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In drug discovery, human organ-on-a-chip (organ chip) technology has emerged as an essential tool for preclinical testing, offering a realistic representation of human physiology, real-time monitoring, and disease modeling. Polydimethylsiloxane (PDMS) is commonly used in organ chip fabrication owing to its biocompatibility, flexibility, transparency, and ability to replicate features down to the nanoscale. However, the porous nature of PDMS leads to unintended absorption of small molecules, critically affecting the drug response analysis. Addressing this challenge, the precision drug testing organ chip (PreD chip) is introduced, an innovative platform engineered to minimize small molecule absorption while facilitating cell culture. This chip features a PDMS microchannel wall coated with a perfluoropolyether-based lubricant, providing slipperiness and antifouling properties. It also incorporates an ECM-coated semi-porous membrane that supports robust multicellular cultures. The PreD chip demonstrates its outstanding antifouling properties and resistance to various biological fluids, small molecule drugs, and plasma proteins. In simulating the human gut barrier, the PreD chip demonstrates highly enhanced sensitivity in tests for dexamethasone toxicity and is highly effective in assessing drug transport across the human blood-brain barrier. These findings emphasize the potential of the PreD chip in advancing organ chip-based drug testing methodologies.
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Accurate postoperative assessment of varying mechanical properties is crucial for customizing patient-specific treatments and optimizing rehabilitation strategies following Achilles tendon (AT) rupture and reconstruction surgery. This study introduces a wireless, chip-less, and immune-tolerant in vivo strain-sensing suture designed to continuously monitor mechanical stiffness variations in the reconstructed AT throughout the healing process. This innovative sensing suture integrates a standard medical suturing thread with a wireless fiber strain-sensing system, which incorporates a fiber strain sensor and a double-layered inductive coil for wireless readout. The winding design of Au nanoparticle-based fiber electrodes and a hollow core contribute to the fiber strain sensor's high sensitivity (factor of 6.2 and 15.1 pF for revised sensitivity), negligible hysteresis, and durability over 10,000 stretching cycles. To ensure biocompatibility and immune tolerance during extended in vivo periods, an antibiofouling lubricant layer was applied to the sensing suture. Using this sensing system, we successfully monitored the strain responses of the reconstructed AT in an in vivo porcine model. This facilitated the postoperative assessment of mechanical stiffness variations through a well-established analytical model during the healing period.
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Materiales Biocompatibles , Suturas , Tecnología Inalámbrica , Tecnología Inalámbrica/instrumentación , Animales , Porcinos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Tendón Calcáneo , Oro/química , Nanopartículas del Metal/químicaRESUMEN
BACKGROUND: The aim of this study was to examine the specific characteristics of injuries (injury location, injury type, and time to return to sports) based on sex and rowing style. METHODS: We included 60 adolescent rowers (Sweep male and female, 12 respectively; Sculling male and female, 18 respectively) who underwent training in Korea from January to December 2023. Sports injuries were meticulously recorded using the Daily Injury Report form issued by the International Olympic Committee for rowers characteristics (sex, rowing style) and injury characteristics (injury location, injury type). The injury incidence rate (IIR) per 1000 h of training was calculated using the 95% Poisson Confidence Interval. A χ2 test was performed to compare the characteristics of the rowers and injury characteristics. RESULTS: The overall IIR was 4.25 injuries per 1000 training hours. The IIR was lower for men than for women (P<0.001). However, sweep and sculling were similar (P=0.269). There was a difference in the affected body regions according to the sex and rowing style (P=0.028, P=0.005; respectively). Time to return to sports varied between rowing styles (P=0.049) and sexes (P=0.033), and it also differed in sweep (P=0.002) and sculling (P=0.045) depending on body regions. CONCLUSIONS: These results should be incorporated into programs that are aimed at improving the performance of these rowers and preventing sports injuries. In addition, can be used as data to determine their return to sport.
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Seamless integration and conformal contact of soft electronics with tissue surfaces have emerged as major challenges in realizing accurate monitoring of biological signals. However, the mechanical mismatch between the electronics and biological tissues impedes the conformal interfacing between them. Attempts have been made to utilize soft hydrogels as the bioelectronic materials to realize tissue-comfortable bioelectronics. However, hydrogels have several limitations in terms of their electrical and mechanical properties. In this study, we present the development of a 3D-printable modulus-tunable hydrogel with multiple functionalities. The hydrogel has a cross-linked double network, which greatly improves its mechanical properties. Functional fillers such as XLG or functionalized carbon nanotubes (fCNT) can be incorporated into the hydrogel to provide tunable mechanics (Young's modulus of 10-300 kPa) and electrical conductivity (electrical conductivity of â¼20 S/m). The developed hydrogel exhibits stretchability (â¼1000% strain), self-healing ability (within 5 min), toughness (400-731 kJ/m3) viscoelasticity, tissue conformability, and biocompatibility. Upon examining the rheological properties in the modulated region, hydrogels can be 3D printed to customize the shape and design of the bioelectronics. These hydrogels can be fabricated into ring-shaped strain sensors for wearable sensor applications.
