Chiral Supramolecular Nanofibers Regulated Tumor-Derived Exosomes Secretion for Constructing an Anti-Tumor Extracellular Microenvironment.

Tumor-derived exosomes (TDEs) induced extracellular microenvironment has recently been validated to be critical for tumor progression and metastasis, however, remodeling it for oncotherapy still remains a major challenge due to difficulty in regulation of TDEs secretion. Herein, the supramolecular chiral nanofibers, composed of L/D -phenylalanine derivates (L/D-Phe) and linear hyaluronic acid (HA), are successfully employed to construct TDEs induced anti-tumor extracellular microenvironment. The left-handed L-Phe @HA nanofibers significantly inhibit TDEs secretion into extracellular microenvironment, which results in suppression of tumor proliferation and metastasis in vitro and vivo. Biological assays and theoretical modeling reveal that these results are mainly attributed to strong adsorption of the key exosomes transporters (Ras-related protein Rab-27A and synaptosome-associated protein 23) on left-handed L-Phe @HA nanofibers via enhanced stereoselective interaction, leading to degradation and phosphorylated dropping of exosomes transporters. Subsequently, transfer function of exosomes transporters is limited, which causes remarkable inhibition of TDEs secretion. These findings provide a promising novel insight of chiral functional materials to establish an anti-tumor extracellular microenvironment via regulation of TDEs secretion.

NDI based C2-symmetric Chiral Supramolecular Hydrogels Towards Enhanced Conductivity.

To comprehend the significance of improved conductive properties in C2-symmetric hydrogels, it is vital to investigate how non-gelating achiral functional group isomers influence the conductivity of such supramolecular hydrogels, whereas understanding the major driving forces behind this regulatory process is first and foremost. Herein, we report a hydrogel system containing tryptophan-conjugated NDI as the backbone (L/D-NTrp), enabling effective supramolecular assembly with the bipyridyl functional group isomers. This co-assembly behavior results in materials with exceptional mechanical properties and high conductivities, surpassing most previously reported C2-symmetrical hydrogels, as well as the ability to form controlled morphologies. Notably, the co-hydrogels displayed an eight-fold increase in mechanical strength, making them more robust and resistant to deformation compared to the original gel. Additionally, all hydrogels exhibited favorable electrical conductivity, with the co-assembled hydrogels showcasing notable performance, making them a promising candidate for use in electronic devices and sensors. This report lays the foundation for further investigation into the properties and potential applications of L/D-NTrp compound in the range of fields, including drug delivery, tissue engineering, and electronics.

Clinical features and outcomes of children's interstitial lung disease accompanied with connective tissue disease: A prospective cohort study.

BACKGROUND: Medical complexity of childhood interstitial lung disease (chILD) with connective tissue disease (CTD) poses a considerable challenge to pediatricians. METHODS: Clinical characteristics, laboratory findings, pulmonary function tests (PFTs), treatments and outcomes obtained for patients with CTD-chILD were analyzed in a prospective study. RESULTS: Patients' median age at diagnosis was 7 years old. About 29.4% (15/51) suffered rapidly progressive childhood ILD (RP-chILD) with a high mortality rate (33.3%, 5/15), and the incidence of RP-chILD in juvenile idiopathic inflammatory myopathies was as high as 41.6% and the mortality rate was 30% (3/10). More than 70% patients had decreased diffusion capacity. The mean interval from symptoms-onset to diagnosis was 11.3 months. Compared to chILD with known CTD, the chILD proceeded CTD had a longer diagnosis interval, higher mortality, hospital stays and costs (P < 0.05). Lung imaging (33.3%) and lung function (72.7%) were partially reversible. The average survival time was 68.6 months. Cox univariate analysis showed that HRCT score ≥3, experiencing RP-chILD, cyanosis, acute respiratory distress syndrome (ARDS) and CD4 T cell <200 were significant predictors of death for chILD, whereas Cox multivariate analysis showed that ARDS was significant predictor of death for CTD-chILD, while IVIG support combined with corticosteroids and immunosuppressants was a protective factor. CONCLUSIONS: Care providers should conduct an assessment for CTD in chILD as a longer interval between the diagnosis of chILD and the CTD is associated with increased mortality. Complications as ARDS predict poor outcome in CTD-chILD, while IVIG support combined with corticosteroids and immunosuppressants is a protective factor.

