The Role of TGF-ß during Pregnancy and Pregnancy Complications.

Transforming growth factor beta (TGF-ß), a multifunctional cytokine, is one of the most important inflammatory cytokines closely related to pregnancy. It plays significant roles in hormone secretion, placental development, and embryonic growth during pregnancy. TGF-ß is implicated in embryo implantation and inhibits the invasion of extraepithelial trophoblast cells. It also moderates the mother-fetus interaction by adjusting the secretion pattern of immunomodulatory factors in the placenta, consequently influencing the mother's immune cells. The TGF-ß family regulates the development of the nervous, respiratory, and cardiovascular systems by regulating gene expression. Furthermore, TGF-ß has been associated with various pregnancy complications. An increase in TGF-ß levels can induce the occurrences of pre-eclampsia and gestational diabetes mellitus, while a decrease can lead to recurrent miscarriage due to the interference of the immune tolerance environment. This review focuses on the role of TGF-ß in embryo implantation and development, providing new insights for the clinical prevention and treatment of pregnancy complications.

Formation of Size-Controllable Tetragonal Nanoprisms by Crystallization-Directed Ionic Self-Assembly of Anionic Porphyrin and PEO-Containing Triblock Cationic Copolymer.

The creation of anisotropic nanostructures with precise size control is desirable for new properties and functions, but it is challenging for ionic self-assembly (ISA) because of the non-directional electrostatic interactions. Herein, the formation of size-controllable tetragonal nanoprisms is reported via crystallization-directed ionic self-assembly (CDISA) through evaporating a micellar solution on solid substrates. First, ISA is designed with a crystalline polyethylene oxide (PEO) containing cationic polymer poly(2-(2-guanidinoethoxy)ethyl methacrylate)-b-poly(ethyleneoxide)-b-poly(2-(2-guanidinoethoxy)-ethylmethacrylate) (PGn -PEO230 -PGn ) and an anionic 5,10,15,20-Tetrakis(4-sulfonatophenyl) porphyrin (TPPS) to form micelles in aqueous solution. The PG segments binds excessive TPPS with amplenet chargeto form hydrophilic corona, while the PEO segments are unprecedentedly dehydrated and tightly packed into cores. Upon naturally drying the micellar solution on a silicon wafer, PEO crystallizationdirects the micelles to aggregate into square nanoplates, which are further connected to nanoprisms. Length and width of the nanoprisms can be facilely tuned by varying the initial concentration. In this hierarchical process, the aqueous self-assembly is prerequisite and the water evaporation rate is crucial for the formation of nanostructures, which provides multiple factors for morphology regulating. Such precise size-control strategy is highly expected to provide a new vision for the design of advanced materials with size controllable anisotropic nanostructures.

Trio-pharmacophore DNA-encoded chemical library for simultaneous selection of fragments and linkers.

The split-and-pool method has been widely used to synthesize chemical libraries of a large size for early drug discovery, albeit without the possibility of meaningful quality control. In contrast, a self-assembled DNA-encoded chemical library (DEL) allows us to construct an m x n-member library by mixing an m-member and an n-member pre-purified sub-library. Herein, we report a trio-pharmacophore DEL (T-DEL) of m x l x n members through assembling three pre-purified and validated sub-libraries. The middle sub-library is synthesized using DNA-templated synthesis with different reaction mechanisms and designed as a linkage connecting the fragments displayed on the flanking two sub-libraries. Despite assembling three fragments, the resulting compounds do not exceed the up-to-date standard of molecular weight regarding drug-likeness. We demonstrate the utility of T-DEL in linker optimization for known binding fragments against trypsin and carbonic anhydrase II and by de novo selections against matrix metalloprotease-2 and -9.

Combining high throughput array synthesis and growth algorithm to discover TNF-α binders with new structures and properties.

Identifying new chemical structures against protein targets of interest represents one of the major challenges in drug discovery. As the major experimental method, high throughput screenings are performed with existing chemical libraries, thus restricting its capability to explore high molecular diversity. Herein, we report the use of high throughput array synthesis technology, in combination with growth algorithm, to discover binders for proinflammatory cytokine TNF-α. After 6 iterations of Library design - Array synthesis - Screening (i-LAS), one identified compound T17 has shown a kd value of 14.8 µM, and can rescue L929 cells from TNF-α mediated cytotoxicity. Further engineering T17 in various forms of oligomers have led to low nM binders. More interestingly, through tuning the multi-valent interaction with TNF-α, the high affinity oligomers can be switched from inhibitors to activators, leading to the hypothesis of an oligomerization-induced receptor activation mechanism. The i-LAS technology has allowed us to discover new binder structures, which can be further engineered into molecules with novel properties.

