Clinical study of 3D laparoscopic radical prostatectomy by transperitoneal and extraperitoneal approaches.

OBJECTIVE: Comparison of the clinical effectiveness and safety of three-dimensional transperitoneal laparoscopic radical prostatectomy (3D TLRP) versus 3D extraperitoneal LRP (3D ELRP) for prostate cancer. MATERIALS AND METHODS: To retrospectively analyze the clinical and regular postoperative follow-up data of patients who underwent 3D LRP performed by the same attending surgeon at the Affiliated Hospital of Bengbu Medical College between 2017 and 2022. A total of 82 patients who met the criteria were included. They were divided into 3D TLRP (n = 39) and 3D ELRP groups (n = 43) according to the surgical approach. The preoperative, intraoperative, and postoperative data were compared. RESULTS: There were no statistically significant differences in preoperative characteristics between the two groups. There were also no statistically significant differences between the 3D TLRP and 3D ELRP groups in terms of intraoperative blood transfusion rate (12.82% vs. 2.33%), positive lymph node rate (11.11% vs. 2.38%), positive surgical margin rate (12.82% vs. 6.98%), pathological Gleason score, postoperative clinical stage, perioperative complication rate (10.26% vs. 4.65%), immediate urinary control rate (56.41% vs. 58.14%), 3-month postoperative urinary control rate (76.92% vs. 74.42%), 6-month postoperative urinary control rate (87.18% vs. 83.72%), 6-month postoperative biochemical recurrence rate (7.69% vs. 9.30%), or 6-month postoperative sexual function recovery rate (2.56% vs. 2.33%) (P > 0.05). Compared with the 3D ELRP group, the 3D TLRP group had a longer operative time (232.36 ± 48.52 min vs. 212.07 ± 41.76 min), more estimated blood loss (150.000 [100.0, 200.0] vs. 100.000 [100.0, 125.0]), longer recovery of gastrointestinal function (2.72 ± 0.89 vs. 2.26 ± 0.88), longer duration of drainage tube retention (5.69 ± 1.79 vs. 4.28 ± 2.68), and longer hospitalization time (12.54 ± 4.07 vs. 10.88 ± 2.97), with statistical significance (P < 0.05). CONCLUSION: 3D TLRP and 3D ELRP have similar oncologic and functional outcomes. Clinically, physicians can choose a reasonable procedure according to the patient's specific situation and their own surgical experience.

Investigation of 3D Printed Bioresorbable Vascular Scaffold Crimping Behavior.

The rise in additive manufacturing (AM) offers myriad opportunities for 3D-printed polymeric vascular scaffolds, such as customization and on-the-spot manufacturing, in vivo biodegradation, incorporation of drugs to prevent restenosis, and visibility under X-ray. To maximize these benefits, informed scaffold design is critical. Polymeric bioresorbable vascular scaffolds (BVS) must undergo significant deformation prior to implantation in a diameter-reduction process known as crimping which enables minimally invasive surgery. Understanding the behavior of vascular scaffolds in this step provides twofold benefits: first, it ensures the BVS is able to accommodate stresses occurring during this process to prevent failure, and further, it provides information on the radial strength of the BVS, a key metric to understanding its post-implant performance in the artery. To capitalize on the fast manufacturing speed AM provides, a low time cost solution for understanding scaffold performance during this step is necessary. Through simulation of the BVS crimping process in ABAQUS using experimentally obtained bulk material properties, we have developed a qualitative analysis tool which is capable of accurately comparing relative performance trends of varying BVS designs during crimping in a fraction of the time of experimental testing, thereby assisting in the integration of informed design into the additive manufacturing process.

A polydiolcitrate-MoS2 composite for 3D printing Radio-opaque, Bioresorbable Vascular Scaffolds.