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Técnicas Biosensibles , Nanotubos de Carbono , Hidrogeles , Tinta , Conductividad Eléctrica , Electrónica , Impresión TridimensionalRESUMEN
Hydrogels have the potential to play a crucial role in bioelectronics, as they share many properties with human tissues. However, to effectively bridge the gap between electronics and biological systems, hydrogels must possess multiple functionalities, including toughness, stretchability, self-healing ability, three-dimensional (3D) printability, and electrical conductivity. Fabricating such tough and self-healing materials has been reported, but it still remains a challenge to fulfill all of those features, and in particular, 3D printing of hydrogel is in the early stage of the research. In this paper, we present a 3D printable, tough, and self-healing multi-functional hydrogel in one platform made from a blend of poly(vinyl alcohol) (PVA), tannic acid (TA), and poly(acrylic acid) (PAA) hydrogel ink (PVA/TA/PAA hydrogel ink). Based on a reversible hydrogen-bond (H-bond)-based double network, the developed 3D printable hydrogel ink showed excellent printability via shear-thinning behavior, allowing high printing resolution (~100 µm) and successful fabrication of 3D-printed structure by layer-by-layer printing. Moreover, the PVA/TA/PAA hydrogel ink exhibited high toughness (tensile loading of up to ~45.6 kPa), stretchability (elongation of approximately 650%), tissue-like Young's modulus (~15 kPa), and self-healing ability within 5 min. Furthermore, carbon nanotube (CNT) fillers were successfully added to enhance the electrical conductivity of the hydrogel. We confirmed the practicality of the hydrogel inks for bioelectronics by demonstrating biocompatibility, tissue adhesiveness, and strain sensing ability through PVA/TA/PAA/CNT hydrogel ink.
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Coronary artery bypass grafting is commonly used to treat cardiovascular diseases by replacing blocked blood vessels with autologous or artificial blood vessels. Nevertheless, the availability of autologous vessels in infants and the elderly and low long-term patency rate of grafts hinder extensive application of autologous vessels in clinical practice. The biological and mechanical properties of the resealable antithrombotic artificial vascular graft (RAAVG) fabricated herein, comprising a bioelectronic conduit based on a tough self-healing polymer (T-SHP) and a lubricious inner coating, match with the functions of autologous blood vessels. The self-healing and elastic properties of the T-SHP confer resistance against mechanical stimuli and promote conformal sealing of suturing regions, thereby preventing leakage (stable fixation under a strain of 50%). The inner layer of the RAAVG presents antibiofouling properties against blood cells and proteins, and antithrombotic properties, owing to its lubricious coating. Moreover, the blood-flow sensor fabricated using the T-SHP and carbon nanotubes is seamlessly integrated into the RAAVG via self-healing and allows highly sensitive monitoring of blood flow at low and high flow rates (10- and 100 mL min-1, respectively). Biocompatibility and feasibility of RAAVG as an artificial graft were demonstrated via ex vivo, and in vivo experiment using a rodent model. The use of RAAVGs to replace blocked blood vessels can improve the long-term patency rate of coronary artery bypass grafts.
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Fibrinolíticos , Nanotubos de Carbono , HemodinámicaRESUMEN
Implantable biomedical devices require an anti-biofouling, mechanically robust, low friction surface for a prolonged lifespan and improved performance. However, there exist no methods that could provide uniform and effective coatings for medical devices with complex shapes and materials to prevent immune-related side effects and thrombosis when they encounter biological tissues. Here, we report a lubricant skin (L-skin), a coating method based on the application of thin layers of bio-adhesive and lubricant-swellable perfluoropolymer that impart anti-biofouling, frictionless, robust, and heat-mediated self-healing properties. We demonstrate biocompatible, mechanically robust, and sterilization-safe L-skin in applications of bioprinting, microfluidics, catheter, and long and narrow medical tubing. We envision that diverse applications of L-skin improve device longevity, as well as anti-biofouling attributes in biomedical devices with complex shapes and material compositions.