Enhancing the Cycle Performance of Lithium-Sulfur Batteries by Coating the Separator with a Cation-Selective Polymer Layer.

Lithium-sulfur batteries are believed to possess the feasibility to power electric vehicles in the future ascribed to the competitive energy density. However, soluble polysulfides continuously shuttle between the sulfur electrode and lithium anode across the separator, which dramatically impairs the battery's capacity. Herein, the surface of a polypropylene separator (PP film) is successfully modified with a delicately designed cation-selective polymer layer to suppress the transport of polysulfides. In principle, since bis-sulfonimide anions groups on the backbone of the polymer are immobilized, only cations can pass through the polymer layer. Furthermore, plenty of ethoxy chains in the polymer can facilitate lithium-ion mobility. Consequently, in addition to obstructing the movement of negatively charged polysulfides by the electrostatic repulsive force of fixed anions, the coated multi-functional layer on the PP film also guarantees the smooth conduction of lithium ions. The investigations demonstrate that the battery with the pristine PP film only delivers 228.5 mAh g-1 after 300 cycles at 2 C with a high capacity fading rate of 60.9 %. By contrast, the polymer-coated sample can release 409.4 mAh g-1 under the identical test condition and the capacity fading rate sharply declines to 43.2 %, illustrating superior cycle performance.

FBXO7, a tumor suppressor in endometrial carcinoma, suppresses INF2-associated mitochondrial division.

Endometrial carcinoma (ECa) is the most common malignant gynecological cancer, with an increased incidence and fatality rate worldwide, while the pathogenesis is still largely unknown. In this study, we confirmed that FBXO7, a gene coding FBXO7 E3 ubiquitin ligase, is significantly downregulated and mutated (5.87%; 31/528) in ECa specimens, and the abnormal low expression and mutations of FBXO7 are associated with the occurrence of ECa. We also identify the excessive expression of INF2 protein, a key factor that triggers mitochondrial division by recruiting the DRP1 protein, and the elevated INF2 protein is significantly negatively correlated with the low FBXO7 protein in ECa specimens. Mechanistically, FBXO7 restrains ECa through inhibiting INF2-associated mitochondrial division via FBXO7-mediated ubiquitination and degradation of INF2. Moreover, we found that ECa-associated FBXO7 mutants are defective in the ubiquitination and degradation of INF2, promoting ECa cells proliferation, migration and apoptosis inhibition via inducing mitochondrial hyper-division. In addition, we found that it could reverse FBXO7 deletion or ECa-associated FBXO7 mutants-induced proliferation, migration, apoptosis inhibition and mitochondrial hyper-division of ECa cells by INF2 or DNM1L knockdown, or DRP1 inhibitor Mdivi-1. In summary, our study shows that FBXO7 acts as a novel tumor suppressor in ECa by inhibiting INF2-DRP1 axis-associated mitochondrial division through the ubiquitination and degradation of INF2 while the effect is destroyed by ECa-associated FBXO7 and INF2 mutants, highlights the key role of FBXO7-INF2-DRP1 axis in ECa tumorigenesis and provides a new viewpoint to treat ECa patients with FBXO7 deletion or mutations by targeting INF2-DRP1 axis-associated mitochondrial division.

Molecular Polarizability Regulated Piezoelectricity of Organic Materials from Single-Molecular Level.

Although molecular piezoelectric materials are ideal constituents for next-generation electronic microdevices, their weak piezoelectric coefficients which restrict their practical applications need to be enhanced by some strategies. Herein, a series of d-phenylalanine derivatives are synthesized and an increased molecular piezoelectric coefficient of their assemblies is achieved by acid doping. The acid doping can increase the asymmetric distribution of charges in the molecules and in turn molecular polarizability, leading to the enhanced molecular piezoelectricity of assemblies. The effective piezoelectric coefficients can be promoted up to 38.5 pm V-1 and four times those without doping, which is also higher than those obtained by the reported methods. Moreover, the piezoelectric energy harvesters can generate voltage up to 3.4 V and current up to 80 nA. This practical strategy can enhance piezoelectric coefficients without varying the crystal structures of the assemblies, which may inspire future molecular design of organic functional materials.