Implantable polymeric biodegradable devices, such as biodegradable vascular stents or scaffolds, cannot be fully visualized using standard X-ray-based techniques, compromising their performance due to malposition after deployment. To address this challenge, we describe composites of methacrylated poly(1,12 dodecamethylene citrate) (mPDC) and MoS2 nanosheets to fabricate novel X-ray visible radiopaque and photocurable liquid polymer-ceramic composite (mPDC-MoS2). The composite was used as an ink with micro continuous liquid interface production (µCLIP) to fabricate bioresorbable vascular scaffolds (BVS). Prints exhibited excellent crimping and expansion mechanics without strut failures and, importantly, required X-ray visibility in air and muscle tissue. Notably, MoS2 nanosheets displayed physical degradation over time in a PBS environment, indicating the potential for producing bioresorbable devices. mPDC-MoS2 is a promising bioresorbable X-ray-visible composite material suitable for 3D printing medical devices, particularly vascular scaffolds or stents, that require non-invasive X-ray-based monitoring techniques for implantation and evaluation. This innovative composite system holds significant promise for the development of biocompatible and highly visible medical implants, potentially enhancing patient outcomes and reducing medical complications.

An Integrally Formed Janus Hydrogel for Robust Wet-Tissue Adhesive and Anti-Postoperative Adhesion.

Facile fabrication of asymmetrically adhesive hydrogel with robust wet tissue adhesion simultaneously with effective anti-postoperative adhesion still remains a great challenge. In this work, an integrally formed Janus hydrogel is facilely fabricated in one step by controlling the interfacial distribution of free carboxyl groups on the two sides of hydrogels. At a lower stirring speed, the generated bigger sized emulsion droplets mainly occupy the top surface of hydrogel, which effectively hinders the exposition of carboxyl groups on the top surface, driving them to be more distributed on the bottom surface, ultimately resulting in the poor adhesion of top surface but robust adhesion of bottom surface to various wet tissue even underwater. The difference in adhesive strength achieves as high as 20 times between the two surfaces. In vivo rabbit experiment outcomes clearly validate that the bottom surface of hydrogel firmly adheres to the stomach defect, and the other opposite surface can efficiently address the postoperative adhesion problem. Besides, this hydrogel exhibits superior mechanical toughness and conductivity which has been used as a highly adhesive strain sensor to real-time monitor the beating heart in vivo. This simple yet effective strategy provides a much more feasible approach for creating Janus hydrogels bioadhesives.

Polyvinyl chloride-based dielectric elastomer with high permittivity and low viscoelasticity for actuation and sensing.

Dielectric elastomers (DEs) are widely used in soft actuation and sensing. Current DE actuators require high driving electrical fields because of their low permittivity. Most of DE actuators and sensors suffer from high viscoelastic effects, leading to high mechanical loss and large shifts of signals. This study demonstrates a valuable strategy to produce polyvinyl chloride (PVC)-based elastomers with high permittivity and low viscoelasticity. The introduction of cyanoethyl cellulose (CEC) into plasticized PVC gel (PVCg) not only confers a high dielectric permittivity (18.9@1 kHz) but also significantly mitigates their viscoelastic effects with a low mechanical loss (0.04@1 Hz). The CEC/PVCg actuators demonstrate higher actuation performances over the existing DE actuators under low electrical fields and show marginal displacement shifts (7.78%) compared to VHB 4910 (136.09%). The CEC/PVCg sensors display high sensitivity, fast response, and limited signal drifts, enabling their faithful monitoring of multiple human motions.

3D laparoscopic resection of renal venous aneurysms: a rare case report.

