For addressing the challenges regarding muscle injuries, 3D printing has been a promising technique to fabricate patient-specific scaffolds and effectively guide myotube alignment. Although methacrylate-conjugated gelatin (GelMA) is widely used as an ink material for 3D printing because of its facile photo-crosslinking and cell-adhesive properties, its intrinsic low viscosity and weak mechanics require high concentrations of the polymer for 3D printing and matching with tissue-like modulus, while its limited tissue adhesion further restricts its applicability in on-muscle printing. In this study, we propose a printable and bioadhesive hydrogel ink (PBAink) with low polymer concentration of alginate tethered with phenylborate and methacrylate (AlMABA), which exhibits a storage modulus similar to that of muscle tissues and undergoes rapid crosslinking within 90 s under blue light irradiation, making it suitable for 3D printing. Additionally, it exhibits low swelling under physiological conditions and good biocompatibility, owing to its excellent hydrophilic properties imparted by phenylborate groups, making it a suitable material for direct on-muscle printing. Notably, because dynamic bonds between cis-diols and phenylborate groups are formed in phosphate-buffered saline environments, we optimized the salt concentration of the buffer solution mixed with AlMABA to enhance cohesion; this led to the development of PBAink, which enhanced fidelity of printing at low concentrations, while the methacrylate groups ensured structural stability via photo-crosslinking. Moreover, PBAink exhibits tissue-adhesive properties compared with methacrylate-conjugated alginate and GelMA, supporting the direct on-muscle printing and conformal integration of the printed hydrogel with the muscle tissue. The PBAink exhibited intriguing cell-adhesive properties, inducing C2C12 clustering, while also promoting cell spreading. Finally, these features contributed to increased cell density and enhanced F-actin coverage on 3D-printed PBAink scaffolds, thereby highlighting its potential as an effective alternative to conventional GelMA-based inks.

Conventional neuroprosthetic interfaces rely on rigid and bulky structures, which limit long-term systemic operations. For chronic applications of neural interfaces targeting regions of the nervous system (brain, spinal cord, and peripheral nerves), maintaining stable electrical performance of alternative devices without physical pressure or secondary damage to nerve tissues is important. Soft neural interfaces based on intrinsically stretchable nanocomposites, functional nanomaterials embedded in a strain-durable polymer matrix, represent ideal platforms due to their spontaneous mechanical modulus matching with biological tissues, enabling a stable device-tissue interface for high-fidelity signaling. A purpose-driven feedback system operating in a closed-loop manner is desirable to supplement artificial bidirectional sensory-motor pathways, as the ultimate goal is to restore sensory and motor functions similar to those of able-bodied individuals. We present recent advancements in material strategies, structural device designs, and monolithic integration of personalized closed-loop neuroprostheses. This includes an overview of soft bioelectronic materials and device platforms featuring high stretchability, conformability, electrical durability and recovery, and tissue adhesion. Strain-gradient bilayer structures combining functional nanocomposite electrodes and tissue-adhesive hydrogel layers have been highlighted as optimal tissue-interfacing form factors. We suggest future directions for monolithically integrated soft neuroprosthetic systems aimed at the personalized treatment of patients with impaired neural function.

The need for the development of soft materials capable of stably adhering to nerve tissues without any suturing followed by additional damages is at the fore at a time when success in postoperative recovery depends largely on the surgical experience and/or specialized microsuturing skills of the surgeon. Despite fully recognizing such prerequisite conditions, designing the materials with robust adhesion to wet nerves as well as acute/chronic anti-inflammation remains to be resolved. Herein, a sticky and strain-gradient artificial epineurium (SSGAE) that overcomes the most critically challenging aspect for realizing sutureless repair of severely injured nerves is presented. In this regard, the SSGAE with a skin-inspired hierarchical structure entailing strain-gradient layers, anisotropic Janus layers including hydrophobic top and hydrophilic bottom surfaces, and synergistic self-healing capabilities enables immediate and stable neurorrhaphy in both rodent and nonhuman primate models, indicating that the bioinspired materials strategy significantly contributes to translational medicine for effective peripheral nerve repair.