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Developing bioelectronics that retains their long-term functionalities in the human body during daily activities is a current critical issue. To accomplish this, robust tissue adaptability and biointerfacing of bioelectronics should be achieved. Hydrogels have emerged as promising materials for bioelectronics that can softly adapt to and interface with tissues. However, hydrogels lack toughness, requisite electrical properties, and fabrication methodologies. Additionally, the water-swellable property of hydrogels weakens their mechanical properties. In this work, an intrinsically nonswellable multifunctional hydrogel exhibiting tissue-like moduli ranging from 10 to 100 kPa, toughness (400-873 J m-3 ), stretchability (≈1000% strain), and rapid self-healing ability (within 5 min), is developed. The incorporation of carboxyl- and hydroxyl-functionalized carbon nanotubes (fCNTs) ensures high conductivity of the hydrogel (≈40 S m-1 ), which can be maintained and recovered even after stretching or rupture. After a simple chemical modification, the hydrogel shows tissue-adhesive properties (≈50 kPa) against the target tissues. Moreover, the hydrogel can be 3D printed with a high resolution (≈100 µm) through heat treatment owing to its shear-thinning capacity, endowing it with fabrication versatility. The hydrogel is successfully applied to underwater electromyography (EMG) detection and ex vivo bladder expansion monitoring, demonstrating its potential for practical bioelectronics.
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Hidrogeles , Nanotubos de Carbono , Humanos , Hidrogeles/química , Nanotubos de Carbono/química , Conductividad EléctricaRESUMEN
Surgical sutures are widely used for closing wounds in skin. However, the monitoring of wound integrity and promoting tissue regeneration at the same time still remains a challenge. To address this, we developed a drug-releasing electronic suture system (DRESS) to monitor the suture integrity in real-time and enhance tissue regeneration by triggered drug release. DRESS was fabricated by using a single fiber with a core-shell structure consisting of a stretchable conductive fiber core and a thermoresponsive polymer shell containing drugs. The highly conductive fiber core acts as a strain sensor that enables continuous monitoring of suture strain with high sensitivity (a gauge factor of â¼686) and mechanical durability (being able to endure more than 3000 stretching cycles). The thermoresponsive shell layer composed of flexible poly(vinyl alcohol) (PVA) grafted onto poly(N-isopropylacrylamide) (PNIPAm) facilitates on-demand drug release via Joule heating. The results of an in vitro scratch assay showed a 66% decrease in wound area upon heat-activation after 48 hours demonstrating the stimuli-responsive therapeutic efficacy of DRESS by promoting cell migration. Moreover, ex vivo testing on porcine skin demonstrated the applicability of DRESS as a electronic suture. The approach used for DRESS provides insight into multifunctional sutures and offers additional therapeutic and diagnostic options for clinical applications.
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Electrónica , Suturas , Liberación de Fármacos , Conductividad Eléctrica , Cicatrización de HeridasRESUMEN
Recent advances in diagnostics and medicines emphasize the spatial and temporal aspects of monitoring and treating diseases. However, conventional therapeutics, including oral administration and injection, have difficulties meeting these aspects due to physiological and technological limitations, such as long-term implantation and a narrow therapeutic window. As an innovative approach to overcome these limitations, electronic devices known as electronic drugs (e-drugs) have been developed to monitor real-time body signals and deliver specific treatments to targeted tissues or organs. For example, ingestible and patch-type e-drugs could detect changes in biomarkers at the target sites, including the gastrointestinal (GI) tract and the skin, and deliver therapeutics to enhance healing in a spatiotemporal manner. However, medical treatments often require invasive surgical procedures and implantation of medical equipment for either short or long-term use. Therefore, approaches that could minimize implantation-associated side effects, such as inflammation and scar tissue formation, while maintaining high functionality of e-drugs, are highly needed. Herein, the importance of the spatial and temporal aspects of medical treatment is thoroughly reviewed along with how e-drugs use cutting-edge technological innovations to deal with unresolved medical challenges. Furthermore, diverse uses of e-drugs in clinical applications and the future perspectives of e-drugs are discussed.
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ElectrónicaRESUMEN
Bacterial infection and infection-induced immune response have been a life-threatening risk for patients having orthopedic implant surgeries. Conventional biomaterials are vulnerable to biocontamination, which causes bacterial invasion in wounded areas, leading to postoperative infection. Therefore, development of anti-infection and immune-evasive coating for orthopedic implants is urgently needed. Here, we developed an advanced surface modification technique for orthopedic implants termed lubricated orthopedic implant surface (LOIS), which was inspired by slippery surface of Nepenthes pitcher plant. LOIS presents a long-lasting, extreme liquid repellency against diverse liquids and biosubstances including cells, proteins, calcium, and bacteria. In addition, we confirmed mechanical durability against scratches and fixation force by simulating inevitable damages during surgical procedure ex vivo. The antibiofouling and anti-infection capability of LOIS were thoroughly investigated using an osteomyelitis femoral fracture model of rabbits. We envision that the LOIS with antibiofouling properties and mechanical durability is a step forward in infection-free orthopedic surgeries.