Spatial Confinement Modulates Macrophage Response in Microporous Annealed Particle (MAP) Scaffolds.

Macrophages are essential in the initiation, maintenance, and transition of inflammatory processes such as foreign body response and wound healing. Mounting evidence suggests that physical factors also modulate macrophage activation. 2D in vitro systems demonstrate that constraining macrophages to small areas or channels modulates their phenotypes and changes their responses to known inflammatory agents such as lipopolysaccharide. However, how dimensionality and pore size affect macrophage phenotype is less explored. In this work, the change in macrophage M1/M2 polarization when confined in microporous annealed particle (MAP) scaffolds is studied. Particles sizes (40, 70, and 130 µm) are selected using outputs from software LOVAMAP that analyzes the characteristics of 3D pores in MAP gels. As the size of building block particle correlates with pore size inside the scaffolds, the three  types of scaffold allow us to study how the degree of spatial confinement modulates the behavior of embedded macrophages. Spatially confining macrophages in scaffolds with pore size on the scale of cells leads to a reduced level of the inflammatory response, which is correlated with a change in cell morphology and motility.

Recent progress in exosome research: isolation, characterization and clinical applications.

Exosomes, a kind of nano-vesicles released by various cell types, carry a variety of "cargos" including proteins, RNAs, DNAs and lipids. There is substantial evidence that exosomes are involved in intercellular communication by exchanging "cargos" among cells and play important roles in cancer development. Because of the different expressions of "cargos" carried by exosomes in biological fluids under physiological and pathological conditions, exosomes have the potential as a minimally invasive method of liquid biopsy for cancer diagnosis and prognosis. In addition, due to their good biocompatibility, safety, biodistribution and low immunogenicity, exosomes also have potential applications in the development of promising cancer treatment methods. In this review, we summarize the recent progress in the isolation and characterization techniques of exosomes. Moreover, we review the biological functions of exosomes in regulating tumor metastasis, drug resistance and immune regulation during cancer development and outline the applications of exosomes in cancer therapy.

Pomalidomide enhances the maturation of dendritic cells derived from healthy donors and multiple myeloma patients.

Objective: To explore the effect of pomalidomide on the maturation of monocyte-derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients. Methods: MoDCs were generated by the incubation of monocytes from peripheral blood mononuclear cells (PBMCs) for 7 days in a medium consisting of 800 U/ml granulocyte-macrophage colony stimulating factor (GM-CSF), 500 U/ml interleukin-4 (IL-4), RPMI 1,640 medium, 5% human serum, 100 U/ml penicillin and 0.1 mg/ml streptomycin. Meanwhile, the incubation system was administrated with 10 µM pomalidomide or 1 × PBS as the control group. On the eighth day, cells were harvested and analyzed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as moDCs in the FACS analyzing system. After that, the expression of CD40 and HLA-DR on moDCs was analyzed. Meanwhile, the supernatant from the incubation system was evaluated for the secretion of cytokines interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein 1α (MIP-1α) by enzyme-linked immunosorbent assay (ELISA). Results: When analyzing all the HD-moDCs together (n = 15), pomalidomide significantly increased the mean fluorescence intensity (MFI) of CD40 expression and HLA-DR expression on moDCs compared with the control group (p = 0.003, p = 0.040). Meanwhile, the proportion of CD40+ moDCs and HLA-DR+ moDCs in total moDCs was significantly higher in the pomalidomide group than in the control group (p = 0.008, p = 0.032). When analyzing all MM patient-moDCs together (n = 11), pomalidomide significantly increased the MFI of CD40 expression and HLA-DR expression on moDCs compared with the control group (p = 0.047, p = 0.006). Meanwhile, the proportion of HLA-DR+ moDCs in total DCs was significantly higher in the pomalidomide group than in the control group (p < 0.001). Moreover, HD-moDCs (n = 8) treated with pomalidomide secreted 192% IL-12, 110% TNF-α, and 112% MIP-1α of the untreated moDCs (p = 0.020, p = 0.006, p = 0.055). However, when analyzing MM patient-moDCs (n = 10) together, the secretion of IL-12, TNF-α and MIP-1α from moDCs showed no significant difference between the pomalidomide group and the control group (p = 0.458, p = 0.377, p = 0.248). Conclusion: In vitro, 10 µM pomalidomide enhances the maturation of moDCs derived from both HDs and MM patients. Pomalidomide shows potential to be applied as a DC adjuvant for DC-based immunotherapy, such as the DC vaccine and DC cell therapy in MM.