OBJECTIVE: Visceral venous aneurysms are very rare, especially in the kidney. The diagnosis of renal venous aneurysms is difficult. If complications such as thrombosis, embolism or rupture, there can be corresponding clinical symptoms. In severe cases, it can lead to the death of the patient. Endoscopic resection of renal venous aneurysms has not been reported in the literature. This paper preliminarily discusses the experience of laparoscopic resection of renal venous aneurysms. METHODS: Recently, a patient with left retroperitoneal space occupying lesion was admitted to our hospital. More than a year ago, the patient was found to have left retroperitoneal space occupying lesion by CT plain scan, accompanied by occasional upper abdominal and precordial discomfort at night. After admission, enhanced CT showed that the size of the space occupying lesion was about 3.0×2.0×2.0 cm, adjacent to the left abdominal aorta, left renal artery and left renal vein. The space occupying density was similar to that of renal parenchyma in the unenhanced phase, whereas the enhancement was less pronounced in the arterial phase, more pronounced in the venous phase, and the attenuation was less pronounced in the delayed phase. After further refining the preoperative preparation, the surgical approach was "transabdominal 3D laparoscopic left retroperitoneal space occupying resection". Intraoperatively, a space occupying was found at the angle between the abdominal aorta and renal pedicle vessels, which were dark red, soft in quality and had a heavy adhesion to the renal artery. An atraumatic vascular clip was used to block the left renal artery, the gap between the free renal artery and the space occupying, and then the renal artery noninvasive vascular clip was loosened. Continuing free space occupying, we found that the space occupying originated from the left renal vein, gradually enlarged, terminated at the psoas muscle, and connected with the renal vein approximately 1 cm in width. Closely apposed renal veins were blocked with a vascular clip, clipped, and finally a complete resection space was taken. RESULTS: The procedure was uneventful, without trauma to the surrounding tissue organs. After complete resection of retroperitoneal mass, the patient recovered well. No complications were found, and the discomfort symptoms disappeared. The pathological result was renal venous aneurysm, which was considered due to lumbar venous variation. CONCLUSION: No treatment modality for the endoscopic resection of renal venous aneurysms has been documented, and the previous treatment modalities were usually nephrectomy or intervention. This surgical procedure may be the first in the world and open a new way for the diagnosis and treatment of renal venous aneurysms.

Source, Distribution, and Risk Estimation of Hazardous Elements in Farmland Soils in a Typical Alluvial-Lacustrine Transition Basin, Hunan Province.

Increased concentrations of heavy metals in soil due to anthropogenic activities pose a considerable threat to human health and require constant attention. This study investigates the spatial distribution of heavy metals (Cd, Pb, Zn, Sb) and metalloids (As) in a typical alluvial-lacustrine transition basin and calculates the bioavailable forms of elements posing a direct threat. Qualitative and quantitative methods were used to identify the sources of contaminants, after which an ecological risk assessment was conducted. Total (T) As, Pb, and Zn decreased with the depth, whereas Cd and Sb increased in surface (0-20 cm) soil. Bioavailable (Bio) Cd and Pb in the topsoil were regulated by pH and organic matter, whereas Bio-Zn was regulated by soil pH. Within deeper soil layers, the combined effects of pH, organic matter, and clay contents regulated the bio-elements. The results of multiple methods and local investigation showed that TSb (65.3%) was mainly derived from mining activities, TCd (53.2%) and TZn (53.7%) were derived from direct pollution by industrial production and agricultural fertilizers, respectively, and TA (55.6%) was mainly derived from the soil parent material. TPb was related to vehicle exhaust emissions and atmospheric deposition from industrial activities. Although the potential ecological risk in the study area remains relatively low, there is a need for continuous monitoring of the potential ecological risks of Cd and Sb. This study can act as a reference for the prevention and mitigation of heavy metal contamination of alluvial-lacustrine transition basins.

3D-Printed Radiopaque Bioresorbable Stents to Improve Device Visualization.

Bioresorbable stents (BRS) hold great promise for the treatment of many life-threatening luminal diseases. Tracking and monitoring of stents in vivo is critical for avoiding their malposition and inadequate expansion, which often leads to complications and stent failure. However, obtaining high X-ray visibility of polymeric BRS has been challenging because of their intrinsic radiolucency. This study demonstrates the use of photopolymerization-based 3D printing technique to fabricate radiopaque BRS by incorporating iodixanol, a clinical contrast agent, into a bioresorbable citrate-based polymer ink. The successful volumetric dispersion of the iodixanol through the 3D-printing process confers strong X-ray visibility of the produced BRS. Following in vitro degradation, the 3D-printed BRS embedded in chicken muscle maintains high X-ray visibility for at least 4 weeks. Importantly, the 3D-printed radiopaque BRS demonstrates good cytocompatibility and strong mechanical competence in crimping and expansion, which is essential for minimally invasive stent deployment. In addition, it is found that higher loading concentrations of iodixanol, e.g. 10 wt.%, results in more strut fractures in stent crimping and expansion. To conclude, this study introduces a facile strategy to fabricate radiopaque BRS through the incorporation of iodixanol in the 3D printing process, which could potentially increase the clinical success of BRS.