Surface Hydrophobization Provides Hygroscopic Supramolecular Plastics Based on Polysaccharides with Damage-Specific Healability and Room-Temperature Recyclability.

Supramolecular materials with room-temperature healability and recyclability are highly desired because they can extend materials lifetimes and reduce resources consumption. Most approaches toward healing and recycling rely on the dynamically reversible supramolecular interactions, such as hydrogen, ionic and coordinate bonds, which are hygroscopic and vulnerable to water. The general water-induced plasticization facilitates the healing and reprocessing process but cause a troubling problem of random self-adhesion. To address this issue, here it is reported that by modifying the hygroscopic surfaces with hydrophobic alkyl chains of dodecyltrimethoxysilane (DTMS), supramolecular plastic films based on commercial raw materials of sodium alginate (SA) and cetyltrimethylammonium bromide (CTAB) display extraordinary damage-specific healability. Owing to the hydrophobic surfaces, random self-adhesion is eliminated even under humid environment. When damage occurs, the fresh surfaces with ionic groups and hydroxyl groups expose exclusively at the damaged site. Thus, damage-specific healing can be readily facilitated by water-induced plasticization. Moreover, the films display excellent room-temperature recyclability. After multiple times of reprocessing and re-modifying with DTMS, the rejuvenated films exhibit fatigueless mechanical properties. It is anticipated that this approach to damage-specific healing and room-temperature recycling based on surface hydrophobization can be applied to design various of supramolecular plastic polysaccharides materials for building sustainable societies.

The timing of intravenous oxytocin administration is crucial to minimize perioperative blood loss during first-trimester suction curettage for missed abortion.

BACKGROUND: Oxytocin is commonly used to reduce blood loss during suction curettage for missed abortion. However, the potential of oxytocin to mitigate blood loss in early pregnancy remains controversial. Based on the hypothesis that the "timing" of oxytocin administration may be a critical factor, we investigated whether the timing of intravenous (IV) administration is associated with reduced perioperative blood loss during first-trimester suction curettage for missed abortion. METHODS: The medical charts of 146 patients with ultrasound-confirmed first-trimester missed abortion who underwent suction curettage with IV oxytocin administration were retrospectively reviewed. RESULTS: Among the patients, 67 received 10 IU of IV oxytocin before suction curettage (early-oxytocin administration group), while 79 patients received 10 IU of IV oxytocin after suction curettage (late-oxytocin administration group). The demographic features between the two groups did not significantly differ. However, there was a lower proportion of nulliparous patients in the early-oxytocin administration group than in the late-oxytocin administration group (38.8% vs 60.8%, p = 0.006). The perioperative blood loss amount was significantly lower in the early-oxytocin administration group than in the late-oxytocin administration group (60 [range: 50-100] vs 100 [range: 30-250] mL, p = 0.001). Moreover, the multivariate logistic regression analysis showed that the early-oxytocin administration group had a lower risk for a perioperative blood loss amount of ≥100 mL than the late-oxytocin administration group (0.23 [range: 0.10-0.55], p = 0.001); a gestational age of 9-12 weeks ( p = 0.009) was found to be associated with an increased risk for a perioperative blood loss amount of ≥100 mL. CONCLUSION: Compared with late-oxytocin administration, early-oxytocin administration could reduce perioperative blood loss during first-trimester suction curettage for missed abortion. However, the results require further investigation.

A Self-Assembled Matrix System for Cell-Bioengineering Applications in Different Dimensions, Scales, and Geometries.

Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation-mediated self-assembling mechanism, a biomatrix system optimal for 2D human mesenchymal stromal cell (hMSC) culture and osteogenesis is identified. Its utility for hMSC bioengineering is further demonstrated in coating porous bioactive glass scaffolds and nanoparticle synthesis for esiRNA delivery to knock down the SOX-9 gene with high delivery efficiency. The self-assembled injectable system is further utilized for 3D cell culture, segregated co-culture of hMSC with human umbilical vein endothelial cells (HUVEC) as an angiogenesis model, and 3D bioprinting. Most interestingly, the coating of bioactive glass with the self-assembled biomatrix not only supports the proliferation and osteogenesis of hMSC in the 3D scaffold but also induces the amorphous bioactive glass (BG) scaffold surface to form new apatite crystals resembling bone-shaped plate structures. Thus, the self-assembled biomatrix system can be utilized in various dimensions, scales, and geometries for many different bioengineering applications.