Implantable electrochemicals stand out as promising candidates for resolving peripheral nerve injuries. However, challenges persist in designing bioelectronic materials that mimic tissue due to modulus matching, conformal adhesion, and immune responses. Herein, we present a nerve-mimicking design rationale for biocompatible hydrogel-based electroceuticals with a tissue-like modulus, robust and conformal tissue adhesion, exceptional mechanical toughness, and efficient stress dissipation. Inspired by the hierarchical structure of the peripheral nerve, the hydrogel substrate features a structurally gradient bilayer transitioning from a dense to a loose polymeric network, utilizing alginate functionalized with either photo-cross-linkable methacrylate or tissue-adhesive phenylborate. Due to the varying water affinity of the tethering groups, a physically entangled interfacial domain is in situ formed during dehydration of the pre-gel film, resulting in enhanced mechanical toughness and strong adhesion. The hydrogel electroceuticals, when integrated with conducting polymeric electrodes, locally stimulate nerve tissue, improving tissue regeneration in a crushed nerve injury model.

Achieving long-term stable monitoring of neural signals and on-demand feedback electrical stimulation in a closed-loop manner is essential for personalized diagnosis and treatment of neurological disorders. In addition, stiffness of tissue-interfacing electrodes utilized during bidirectional signaling operations should be mechanically adaptive to the peripheral nerves for preventing undesired tissue compression. However, challenges remain associated with absence of tissue adhesion and cyclic stretching durability of the conventional soft electrodes, leading to unstable device–tissue interactions. Here, we developed a nerve-adhesive stretchable electrode (NSE) that is capable of stably monitoring sensory neural signals and electrical modulation. The NSE consists of a tough self-healing polymer substrate, an ultrathin stretchable polyimide-Au-polyimide electrode, and a mussel-inspired wet tissue-adhesive hydrogel layer (alginate conjugated with boronic acid, Alg-BA). The Alg-BA enabled the NSE to be reliably attached to the sciatic nerve of a rat, while significantly improving its signal-to-noise ratios. In addition, the dynamic stress relaxation of the NSE was highly beneficial for mechanical adaptation to the nerve, featuring the long-term tissue safety even after implantation for eight weeks. The synergistic use of tissue-adhesive materials coupled with the stretchable electronic devices would provide a great opportunity to develop the advanced neural prostheses. Soft stretchable electrodes have been extensively developed for achieving long-term stable peripheral neural interfacing owing to their strain-insensitive bidirectional signaling performance. Although the conventional electrodes were highly effective in measuring neural signals and providing sensory feedback in patients with limb nerve damage or amputations, they were easily slipped from the original position on the nerve surface due to absence of a tissue adhesion property. The challenge has led to inaccurate interpretation of numerous sensory/motor information obtained from high-density multichannel electrodes as well as inflammation originating from occurrence of shear stress at the device–nerve interface. In this regard, the tissue adhesion is essential to provide the long-term stable neural interfacing. To address the unmet needs, wet-adhesive hydrogel materials should be integrated with the conventional stretchable electrodes. This article reports a promising strategy for realizing the chronic nerve-interfacing electrodes without causing device-tissue detachment or mechanical compression issues. The nerve-adhesive electrode consisting of a wet hydrogel, a self-healing polymeric substrate, and a stretchable Au nanomembrane was easily implanted to a sciatic nerve of a rodent model without using a conventional suturing process. The period of implantation of the nerve-adhesive electrode was almost finalized within 60 s, leading to a dramatic decrease in surgical deviations based on the surgeon’s expertise as well as an alleviation of surgery complexity. It is highly expected that development of the tissue-adhesive stretchable electrode would be the key solution for achieving future human–machine interface and personalized neural prostheses.