Vascular Grafts with Tailored Stiffness and a Ligand Environment via Multiarmed Polymer Sheath for Expeditious Regeneration.

The bypass graft is the mainstream of surgical intervention to treat vascular diseases. Ideal bypass materials, yet to be developed, require mechanical properties, availability, clinically feasible manufacturing logistics, and bioactivities with precise physicochemical cues defined to guide cell activities for arterial regeneration. Such needs instigated our fabrication of vascular grafts, which consist of coaxial, nanostructured fibers exhibiting a polycaprolactone (PCL) core and a photoclickable, 4-arm thiolated polyethylene glycol-norbornene (PEG-NB) sheath. The graft strength and bioactivity were modulated by the PCL concentration and the peptides (RGD, transforming growth factor ß-1 or TGF-ß1) conjugated to thiol-ene of PEG-NB, respectively. Structural, physical, and mechanical characterizations demonstrated that the fibrous grafts mimicked the key features of the native extracellular matrix, including a crosslinked fiber network for structural stability, viscoelasticity emulating arteries, hydration property, and high porosity for cell infiltration. Meanwhile, these grafts displayed strength and toughness exceeding or meeting surgical criteria. Furthermore, the grafts with higher PCL concentration (3 vs 1.8%) showed thicker fibers, lower porosity and pore size, and increased elastic and storage moduli. Graft bioactivity was determined by the mesenchymal stem cell (MSC) behaviors on the grafts and arterial regeneration in vivo using interposition grafting. Results showed that the cell adhesion and proliferation increased with the RGD density (25 vs 5 mM). After 1 week implantation, all peptide-functionalized PCL/PEG-NB grafts with or without MSC preseeding, as opposed to PCL grafts, showed expeditious endothelial lining, abundant vascular cell infiltration, and matrix production. Compared to RGD grafts, RGD/TGF-ß1 grafts enhanced MSC differentiation into smooth muscle cells in vitro and developed thicker smooth muscle cell layers in vivo. Overall, the versatile porous vascular grafts offer superior properties and tunability for future translation.

On-Chip Acousto Thermal Shift Assay for Rapid and Sensitive Assessment of Protein Thermodynamic Stability.

Thermal shift assays (TSAs) have been extensively used to study thermodynamics of proteins and provide an efficient means to assess protein-ligand binding or protein-protein interactions. However, existing TSAs have limitations, such as being time consuming, labor intensive, or having low sensitivity. Herein, an acousto thermal shift assay (ATSA), the first ultrasound enabled TSA, is reported for real-time analysis of protein thermodynamic stability. It capitalizes the coupling of unique acoustic mechanisms to achieve protein unfolding, concentration, and measurement on a single microfluidic chip within minutes. Compared to conventional TSA methods, the ATSA technique enables ultrafast (at least 30 times faster), highly sensitive (7-34 folds higher), and label-free monitoring of protein-ligand interactions and protein stability. ATSA paves new avenues for protein analysis in biology, medicine, and fast diagnosis.