Research on the Effect of Freeze-Thaw Cycles at Different Temperatures on the Pore Structure of Water-Saturated Coal Samples.

To study the pore structure transformation of coal at different temperatures, freeze-thaw cycle experiments at different temperature intervals (20 to -20 °C, 20 to -40 °C, 20 to -196 °C) were carried out. The low-field nuclear magnetic resonance equipment was used to characterize the peak area, pore size distribution, and pore number of each group of coal samples. The pore transformation effect of coal samples at different temperature intervals was compared, and the change characteristics of the pore structure of coal samples under the freeze-thaw action were explored. The research shows that the freeze-thaw cycles at different freezing temperature intervals have obvious differences in the effect of coal pore transformation. The area of each peak spectrum in the T 2 distribution curve of coal samples increased significantly under the action of freeze-thaw cycles in different freezing temperature intervals. The increased value of the number of mesopores and macropores shows the phenomenon of "first increase and then decrease" with the increase of the temperature difference. There is a quadratic function relationship between the temperature difference in the freezing temperature interval and the proportion change rate of the adsorption pore or seepage pore. The continuous increase of the temperature difference has a certain marginal effect on the proportion change rate of seepage pores and adsorption pores in coal.

[Effects of Dasatinib on the Maturation of Monocyte-Derived Dendritic Cells Derived from Healthy Donors and Chronic Myelogenous Leukemia Patients].

OBJECTIVE: To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively. RESULTS: The proportion of CD80+CD86+ cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group. CONCLUSION: For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.

Recent progress of dendritic cell-derived exosomes (Dex) as an anti-cancer nanovaccine.

Although cancer vaccines such as dendritic cell (DC) vaccines and peptide vaccines have become appealing and attractive anticancer immunotherapy options in recent decades, some obstacles have hindered their successful application in the clinical setting. The difficulties associated with the high cost of DC preparation, storage of DC vaccines, tumor-mediated immunosuppressive environment, identification of specific tumor antigens, and high degradation of antigen peptides in vivo limit the clinical application and affect the outcomes of these cancer vaccines. Recently, nanocarriers have been considered as a new approach for vaccine delivery. As biogenic nanocarriers, exosomes are small membrane vesicles secreted by cells that carry various proteins, RNAs, and lipids. More importantly, DC-derived exosomes (Dex) express tumor antigens, MHC molecules, and co-stimulatory molecules on their surface, which trigger the release of antigen-specific CD4+ and CD8+ T cells. With their membrane structure, Dex can avoid high degradation while ensuring favorable biocompatibility and biosafety in vivo. In addition, Dex can be stored in vitro for a longer period, which facilitates a significant reduction in production costs. Furthermore, they have shown better antitumor efficacy in preclinical studies compared with DC vaccines owing to their higher immunogenicity and stronger resistance to immunosuppressive effects. However, the clinical efficacy of Dex vaccines remains limited. In this review, we aimed to evaluate the efficacy of Dex as an anticancer nanovaccine.

Effect of Freeze-Thaw Cycles on Coal Pore Structure and Gas Emission Characteristics.