Se4P4nanoparticles confined within porous carbon as a lithium-ion battery anode with superior electrochemical performance.

The exploration of advanced anode materials through rational structure/phase design is the key to developing high-performance rechargeable batteries. Herein, tetraphosphorus tetraselenide (Se4P4) nanoparticles confined within porous carbon (named SeP@C) are developed for lithium-ion batteries. The designed SeP@C shows a set of structural/compositional advantages as lithium-ion battery anodes including high electrical conductivity, low ion diffusion barrier, and relieved lithiation stress. Consequently, the SeP@C electrode displays superior comprehensive lithium storage performance, e.g., high reversible capacity (640.8 mA h g-1at 0.1 A g-1), excellent cycling stability (500 cycles with respective capacity retention of over or nearly 100%), and good rate capability, representing a comparable lithium storage performance in reported phosphide-based anodes. More significantly, it shows excellent energy storage properties in lithium-ion full cells which can light up 85 red LEDs for over 3.2 h. This work offers an advanced electrode construction guidance of phosphorous-based anodes for the development of high-performance energy storage devices.

Controlling Surface Wettability for Automated In Situ Array Synthesis and Direct Bioscreening.

The in situ synthesis of biomolecules on glass surfaces for direct bioscreening can be a powerful tool in the fields of pharmaceutical sciences, biomaterials, and chemical biology. However, it is still challenging to 1) achieve this conventional multistep combinatorial synthesis on glass surfaces with small feature sizes and high yields and 2) develop a surface which is compatible with solid-phase syntheses, as well as the subsequent bioscreening. This work reports an amphiphilic coating of a glass surface on which small droplets of polar aprotic organic solvents can be deposited with an enhanced contact angle and inhibited motion to permit fully automated multiple rounds of the combinatorial synthesis of small-molecule compounds and peptides. This amphiphilic coating can be switched into a hydrophilic network for protein- and cell-based screening. Employing this in situ synthesis method, chemical space can be probed via array technology with unprecedented speed for various applications, such as lead discovery/optimization in medicinal chemistry and biomaterial development.

Adjunctive dexmedetomidine infusion in open living donor hepatectomy: A way to enhance postoperative analgesia and recovery.

BACKGROUND: Open living donor hepatectomy (OLDH) is a highly painful procedure. Advanced strategies for enhancing perioperative analgesia and accelerating recovery are needed for patients undergoing OLDH. This study evaluated the effects of intravenous infusion of dexmedetomidine (DEX) during OLDH on postoperative analgesia and recovery. METHODS: This prospective, randomised, double-blinded, and placebo-controlled study included 34 patients randomised to a control group (group C) and a DEX group (group D). Utilisation of intravenous patient-controlled analgesia (IV-PCA) pump, pain intensity, and postoperative recovery variables were recorded. Moreover, intraoperative anaesthetic consumption, hemodynamic parameters, and fluid status were also recorded. RESULTS: During the first 24 hours after surgery, patients in group D had a lower pain intensity. The cumulative numbers of IV-PCA pump presses and fentanyl consumption within 24 and 48 hours postoperatively in group C were significantly higher than in group D. The time to first IV-PCA attempt was prolonged in group D. In addition, faster flatus passage was observed in group D. Intraoperatively, fewer anaesthetic agents were required in group D. Less fluctuation in hemodynamics and reduced bleeding were also found in group D. CONCLUSIONS: The present study revealed that the addition of intravenous infusion of DEX during OLDH provided several benefits in relieving postoperative pain and promoting recovery. Therefore, we concluded that intraoperative DEX infusion may play an important role in enhancing the recovery of patients undergoing OLDH.