AbstractColorectal cancer is one of the most common cancers, and current treatment options include surgery, chemotherapy, and radiation therapy. Most patients undergo surgery, which often requires extensive resection of the colon to prevent recurrence and metastasis of residual malignant tumor cells, leading to postoperative pain and discomfort in daily routines. Although versatile therapeutic patches have been developed to induce tumor apoptosis, achieving both great adhesiveness on the mucus layers of the colon tissue and anti‐cell/tissue adhesion to other surrounding organs remains a challenge. Herein, we report a Janus polysaccharide film comprising two polymers: mussel‐inspired catechol‐conjugated chitosan (Chi‐C) with muco‐adhesiveness, and alginate (Alg) with anti‐adhesion property. The Chi‐C and Alg polymers form a stably entangled bilayer film via electrostatic interactions. The Janus film shows a strong tissue adhesive strength of ∼10 kPa for the Chi‐C layer and weak strength of ∼1 kPa for the Alg layer. Particularly, the Janus film encapsulating an anti‐cancer drug exhibits a directional release profile to the tumor site, which is effective for triggering tumor death in in vivo colorectal tumor resection model. Ultimately, such anti‐cancer material strategies using bilayered structures are promising for advanced tumor therapy.

In wearable bioelectronics, various studies have focused on enhancing prosthetic control accuracy by improving the quality of physiological signals. The fabrication of conductive composites through the addition of metal fillers is one way to achieve stretchability, conductivity, and biocompatibility. However, it is difficult to measure stable biological signals using these soft electronics during physical activities because of the slipping issues of the devices, which results in the inaccurate placement of the device at the target part of the body. To address these limitations, it is necessary to reduce the stiffness of the conductive materials and enhance the adhesion between the device and the skin. In this study, we measured the electromyography (EMG) signals by applying a three-layered hydrogel structure composed of chitosan-alginate-chitosan (CAC) to a stretchable electrode fabricated using a composite of styrene-ethylene-butylene-styrene and eutectic gallium-indium. We observed stable adhesion of the CAC hydrogel to the skin, which aided in keeping the electrode attached to the skin during the subject movement. Finally, we fabricated a multichannel array of CAC-coated composite electrodes (CACCE) to demonstrate the accurate classification of the EMG signals based on hand movements and channel placement, which was followed by the movement of the robot arm.

Skin has a dynamic surface and offers essential information through biological signals originating from internal organs, blood vessels, and muscles. Soft and stretchable bioelectronics can be used in wearable machines for long-term stability and to continuously obtain distinct bio-signals in conjunction with repeated expansion and contraction with physical activities. While monitoring bio-signals, the electrode and skin must be firmly attached for high signal quality. Furthermore, the signal-to-noise ratio (SNR) should be high enough, and accordingly, the ionic conductivity of an adhesive hydrogel needs to be improved. Here, we used a chitosan-alginate-chitosan (CAC) triple hydrogel layer as an interface between the electrodes and the skin to enhance ionic conductivity and skin adhesiveness and to minimize the mechanical mismatch. For development, thermoplastic elastomer Styrene-Ethylene-Butylene-Styrene (SEBS) dissolved in toluene was used as a substrate, and gold nanomembranes were thermally evaporated on SEBS. Subsequently, CAC triple layers were drop-casted onto the gold surface one by one and dried successively. Lastly, to demonstrate the performance of our electrodes, a human electrocardiogram signal was monitored. The electrodes coupled with our CAC triple hydrogel layer showed high SNR with clear PQRST peaks.

The measurement of biosignals in the clinical and healthcare fields is fundamental; however, conventional electrodes pose challenges such as incomplete skin contact and skin-related issues, hindering accurate biosignal measurement. To address these challenges, conductive hydrogels, which are valuable owing to their biocompatibility and flexibility, have been widely developed and explored for electrode applications. In this study, we fabricated a conductive hydrogel by mixing polyethylene glycol diacrylate (PEGDA) with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) polymers dissolved in deionized water, followed by light-triggered crosslinking. Notably, this study pioneered the use of a PEGDA−PEDOT:PSS hydrogel for electrocardiogram (ECG) monitoring- a type of biosignal. The resulting PEGDA−PEDOT:PSS hydrogel demonstrated remarkable conductivity while closely approximating the modulus of skin elasticity. Additionally, it demonstrated biocompatibility and a high signal-to-noise ratio in the waveforms. This study confirmed the exceptional suitability of the PEGDA−PEDOT:PSS hydrogel for accurate biosignal measurements with potential applications in various wearable devices designed for biosignal monitoring.