Here, we aim to clarify the influence of freeze-thaw cycle on pore structure and gas emission characteristics of coal body and to improve the application level of antipermeability and pumping technology based on freezing-induced cracking in a low-permeability coal seam. Freeze-thaw cycles of anthracite and coking coal were carried out in a freezer (-20 °C). Nuclear magnetic resonance was used to test the transformation characteristics of the freeze-thaw cycles on the pore structure of coal samples. The effect of freeze-thaw cycles on the gas emission characteristics of coal particles (1-3 mm) was studied using a self-built gas emission experimental platform (adsorption equilibrium gas pressure was 1.5 MPa). The results show that the pore structure of coal samples changes after the freeze-thaw cycle and the number of large pores and medium pores increases. The amount of gas emission, emission velocity, and gas diffusion coefficient of anthracite and coking coal all increase to different degrees after freeze-thaw cycles. The freeze-thaw damage of coking coal is greater than that of anthracite. In the third freeze-thaw cycle, the increase of each parameter is the largest, and the third freeze-thaw cycle is considered the optimal number of freezing-thawing cycles. The research results provide a theoretical basis for the production of low-permeability coal seam.

Respiratory symptoms as initial manifestations of interstitial lung disease in clinically amyopathic juvenile dermatomyositis: a case report with literature review.

BACKGROUND: Clinically amyopathic juvenile dermatomyositis (CAJDM) is a clinical subgroup of juvenile dermatomyositis (JDM), characterized by JDM rashes with little or no clinically evident muscle weakness. Interstitial lung disease (ILD) is an uncommon but potentially fatal complication of juvenile dermatomyositis (JDM). While adults with dermatomyositis-associated ILD usually present respiratory symptoms before or at the same time as skin muscle manifestations, only a few studies have covered the onset of respiratory symptoms of ILD in JDM patients, especially CAJDM. There is currently no clear effective treatment regime or any prognostic factors for CAJDM-associated ILD. CASE PRESENTATION: Here, we report the first case of a CAJDM patient who presented with respiratory symptoms as the initial manifestation. A 10-year-old male patient presented to the hospital with a complaint of progressive cough and chest pain. Violaceous macule and papules appeared a few days later and he was positive for anti-Ro-52 antibodies. Imaging showed diffuse interstitial infiltration in both lungs and lung function tests showed restrictive and obstructive ventilatory dysfunction. Muscular abnormalities were excluded by thigh magnetic resonance imaging (MRI) and electromyography. Skin biopsy showed pathognomonic findings consistent with DM. Lung biopsy indicated chronic inflammation of the mucosa. This patient was finally diagnosed with CAJDM complicated by ILD and prescribed methylprednisolone, immunoglobulin, prednisolone and mycophenolate mofetil (MMF) for treatment. The patient's cutaneous and respiratory manifestations were largely improved. We retrospectively reviewed this and another six cases with CAJDM-associated ILD reported previously to better understand its clinical characteristics and effective management. CONCLUSIONS: Initial respiratory symptoms with rapid progression in patients presenting Gottron papules should be considered manifestations of CAJDM-associated ILD. We also found a combination of corticosteroids, IVIG and MMF to be an effective method of arresting the progress of CAJDM-associated ILD and improving the prognosis of the patients.

Selective Catalysis Remedies Polysulfide Shuttling in Lithium-Sulfur Batteries.

The shuttling of soluble lithium polysulfides between the electrodes leads to serious capacity fading and excess use of electrolyte, which severely bottlenecks practical use of Li-S batteries. Here, selective catalysis is proposed as a fundamental remedy for the consecutive solid-liquid-solid sulfur redox reactions. The proof-of-concept Indium (In)-based catalyst targetedly decelerates the solid-liquid conversion, dissolution of elemental sulfur to polysulfides, while accelerates the liquid-solid conversion, deposition of polysulfides into insoluble Li2 S, which basically reduces accumulation of polysulfides in electrolyte, finally inhibiting the shuttle effect. The selective catalysis is revealed, experimentally and theoretically, by changes of activation energies and kinetic currents, modified reaction pathway together with the probed dynamically changing catalyst (LiInS2 catalyst), and gradual deactivation of the In-based catalyst. The In-based battery works steadily over 1000 cycles at 4.0 C and yields an initial areal capacity up to 9.4 mAh cm-2 with a sulfur loading of ≈9.0 mg cm-2 .