Comparison of maternal and fetal outcomes between delayed and immediate pushing in the second stage of vaginal delivery: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The second stage of labor begins with complete dilatation of the cervix until delivery of the fetus. After the cervix has fully dilated, the caregiver/nurse will provide guidance to the mother regarding the push technique for delivering the fetus (immediate pushing, IP). Because some women receive analgesic medications during labor, they might not be able to push correctly. Therefore, some obstetricians choose to postpone guiding the patient to push until the cervix is fully dilated and the fetal head has begun to descend. At this point, there is an involuntary exertion sensation (delayed pushing, DP) that saves energy and, at the same time, decreases tiredness and fatigue. The best timing for pushing during the second stage of labor is still controversial. The aim of this study was to investigate the different maternal and neonatal outcomes with IP and DP in the second stage of labor. METHODS: The Cochrane Library, EMBASE, PubMed, and Airiti Library (a Chinese database) were searched up to July 2019. Search keywords included: "labor stage, second", "delayed pushing", and "immediate pushing". Gray literature and bibliographies of articles were checked. No language restrictions were applied. Only randomized controlled trials were included. Two independent reviewers identified relevant studies and extracted data. The quality of the studies was assessed using the Cochrane's Risk of Bias tool. A random-effects meta-analysis was used to pool results. Mean differences and risk ratios were calculated with 95% confidence intervals (CIs) using Review Manager 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark, 2014). The risk of heterogeneity was reported as I2, and publication bias was visually assessed by funnel plots. RESULTS: In total, 15 studies (n = 6121 participants) were identified. Pooled results demonstrated the following. (1) As to maternal outcomes, in comparison, IP shortened the length of the second stage of labor by 40.9 (95% CI 23.6-58.2) min; however, DP decreased the total length of pushing by 25.4 (95% CI 13.9-37.0) min. The incidence of instrument-assisted vaginal delivery was significantly lower in the DP group in western countries (RR 0.85, 95% CI 0.74-0.97). In addition, the maternal postpartum fatigue score was 0.67 points lower in the DP group (95% CI - 1.09 to - 0.26). There was no statistical significance of the cesarean section rate or blood loss. (2) As to neonatal outcomes (Apgar score at 1 min), the DP group showed a higher score (by 0.19; 95% CI 0.10-0.27 points) than the IP group. CONCLUSIONS: Delayed pushing can decrease the total pushing time and decrease the fatigue score after delivery without significant adverse events compared to the early pushing group. Therefore, we recommend that caregivers instruct the pushing time at the optimal moment, which allows women to have more resting time and save energy during labor.

Does hyoscine N-butylbromide shorten the active phase in labor? A meta-analysis of randomized controlled trials.

OBJECTIVES: The objective of the study is to evaluate the therapeutic effect of hyoscine N-butylbromide (HBB) in active phase of labor and its safety to mother and fetus. METHODS: A systematic literature search was conducted on Cochrane Library, Pubmed, EMBASE, CINAHL, ClinicalTrials.gov and three databases in Chinese up to March 31, 2020. Randomized controlled trials (RCTs) of HBB administration during the active phase for shortening of spontaneous labor at term compared with placebo were included. Two reviewers assessed the methodological quality and data extraction independently. We calculated pooled risk ratios (RRs), mean differences (MDs) and 95% confidence intervals (CIs) using Review Manager 5.3 software. Intention-to-treat principles and random-effects model were adopted for analysis and pool results. RESULTS: In total, 1448 women from 9 RCTs were included in the meta-analysis. The HBB group exhibited significantly decreased durations of active phase (MD -61.1 min; 95% CI: -87.7 to -34.4, I2 : 96%), the second stage (MD -2.0 min; 95% CI: -3.4 to -0.5, I2 : 62%), and third stage (MD -0.7 min; 95% CI: -1.1 to -0.3, I2 : 51%). Intravenous (IV) HBB group and intramuscularly (IM) HBB group were compared to the control group (MD -60.9 min; 95% CI -87.7 to -34.1, I2 : 96%). No significant differences were observed in Cesarean section, post-partum hemorrhage, instrumental labor, Apgar scores or any adverse effects. CONCLUSION: Hyoscine N-butylbromide had a significant effect of shortening the duration of the active phase of labor without adverse effects. We recommend a single dose of intravenous administrated HBB when a woman undergoes labor augmentation.

Effects of lung protective ventilation on postoperative pulmonary outcomes for prolonged oral cancer combined with free flap surgery.

The intraoperative lung protective ventilation with low tidal volume, positive end expiratory pressure (PEEP) and intermittent lungs recruitment was found to decrease postoperative pulmonary complications. In this retrospective medical records study, we investigated the effects of lung protective ventilation on postoperative pulmonary outcomes among the patients received prolonged oral cancer combined with free flap surgery.We collected the medical records of the patients received oral cancer surgery with the operation time more than 12 hours from January 2011 to December 2015. We recordedFifty nine cases were included. Thirty cases received the lung protective ventilation and 29 cases received conventional ventilation. Compared to the patients received conventional ventilation, the patients received intraoperative lung protective ventilation showedIn conclusion, for the prolonged oral cancer combined with free flap surgery, the intraoperative lung protective ventilation improves postoperative pulmonary outcomes and decreases the duration of ICU stay.

