Zhao, Xuanhe

Current clinically used electronic implants, including cardiac pacing leads for epicardial monitoring and stimulation of the heart, rely on surgical suturing or direct insertion of electrodes to the heart tissue. These approaches can cause tissue trauma during the implantation and retrieval of the pacing leads, with the potential for bleeding, tissue damage, and device failure. Here, we report a bioadhesive pacing lead that can directly interface with cardiac tissue through physical and covalent interactions to support minimally invasive adhesive implantation and gentle on-demand removal of the device with a detachment solution. We developed 3D-printable bioadhesive materials for customized fabrication of the device by graft-polymerizing polyacrylic acid on hydrophilic polyurethane and mixing with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) to obtain electrical conductivity. The bioadhesive construct exhibited mechanical properties similar to cardiac tissue and strong tissue adhesion, supporting stable electrical interfacing. Infusion of a detachment solution to cleave physical and covalent cross-links between the adhesive interface and the tissue allowed retrieval of the bioadhesive pacing leads in rat and porcine models without apparent tissue damage. Continuous and reliable cardiac monitoring and pacing of rodent and porcine hearts were demonstrated for 2 weeks with consistent capture threshold and sensing amplitude, in contrast to a commercially available alternative. Pacing and continuous telemetric monitoring were achieved in a porcine model. These findings may offer a promising platform for adhesive bioelectronic devices for cardiac monitoring and treatment.

Continuous imaging of internal organs over days could provide crucial information about health and diseases and enable insights into developmental biology. We report a bioadhesive ultrasound (BAUS) device that consists of a thin and rigid ultrasound probe robustly adhered to the skin via a couplant made of a soft, tough, antidehydrating, and bioadhesive hydrogel-elastomer hybrid. The BAUS device provides 48 hours of continuous imaging of diverse internal organs, including blood vessels, muscle, heart, gastrointestinal tract, diaphragm, and lung. The BAUS device could enable diagnostic and monitoring tools for various diseases.

Surgical sealing and repair of injured and resected gastrointestinal (GI) organs are critical requirements for successful treatment and tissue healing. Despite being the standard of care, hand-sewn closure of GI defects using sutures faces limitations and challenges. In this work, we introduce an off-the-shelf bioadhesive GI patch capable of atraumatic, rapid, robust, and sutureless repair of GI defects. The GI patch integrates a nonadhesive top layer and a dry, bioadhesive bottom layer, resulting in a thin, flexible, transparent, and ready-to-use patch with tissue-matching mechanical properties. The rapid, robust, and sutureless sealing capability of the GI patch is systematically characterized using ex vivo porcine GI organ models. In vitro and in vivo rat models are used to evaluate the biocompatibility and degradability of the GI patch in comparison to commercially available tissue adhesives (Coseal and Histoacryl). To validate the GI patch’s efficacy, we demonstrate successful sutureless in vivo sealing and healing of GI defects in rat colon, stomach, and small intestine as well as in porcine colon injury models. The proposed GI patch provides a promising alternative to suture for repair of GI defects and offers potential clinical opportunities for the repair of other organs.

AbstractFor decades, bioadhesive materials have garnered great attention due to their potential to replace sutures and staples for sealing tissues during minimally invasive surgical procedures. However, the complexities of delivering bioadhesives through narrow spaces and achieving strong adhesion in fluid‐rich physiological environments continue to present substantial limitations to the surgical translation of existing sealants. In this work, a new strategy for minimally invasive tissue sealing based on a multilayer bioadhesive patch, which is designed to repel body fluids, to form fast, pressure‐triggered adhesion with wet tissues, and to resist biofouling and inflammation is introduced. The multifunctional patch is realized by a synergistic combination of three distinct functional layers: i) a microtextured bioadhesive layer, ii) a dynamic, blood‐repellent hydrophobic fluid layer, and iii) an antifouling zwitterionic nonadhesive layer. The patch is capable of forming robust adhesion to tissue surfaces in the presence of blood, and exhibits superior resistance to bacterial adhesion, fibrinogen adsorption, and in vivo fibrous capsule formation. By adopting origami‐based fabrication strategies, it is demonstrated that the patch can be readily integrated with a variety of minimally invasive end effectors to provide facile tissue sealing in ex vivo porcine models, offering new opportunities for minimally invasive tissue sealing in diverse clinical scenarios.

AbstractThromboembolic and infectious complications stemming from the use of cardiovascular medical devices are still common and result in significant morbidity and mortality. There is no strategy to date that effectively addresses both challenges at the same time. Various surface modification strategies (e.g., silver, heparin, and liquid‐impregnated surfaces) are proposed yet each has several limitations and shortcomings. Here, it is shown that the incorporation of an ultrathin and mechanically robust hydrogel layer reduces bacterial adhesion to medical‐grade tubing by 95%. It is additionally demonstrated, through a combination of in vitro and in vivo tests, that the hydrogel layer significantly reduces the formation and adhesion of blood clots to the tubing without affecting the blood's intrinsic clotting ability. The adhesion of clots to the tubing walls is reduced by over 90% (in vitro model), which results in an ≈60% increase in the device occlusion time (time before closure due to clot formation) in an in vivo porcine model. The advantageous properties of this passive coating make it a promising surface material candidate for medical devices interfacing with blood.

Significance Owing to potential advantages including ease of use, airtight or watertight sealing, and minimal tissue damage, bioadhesives have been intensively studied and developed as an alternative to sutures and staples to close wounds, achieve hemostasis, and attach and immobilize implantable devices. However, existing bioadhesives have limitations including slow adhesion formation, weak bonding, low biocompatibility, poor mechanical match with tissues, and/or lack of triggerable benign detachment. In this work, we report a bioadhesive capable of instant tough adhesion and triggerable benign detachment that can potentially address all the above-mentioned limitations. The current work not only develops a bioadhesive with superior performances but also advances the understanding of wet adhesion.

Abstract Slippery and hydrophilic surfaces find critical applications in areas as diverse as biomedical devices, microfluidics, antifouling, and underwater robots. Existing methods to achieve such surfaces rely mostly on grafting hydrophilic polymer brushes or coating hydrogel layers, but these methods suffer from several limitations. Grafted polymer brushes are prone to damage and do not provide sufficient mechanical compliance due to their nanometer‐scale thickness. Hydrogel coatings are applicable only for relatively simple geometries, precluding their use for the surfaces with complex geometries and features. Here, a new method is proposed to interpenetrate hydrophilic polymers into the surface of diverse polymers with arbitrary shapes to form naturally integrated “hydrogel skins.” The hydrogel skins exhibit tissue‐like softness (Young's modulus ≈ 30 kPa), have uniform and tunable thickness in the range of 5–25 µm, and can withstand prolonged shearing forces with no measurable damage. The hydrogel skins also provide superior low‐friction, antifouling, and ionically conductive surfaces to the polymer substrates without compromising their original mechanical properties and geometry. Applications of the hydrogel skins on inner and outer surfaces of various practical polymer devices including medical tubing, Foley catheters, cardiac pacemaker leads, and soft robots on massive scales are further demonstrated.