Tethering transforming growth factor ß1 to soft hydrogels guides vascular smooth muscle commitment from human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) hold great promise for vascular smooth muscle regeneration. However, most studies have mainly relied on extended supplementation of sophisticated biochemical regimen to drive MSC differentiation towards vascular smooth muscle cells (vSMCs). Herein we demonstrate a concomitant method that exploits the advantages of biomimetic matrix stiffness and tethered transforming growth factor ß1 (TGF-ß1) to guide vSMC commitment from human MSCs. Our designed poly(ethylene glycol) hydrogels, presenting a biomimetic stiffness and tethered TGF-ß1, provide an instructive environment to potently upregulate smooth muscle marker expression in vitro and in vivo. Importantly, it significantly enhances the functional contractility of vSMCs derived from MSCs within 3 days. Interestingly, compared to non-tethered one, tethered TGF-ß1 enhanced the potency of vSMC commitment on hydrogels. We provide compelling evidence that combining stiffness and tethered TGF-ß1 on poly(ethylene glycol) hydrogels can be a promising approach to drastically enhance maturation and function of vSMCs from stem cell differentiation in vitro and in vivo. STATEMENT OF SIGNIFICANCE: A fast, reliable and safe regeneration of vascular smooth muscle cells (vSMCs) from stem cell differentiation is promising for vascular tissue engineering and regenerative medicine applications, but remains challenging. Herein, a photo-click hydrogel platform is devised to recapitulate the stiffness of vascular tissue and appropriate presentation of transforming growth factor ß1 (TGF-ß1) to guide vSMC commitment from mesenchymal stem cells (MSCs). We demonstrate that such concomitant method drastically enhanced regeneration of mature, functional vSMCs from MSCs in vitro and in vivo within only a 3-days span. This work is not only of fundamental scientific importance, revealing how physiochemical factors and the manner of their presentation direct stem cell differentiation, but also attacks the long-standing difficulty in regenerating highly functional vSMCs within a short period.

Micro/nano-structured TiO2 surface with dual-functional antibacterial effects for biomedical applications.

Implant-associated infections are generally difficult to cure owing to the bacterial antibiotic resistance which is attributed to the widespread usage of antibiotics. Given the global threat and increasing influence of antibiotic resistance, there is an urgent demand to explore novel antibacterial strategies other than using antibiotics. Recently, using a certain surface topography to provide a more persistent antibacterial solution attracts more and more attention. However, the clinical application of biomimetic nano-pillar array is not satisfactory, mainly because its antibacterial ability against Gram-positive strain is not good enough. Thus, the pillar array should be equipped with other antibacterial agents to fulfill the bacteriostatic and bactericidal requirements of clinical application. Here, we designed a novel model substrate which was a combination of periodic micro/nano-pillar array and TiO2 for basically understanding the topographical bacteriostatic effects of periodic micro/nano-pillar array and the photocatalytic bactericidal activity of TiO2. Such innovation may potentially exert the synergistic effects by integrating the persistent topographical antibacterial activity and the non-invasive X-ray induced photocatalytic antibacterial property of TiO2 to combat against antibiotic-resistant implant-associated infections. First, to separately verify the topographical antibacterial activity of TiO2 periodic micro/nano-pillar array, we systematically investigated its effects on bacterial adhesion, growth, proliferation, and viability in the dark without involving the photocatalysis of TiO2. The pillar array with sub-micron motif size can significantly inhibit the adhesion, growth, and proliferation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Such antibacterial ability is mainly attributed to a spatial confinement size-effect and limited contact area availability generated by the special topography of pillar array. Moreover, the pillar array is not lethal to S. aureus and E. coli in 24 h. Then, the X-ray induced photocatalytic antibacterial property of TiO2 periodic micro/nano-pillar array in vitro and in vivo will be systematically studied in a future work. This study could shed light on the direction of surface topography design for future medical implants to combat against antibiotic-resistant implant-associated infections without using antibiotics.

Pharmacokinetics of ceftiofur sodium in cats following a single intravenous and subcutaneous injection.

