a wet environment. Herein, we report the wet adhesion mechanism of a dry granular natural bioadhesive from Andrias davidianus skin secretion (ADS). Once contacting water, ADS granules self-assemble to form a hydrophobic hydrogel strongly bonding to wet substrates in seconds. ADS showed higher shear adhesion than current commercial tissue adhesives and an impressive 72-h underwater adhesion strength of ∼47kPa on porcine skin tissue. The assembled hydrogel in water maintained a dissipation energy of ∼8 kJ/m3, comparable to the work density of muscle, exhibiting its robustness. Unlike catechol adhesion mechanism, ADS wet adhesion mechanism is attributed to water absorption by granules, and the unique equilibrium of protein hydrophobicity, hydrogen bonding, and ionic complexation. The in vivo adhesion study demonstrated its excellent wet adhesion and hemostasis performance in a rat hepatic and cardiac hemorrhage model.

Programming of Regulatory T Cells In Situ for Nerve Regeneration and Long-Term Patency of Vascular Grafts.

Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.

Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury.

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.

Harnessing Oxidative Microenvironment for In Vivo Synthesis of Subcellular Conductive Polymer Microesicles Enhances Nerve Reconstruction.

Conductive polymers (CPs) are promising biomaterials to address signal connection at biointerfaces for tissue regeneration. However, regulating material microstructure at the subcellular scale to provide a more seamless interface between conductive substrates and cells remains a great challenge. Here, we demonstrate that chemical factors and enzyme-carried subcellular structures at lesion site provide a natural bioreactor to self-assemble conductive microvesicles (CMVs) for improving bioelectrical signal reconstruction. The synthesized CMVs contribute to the electrical conduction of the injured nerve in the early stage. Moreover, CMVs are eventually expelled via lymphatic capillary to minimize space-occupying and chronic inflammation. Therefore, we provide a prototype to integrate specific physiological microenvironments and polymer chemistry to manufacture subcellular functional materials with self-adaptive interface in vivo for biomedical applications.