Evaluation of thirty patients with eustachian tube dysfunction in Taiwan by questionnaire survey.

BACKGROUND: Eustachian tube dysfunction (ETD) is a common otolaryngological disorder. The seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was used for the assessment of symptoms related to ETD and treatment outcome. Currently, there is no traditional Chinese version of the ETDQ-7 to diagnose ETD in Taiwan. We aim to verify the reliability and validity of the traditional Chinese version of the ETDQ-7 in a clinical setting. METHODS: The traditional Chinese version of the ETDQ-7 was completed by 60 adult subjects composed of 30 healthy controls and 30 subjects diagnosed with ETD. The internal consistency was evaluated using the Cronbach's α coefficient. The discriminant validity was calculated by receiver operating characteristic (ROC) curve as an accuracy measure. RESULTS: The overall Cronbach's α coefficient of the traditional Chinese version ETDQ-7 was 0.717. The mean ETDQ-7 total score was 26.97 in the ETD group and 9.27 in the control group. The area under the ROC curve (AUC) was 99.8%, and the sensitivity and specificity of the traditional Chinese ETDQ-7 was 100% and 99.9%, respectively. CONCLUSION: The traditional Chinese version of the ETDQ-7 is a valid and reliable, disease-specific rating scale that can be used to quantitatively evaluate the severity of subjective symptoms of ETD in adult patients.

Using a PCR-Based Method To Analyze and Model Large, Heterogeneous Populations of DNA.

The study of populations of large size and high diversity is limited by the capability of collecting data. Moreover, for a pool of individuals, each associated with a unique characteristic feature, as the pool size grows, the possible interactions increase exponentially and quickly go beyond the limit of computation and experimental studies. Herein, the design of DNA libraries with various diversity is reported. By using a facile analytical method based on real-time PCR, the diversity of a pool of DNA can be evaluated to allow extraordinarily high heterogenicity (e.g., >1 trillion). It is demonstrated that these DNA libraries can be used to model heterogeneous populations; these libraries exhibit functions such as self-protection, suitability for biased expansion, and the possibility to evolve into amorphous structures. The method has shown the remarkable power of parallel computing with DNA, since it can resemble an analogue computer and be applied in selection-based biotechnology methods, such as DNA-encoded chemical libraries. As a chemical approach to solve problems traditionally for genetic and statistical analysis, the method provides a quick and cost-efficient evaluation of library diversity for intermediate steps through a selection process.

Modified transcanal cochlear implantation in CHARGE syndrome: A case report.

RATIONALE: Cochlear implantation (CI) in CHARGE syndrome is technically challenging because of the anatomical anomalies. This case aims to report a successful case of CI in CHARGE syndrome by using the modified transcanal approach with external auditory canal (EAC) obliteration. PATIENT CONCERNS: The 3-year-old girl presented at the outpatient department with bilateral hearing loss and nasal obstruction since birth. DIAGNOSIS: The patient had bilateral profound sensorineural hearing loss, patent ductus arteriosus, atresia of the choanae, middle and inner ear anomalies, and growth retardation, fulfilling the criteria for typical CHARGE syndrome. High resolution temporal bone computed tomography scan revealed a poorly developed mastoid cavity, cochlear dysplasia, hypoplastic semicircular canals, ossicular chain malformation, and sigmoid sinus engorgement. Magnetic resonance imaging revealed a narrow internal auditory canal and a hypoplastic cochlear nerve. INTERVENTIONS: Modified transcanal approach with external auditory canal obliteration OUTCOMES:: CI was successfully done and there are no intraoperative or postoperative complications occurred after 1 year of follow up. LESSONS: The modified transcanal approach is a reasonable and safer option for CI in CHARGE syndrome.

Propofol vs desflurane on the cytokine, matrix metalloproteinase-9, and heme oxygenase-1 response during living donor liver transplantation: A pilot study.