Ceftiofur, a third-generation cephalosporin antibiotic, is being extensively used by pet doctors in China. In the current study, the detection method was developed for ceftiofur and its metabolites, desfuroylceftiofur (DCE) and desfuroylceftiofur conjugates (DCEC), in feline plasma. Then, the pharmacokinetics studies were performed following one single intravenous and subcutaneous injection of ceftiofur sodium in cats both at 5 mg/kg body weight (BW) (calculated as pure ceftiofur). Ceftiofur, DCE, and DCEC were extracted from plasma samples, then derivatized and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetics parameters. The terminal half-life (t1/2λz ) was calculated as 11.29 ± 1.09 and 10.69 ± 1.31 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (VSS ) were determined as 14.14 ± 1.09 ml hr-1  kg-1 and 241.71 ± 22.40 ml/kg, respectively. After subcutaneous injection, the peak concentration (Cmax ; 14.99 ± 2.29 µg/ml) was observed at 4.17 ± 0.41 hr, and the absorption half-life (t1/2ka ) and absolute bioavailability (F) were calculated as 2.83 ± 0.46 hr and 82.95%±9.59%, respectively. The pharmacokinetic profiles of ceftiofur sodium and its related metabolites demonstrated their relatively slow, however, good absorption after subcutaneous administration, poor distribution, and slow elimination in cats. Based on the time of drug concentration above the minimum inhibitory concentration (MIC) (T>MIC) calculated in the current study, an intravenous or subcutaneous dose at 5 mg/kg BW of ceftiofur sodium once daily is predicted to be effective for treating feline bacteria with a MIC value of ≤4.0 µg/ml.

Coaxial PCL/PEG-thiol-ene microfiber with tunable physico-chemical properties for regenerative scaffolds.

Tissue regeneration requires scaffolds that exhibit mechanical properties similar to the tissues to be replaced while allowing cell infiltration and extracellular matrix production. Ideally, the scaffolds' porous architecture and physico-chemical properties can be precisely defined to address regenerative needs. We thus developed techniques to produce hybrid fibers coaxially structured with a polycaprolactone core and a 4-arm, polyethylene glycol thiol-norbornene sheath. We assessed the respective effects of crosslink density and sheath polymer size on the scaffold architecture, physical and mechanical properties, as well as cell-scaffold interactions in vitro and in vivo. All scaffolds displayed high elasticity, swelling and strength, mimicking soft tissue properties. Importantly, the thiol-ene hydrogel sheath enabled tunable softness and peptide tethering for cellular activities. With increased photopolymerization, stiffening and reduced swelling of scaffolds were found due to intra- and inter-fiber crosslinking. More polymerized scaffolds also enhanced the cell-scaffold interaction in vitro and induced spontaneous, deep cell infiltration to produce collagen and elastin for tissue regeneration in vivo. The molecular weight of sheath polymer provides an additional mechanism to alter the physical properties and biological activities of scaffolds. Overall, these robust scaffolds with tunable elasticity and regenerative cues offered a versatile and effective platform for tissue regeneration.

Coaxially-structured fibres with tailored material properties for vascular graft implant.

Readily-available small-diameter arterial grafts require a great combination of materials properties, including high strength, compliance, suturability, blood sealing and anti-thrombogenicity, as well as anti-kinking property for those used in challenging anatomical situations. We have constructed grafts composed of coaxially-structured polycaprolactone (PCL)/gelatin nanofibres, and tailored the material structures to achieve high strength, compliance and kink resistance, as well as excellent water sealing and anti-thrombogenicity. Coaxially-structured fibres in the grafts provided mechanical stability through the core, while flexibility and cell adhesion through the sheath. Results showed that graft compliance increased while strength decreased with the concentration ratio between core and sheath polymers. Compared to pure PCL fibrous surfaces, coaxial PCL/gelatin fibrous surfaces potently inhibited platelet adhesion and activation, providing excellent anti-thrombogenicity. To render sufficient burst strength and suturability, an additional layer of pure PCL was necessary to cap the layer of coaxial PCL/gelatin fibres. The two-layered grafts with the wall thickness comparable to native arteries demonstrated artery-like compliance and kink resistance, properties important to arteries under complex mechanical loading. The in vivo evaluation was performed using the interposition carotid artery graft model in rabbits for three months. Interestingly, results from ultrasonic imaging and histological analysis demonstrated that the two-layered grafts with a thinner outer PCL layer, which possessed higher compliance and kink resistance, showed increased blood flow, minimal lumen reduction and fibrosis. All vascular grafts exhibited patency and induced limited cell infiltration. Together, we presented a facile and useful approach to fabricate vascular grafts with superior graft performances, biomechanical properties, and blood compatibility. Grafts with artery-like compliance and flexibility have demonstrated improved implantation outcomes.