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While a clear operating field during endoscopy is essential for accurate diagnosis and effective surgery, fogging or biofouling of the lens can cause loss of visibility during these procedures. Conventional cleaning methods such as the use of an irrigation unit, anti-fogging surfactant, or particle-based porous coatings infused with lubricants have been used but proven insufficient to prevent loss of visibility. Herein, a mechanically robust anti-fogging and anti-biofouling endoscope lens was developed by forming a lubricant-infused directly engraved nano-/micro-structured surface (LIDENS) on the lens. This structure was directly engraved onto the lens via line-by-line ablation with a femtosecond laser. This directly engraved nano/microstructure provides LIDENS lenses with superior mechanical robustness compared to lenses with conventional particle-based coatings, enabling the maintenance of clear visibility throughout typical procedures. The LIDENS lens was chemically modified with a fluorinated self-assembled monolayer (F-SAM) followed by infusion of medical-grade perfluorocarbon lubricants. This provides the lens with high transparency (> 70%) along with superior and long-lasting repellency towards various liquids. This excellent liquid repellency was also shown to be maintained during blood dipping, spraying, and droplet condensation experiments. We believe that endoscopic lenses with the LIDENS offer excellent benefits to endoscopic surgery by securing clear visibility for stable operation.
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Biocompatible, electrically conductive microfibers with superior mechanical properties have received a great attention due to their potential applications in various biomedical applications such as implantable medical devices, biosensors, artificial muscles, and microactuators. Here, we developed an electrically conductive and mechanically stable carbon nanotube-based microactuator with a low degradability that makes it usable for an implantable device in the body or biological environments. The microfiber was composed of hyaluronic acid (HA) hydrogel and single-wall carbon nanotubes (SWCNTs) (HA/SWCNT). HA hydrogel acts as biosurfactant and ion-conducting binder to improve the dispersion of SWCNTs resulting in enhanced electrical and mechanical properties of the hybrid microfiber. In addition, HA was crosslinked to prevent the leaking of the nanotubes from the composite. Crosslinking of HA hydrogel significantly enhances Young's modulus, the failure strain, the toughness, the stability of the electrical conductivity, and the resistance to biodegradation and creep of hybrid microfibers. The obtained crosslinked HA/SWCNT hybrid microfibers show an excellent capacitance and actuation behavior under mechanical loading with a low potential of ±1 V in a biological environment. Furthermore, the HA/SWCNT microfibers exhibit an excellent in vitro viability. Finally, the biocompatibility is shown through the resolution of an early inflammatory response in less than 3 weeks after the implantation of the microfibers in the subcutaneous tissue of mice.
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Major concerns in the development of wearable textile electronics are exposure to moisture and contamination. The exposure can cause electrical breakdown of the device and its interconnections, and thus continuous efforts have been made to fabricate textile electronics which are free from moisture and pollution. Herein, we developed a highly conductive and waterproof fiber with excellent electrical conductivity (0.11 Ω/cm) and mechanical stability for advanced interconnector components in wearable textile electronics. The fabrication process of the highly conductive fiber involves coating of a commercial Kevlar fiber with Ag nanoparticle-poly(styrene- block-butadiene- block-styrene) polymer composites. The fabricated fiber then gets treated with self-assembled monolayer (SAM)-forming reagents, which yields waterproof and self-cleaning properties. To find optimal SAM-forming reagents, four different kinds of reagents involving 1-decane thiol (DT), 1 H,1 H,2 H,2 H-perfluorohexanethiol, 1 H,1 H,2 H,2 H-perfluorodecyltrichlorosilane, 1 H,1 H,2 H,2 H-perfluodecanethiol (PFDT) were compared in terms of their thiol group and carbon chain lengths. Among the SAM-forming reagents, the PFDT-treated conductive fiber showed superior waterproof and self-cleaning property, as well as great sustainability in the water with varying pH because of nanoscale roughness and low surface energy. In addition, the functionality of the conductive fiber was tested under mechanical compression via repeated washing and folding processes. The developed conductive fiber with waterproof and self-cleaning property has promising applications in the interconnector operated under water and textile electronics.
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In the last decades, bioengineers have developed myriad biomaterials for regenerative medicine. Development of screening techniques is essential for understanding complex behavior of cells in the biological microenvironments. Conventional approaches to the screening of cellular behavior in vitro have limitations in terms of accuracy, reusability, labor-intensive screening, and versatility. Thus, drug screening and toxicology test through in vitro screening platforms have been underwhelming. Recent advances in the high-throughput screening platforms somewhat overcome the limitations of in vitro screening platforms via repopulating human tissues' biophysical and biomchemical microenvironments with the ability to continuous monitoring of miniaturized human tissue behavior. Herein, we review current trends in the screening platform in which a high-throughput system composed of engineered microarray devices is developed to investigate cell-biomaterial interaction. Furthermore, diverse methods to achieve continuous monitoring of cell behavior via developments of biosensor integrated high-throughput platforms, and future perspectives on high-throughput screening will be provided.