BACKGROUND: We investigated the effects of propofol vs desflurane on ischemia and reperfusion injury (IRI)-induced inflammatory responses, especially in matrix metalloproteinase-9 (MMP-9) downregulation and heme oxygenase-1 (HO-1) upregulation, which may result in different clinical outcomes in liver transplant recipients. METHODS: Fifty liver transplant recipients were randomized to receive propofol-based total intravenous anesthesia (TIVA group, n = 25) or desflurane anesthesia (DES group, n = 25). We then measured the following: perioperative serum cytokine concentrations (interleukin 1 receptor antagonist [IL-1RA], IL-6, IL-8, and IL-10); MMP-9 and HO-1 mRNA expression levels at predefined intervals. Further, postoperative outcomes were compared between the 2 groups. RESULTS: The TIVA group showed a significant HO-1 level increase following the anhepatic phase and a significant MMP-9 reduction after reperfusion, in addition to a significant increase in IL-10 levels after the anhepatic phase and IL-1RA levels after reperfusion. Compared to DES patients, TIVA patients showed a faster return of the international normalized ratio to normal values, lower plasma alanine aminotransferase concentrations 24 hours after transplantation, and fewer patients developing acute lung injury. Moreover, compared with DES patients, TIVA patients showed a significant reduction in serum blood lactate levels. However, there were no differences in postoperative outcomes between the two groups. CONCLUSION: Propofol-based TIVA attenuated inflammatory response (elevated IL-1RA and IL-10 levels), downregulated MMP-9 response, and increased HO-1 expression with improved recovery of graft function and better microcirculation compared with desflurane anesthesia in liver transplant recipients.

Fentanyl-based intravenous patient-controlled analgesia with low dose of ketamine is not inferior to thoracic epidural analgesia for acute post-thoracotomy pain following video-assisted thoracic surgery: A randomized controlled study.

BACKGROUND: Thoracic epidural analgesia is the preferred method for postoperative analgesia following thoracic surgery. However, intravenous patient-controlled analgesia (IVPCA) may be an effective alternative. This study was conducted because few scientific reports exist comparing fentanyl-based IVPCA including a low dose of ketamine (fk-IVPCA) with thoracic patient-controlled epidural analgesia (t-PCEA) for the treatment of postoperative pain after video-assisted thoracic surgery (VATS). METHODS: This prospective, and randomized study included 70 patients randomized into fk-IVPCA and t-PCEA groups. Pain at rest and during movement, successful and unsuccessful triggers after pressing the PCA device button, the need for rescue analgesia, drug-related adverse events, and patient satisfaction were recorded for 48 hours postoperatively. RESULTS: No significant differences in the intensity of pain at rest or during movement were observed between the 2 groups within 48 hours postoperatively. The number of unsuccessful PCA triggers in the t-PCEA group 0 to 4 hours after surgery was significantly higher than that in the fk-IVPCA group. However, the numbers of successful PCA triggers in the fk-IVPCA group at 4 to 12 and 0 to 24 hours after surgery were significantly higher than those in the t-PCEA group. The incidence of analgesic-related side effects and patient satisfaction were similar in both groups. CONCLUSIONS: Compared with t-PCEA, the addition of a subanesthetic dose of ketamine to fentanyl-based IVPCA resulted in similar pain control after VATS with no increase in the incidence of drug-related adverse effects. The results confirm that both multimodal intravenous analgesia and epidural analgesia can provide sufficient pain control and are safe strategies for treating acute post-thoracotomy pain.

Highly Conductive, Stretchable, and Cell-Adhesive Hydrogel by Nanoclay Doping.

Electrically conductive materials that mimic physical and biological properties of tissues are urgently required for seamless brain-machine interfaces. Here, a multinetwork hydrogel combining electrical conductivity of 26 S m-1 , stretchability of 800%, and tissue-like elastic modulus of 15 kPa with mimicry of the extracellular matrix is reported. Engineering this unique set of properties is enabled by a novel in-scaffold polymerization approach. Colloidal hydrogels of the nanoclay Laponite are employed as supports for the assembly of secondary polymer networks. Laponite dramatically increases the conductivity of in-scaffold polymerized poly(ethylene-3,4-diethoxy thiophene) in the absence of other dopants, while preserving excellent stretchability. The scaffold is coated with a layer containing adhesive peptide and polysaccharide dextran sulfate supporting the attachment, proliferation, and neuronal differentiation of human induced pluripotent stem cells directly on the surface of conductive hydrogels. Due to its compatibility with simple extrusion printing, this material promises to enable tissue-mimetic neurostimulating electrodes.