Hydrophilic Poly(vinylidene Fluoride) Film with Enhanced Inner Channels for Both Water- and Ionic Liquid-Driven Ion-Exchange Polymer Metal Composite Actuators.

This study presents a novel and facile strategy to fabricate a hydrophilic poly(vinylidene fluoride) (PVDF) electrolyte film with enhanced inner channels for a high-performance and cost-effective ion-exchange polymer metal composite (IPMC) actuator. The resultant PVDF composite film is composed of hierarchical micro/nanoscale structures: well-defined polymer grains with a diameter of ∼20 µm and much finer particles with a diameter of ∼390 nm, producing three-dimensional interconnected, hierarchical inner channels to facilitate ion migration of IPMC. Interestingly, the electrolyte matrix film has a high porosity of 15.8% and yields a high water uptake of 44.2% and an ionic liquid (IL, [EMIm]·[BF4]) uptake of 38.1% to make both water-driven and IL-driven IPMC actuators because of the introduction of polar polyvinyl pyrrolidone. Compared to the conventional PVDF/IL-based IPMC, both water-driven and IL-driven PVDF-based IPMCs exhibit high ion migration rates, thus effectively improving the actuation frequency and producing remarkably higher levels of actuation force and displacement. Specifically, the force outputs are increased by 13.4 and 3.0 folds, and the displacement outputs are increased by 2.2 and 1.9 folds. Using an identical electrolyte matrix, water-driven IPMC exhibits stronger electromechanical performance, benefiting to make IPMC actuator with high levels of force and power outputs, whereas IL-driven IPMC exhibits a more stable electromechanical performance, benefiting to make long lifetime IPMC actuator in air. Thus, the resultant IPMCs are promising in the design of artificial muscles with tunable electromechanical performance for flexible actuators or displacement/vibration sensors at low cost.

Cancer-associated fibroblast-derived exosomal microRNA-98-5p promotes cisplatin resistance in ovarian cancer by targeting CDKN1A.

BACKGROUND: Ovarian cancer (OC) is a gynecological malignancy with a high mortality. Cisplatin-based treatment is the typical treatment regimen for OC patients; however, it may cause unfavorable resistance. The current study intends to explore the function of cancer-associated fibroblast (CAF)-derived exosomal microRNA-98-5p (miR-98-5p) in cisplatin resistance in OC, and the participation of CDKN1A. METHODS: Bioinformatics analysis was employed in order to obtain cisplatin resistance-related differential genes in OC as well as possible upstream regulatory miRs. After gain- and loss-of-function assays in OC cells, RT-qPCR and western blot analysis were employed to measure CDKN1A and miR-98-5p expression. Dual luciferase reporter assay was applied to verify the targeting relationship between miR-98-5p and CDKN1A. CAFs were treated with miR-98-5p inhibitor, and then exosomes were isolated and co-cultured with OC cells. CCK-8, colony formation and flow cytometry assays were conducted to assess cell proliferation, cell colony formation, cell cycle distribution and cell apoptosis, respectively. At last, xenograft tumor in nude mice was carried out to test whether exosomal miR-98-5p could affect cisplatin resistance in OC in vivo. RESULTS: CDKN1A was highly expressed in cisplatin-sensitive OC cell lines, and silencing CDKN1A significantly promoted proliferation and cell cycle entry but decreased apoptosis in cisplatin-sensitive OC cells. miR-98-5p targeted CDKN1A to inhibit CDKN1A expression. CAF-derived exosomal miR-98-5p increased OC cell proliferation and cell cycle entry, but suppressed cell apoptosis. Furthermore, exosomal miR-98-5p promoted cisplatin resistance and downregulated CDKN1A in nude mice. CONCLUSION: Collectively, CAF-derived exosomes carrying overexpressed miR-98-5p promote cisplatin resistance in OC by downregulating CDKN1A.

Orthogonal programming of heterogeneous micro-mechano-environments and geometries in three-dimensional bio-stereolithography.