[Analysis of genomic copy number variants in a patient with congenital type Pelizaeus-Merzbacher disease].

OBJECTIVE: To explore the genotypic and phenotypic characteristics of a child with congenital Pelizaeus-Merzbacher disease. METHODS: Clinical, imaging and genetic characteristics of the child were retrospectively analyzed. RESULTS: The patient manifested significantly reduced muscle tension, apparent tremor of eyeballs, and retardation of motor development after birth. Cranial MRI at 6-month-old showed no myelinization of brain white matter, though no pathogenic variant was detected by clinical exome sequencing. A copy number variation was found at chrX: 102 192 246-103 045 526. The duplication has spanned approximately 853 kb and was recorded in the Decipher database to be associated with Pelizaeus-Merzbacher disease. Quantitative PCR confirmed that the duplication has derived from his mother. CONCLUSION: Reduced muscle tension, nystagmus, poor motor development, and absence of myelinization of white matter should alert the diagnosis of congenital type Pelizaeus-Merzbacher disease. Both sequence variant and copy number variation should be searched upon genetic testing. A clear diagnosis is required for genetic counseling.

Intestinal Surgery Contributes to Acute Cerebellar Ataxia Through Gut Brain Axis.

Introduction: Acute cerebellar ataxia (ACA) is the most common form of pediatric ataxia. Changes in gut flora can modulate the nervous system, influencing brain function via the gut-brain axis (GBA). This study aimed to illustrate the relationship between intestinal microbiota and ACA. Method: A total of 30 and 12 children were randomly sampled from history of intestinal surgery (HOIS) and no intestinal surgery groups (NHOIS), respectively. In addition, 10 healthy children who sought physical examination in Children's Hospital of Nanjing Medical University were recruited as a control group. The stool samples were 16S rRNA detected. Results: We observed that many ACA children had intestinal surgery history prior to the onset of ACA. The 16S rRNA sequencing indicated that HOIS and control groups were well-distinguished by principal component analysis. The discrepancy between HOIS and NHOIS groups were also displayed by principal component analysis score plot. However, no differences were found between NHOIS and control groups. The results of student's t-test were consistent with principal component analysis. A total of nine different genera were identified between HOIS and control groups. Five genera and a phylum showed significant differences between HOIS and NHOIS groups. Conclusion: Altered genera and phyla associated with ACA were identified. Our findings provide new insight into treating and preventing ACA.

Microstructure and Isothermal Oxidation of Ir-Rh Spark Plug Electrodes.

High-temperature oxidation tests were performed on pure iridium, rhodium, and the iridium alloys, IrRh10, IrRh25, and IrRh40, at 1100 °C in a stable air environment for 60 h. The results of the oxidation were analyzed by X-ray photoelectron spectroscopy (XPS). Microstructural changes of the Ir-Rh alloys were characterized by scanning electron microscopy (SEM). XPS analysis results show that the main oxide of the Ir-Rh alloy in a 1100 °C environment was Rh2O3, and SEM analysis shows that the surfaces of the Ir-Rh alloys after oxidation formed both linear and ellipse-shaped corrosion pits, and had the same direction with the wire-drawing process. The oxidation behavior of Ir-Rh alloys, including the mass change, the reason for the mass loss, and the role of Rh in improving oxidation resistance performance, are discussed.

Engineering of microscale vascularized fat that responds to perfusion with lipoactive hormones.

Current methods to treat large soft-tissue defects mainly rely on autologous transfer of adipocutaneous flaps, a method that is often limited by donor site availability. Engineered vascularized adipose tissues can potentially be a viable and readily accessible substitute to autologous flaps. In this study, we engineered a small-scale adipose tissue with pre-patterned vasculature that enables immediate perfusion. Vessels formed after one day of perfusion and displayed barrier function after three days of perfusion. Under constant perfusion, adipose tissues remained viable and responded to lipoactive hormones insulin and epinephrine with lipid accumulation and loss, respectively. Adipocyte growth correlated inversely with distance away from the feeding vessel, as predicted by a Krogh-type model.