Engineering heterogeneous micro-mechano-microenvironments of extracellular matrix is of great interest in tissue engineering, but spatial control over mechanical heterogeneity in three dimensions is still challenging given the fact that geometry and stiffness are inherently intertwined in fabrication. Here, we develop a layer-by-layer three-dimensional (3D) printing paradigm which achieves orthogonal control of stiffness and geometry by capitalizing on the conventionally adverse effect of oxygen inhibition on free-radical polymerization. Controlled oxygen permeation and inhibition result in photo-cured hydrogel layers with thicknesses only weakly dependent to the ultraviolet exposure dosage. The dosage is instead leveraged to program the crosslink density and stiffness of the cured structures. The programmable stiffness spans nearly an order of magnitude (E ~ 2-15 kPa) within the physiologically relevant range. We further demonstrate that extracellular matrices with programmed micro-mechano-environments can dictate 3D cellular organization, enabling in vitro tissue reconstruction.

Biomimetic soft fibrous hydrogels for contractile and pharmacologically responsive smooth muscle.

The ability to assess changes in smooth muscle contractility and pharmacological responsiveness in normal or pathological-relevant vascular tissue environments is critical to enable vascular drug discovery. However, major challenges remain in both capturing the complexity of in vivo vascular remodeling and evaluating cell contractility in complex, tissue-like environments. Herein, we developed a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition to resemble the native vascular tissue environment. This hydrogel platform was further combined with the combinatory protein array technology as well as advanced approaches to measure cell mechanics and contractility, thus permitting evaluation of smooth muscle functions in a variety of tissue-like microenvironments. Our results demonstrated that biomimetic fibrous structure played a dominant role in smooth muscle function, while the presentation of adhesion proteins co-regulated it to various degrees. Specifically, fibre networks enabled cell infiltration and upregulated expression of actomyosin proteins in contrast to flat hydrogels. Remarkably, fibrous structure and physiologically relevant stiffness of hydrogels cooperatively enhanced smooth muscle contractility and pharmacological responses to vasoactive drugs at both the single cell and intact tissue levels. Together, this study is the first to demonstrate alterations of human vascular smooth muscle contractility and pharmacological responsiveness in biomimetic soft, fibrous environments with a cellular array platform. The integrated platform produced here could enable investigations for pathobiology and pharmacological interventions by developing a broad range of patho-physiologically relevant in vitro tissue models. STATEMENT OF SIGNIFICANCE: Engineering functional smooth muscle in vitro holds the great potential for diseased tissue replacement and drug testing. A central challenge is recapitulating the smooth muscle contractility and pharmacological responses given its significant phenotypic plasticity in response to changes in environment. We present a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition that enables the creation of functional smooth muscle tissues in the native-like vascular tissue microenvironment. Such fibrous hydrogel is further combined with the combinatory protein array technology to construct a cellular array for evaluation of smooth muscle phenotype, contraction, and cell mechanics. The integrated platform produced here could be promising for developing a broad range of normal or diseased in vitro tissue models.

A photoclickable peptide microarray platform for facile and rapid screening of 3-D tissue microenvironments.

Microarrays are powerful experimental tools for high-throughput screening of cellular behavior in multivariate microenvironments. Here, we present a new, facile and rapid screening method for probing cellular behavior in 3D tissue microenvironments. This method utilizes a photoclickable peptide microarray platform developed using electrospun fibrous poly(ethylene glycol) hydrogels and microarray contact printing. We investigated the utility of this platform with five different peptide motifs and ten cell types including stem, terminally differentiated, cancer or immune cells that were from either primary origin or cell lines and from different species. We validated the capabilities of this platform to screen arrays consisting of multiple peptide motifs and concentrations for selectivity to cellular adhesion and morphology. Moreover, this platform is amenable to controlled spatial presentation of peptides. We show that by leveraging the differential attachment affinities for two cell types to two different peptides, this platform can also be used to investigate cell-cell interactions through miniature co-culture peptide arrays. Our fibrous peptide microarray platform enables high-throughput screening of 3D tissue microenvironments in a facile and rapid manner to investigate cell-matrix interactions and cell-cell signaling and to identify optimal tissue microenvironments for cell-based therapies.