Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes from adipose-derived stem cells (ADSC-EXOs) promote diabetic wound healing through the modulation of oxidative stress. We found that ADSC-EXOs could promote proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, and endothelial cells. Furthermore, ADSC-EXOs reduced the reactive oxygen species (ROS) levels in these cells and protected them against hypoxic and oxidative stress damage. Finally, the local injection of ADSC-EXOs at wound sites significantly increased collagen deposition and neovascularization while reducing ROS levels and cell death; thus, it led to accelerated diabetic wound closure. The mechanism underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on the cell surface; these functions could be inhibited by an anti-HSP90 antibody. Exosomal HSP90 could bind to the low-density lipoprotein receptor-related protein 1 (LRP1) receptor on the recipient cell membrane, leading to activation of the downstream AKT signaling pathway. Knockdown of LRP1 and inhibition of the AKT signaling pathway by LY294002 in fibroblasts was sufficient to impair the beneficial effect of ADSC-EXOs. In summary, ADSC-EXOs significantly accelerated diabetic wound closure through an exosomal HSP90/LRP1/AKT signaling pathway.

Severe soft tissue defects and amputated digits are clinically common injuries. Primary treatments include surgical free flap transfer and digit replantation, but these can fail because of vascular compromise. Postoperative monitoring is therefore crucial for timely detection of vessel obstruction and survival of replanted digits and free flaps. However, current postoperative clinical monitoring methods are labor intensive and highly dependent on the experience of nurses and surgeons. Here, we developed on-skin biosensors for noninvasive and wireless postoperative monitoring based on pulse oximetry. The on-skin biosensor was made of polydimethylsiloxane with gradient cross-linking to create a self-adhesive and mechanically robust substrate that interfaces with skin. The substrate was shown to exhibit appropriate adhesion on one side for both high-fidelity measurements of the sensor and low risk of peeling injury to delicate tissues. The other side demonstrated mechanical integrity to facilitate flexible hybrid integration of the sensor. Validation studies using a model of vascular obstruction in rats demonstrated the effectiveness of the sensor in vivo. Clinical studies indicated that the on-skin biosensor was accurate and more responsive than current clinical monitoring methods in identifying microvascular conditions. Comparisons with existing monitoring techniques, including laser Doppler flowmetry and micro-lightguide spectrophotometry, further verified the sensor’s accuracy and ability to identify both arterial and venous insufficiency. These findings suggest that this on-skin biosensor may improve postoperative outcomes in free flap and replanted digit surgeries by providing sensitive and unbiased data directly from the surgical site that can be remotely monitored.

Achieving accurate locating of perforating arteries (PAs) has great clinical value in various biomedical applications, such as free flap transfer. However, the anatomical variability of these arteries presents a major challenge in PA locating, and existing methods have various disadvantages, limiting their applications. Here, we propose a reusable and flexible hydrogel biosensor array for noninvasive, precise, and efficient PA locating. Particularly, we develop electrically responsive hydrogels to establish rapidly detachable device/hydrogel interfaces, endowing the reusability of the biosensor array. Meanwhile, the adhesion of hydrogel/skin interfaces is also enhanced to facilitate high-fidelity signal acquisition. By analyzing the photoplethysmography (PPG) infrared (IR) signals, the biosensor array can accurately and responsively locate PAs across different types of free flaps in clinical cases, outperforming existing techniques. This biosensor array represents a promising platform for PA locating. The strategy of hydrogel interface design paves the way for the development of reusable flexible electronics in biomedical applications to avoid cross-infection and reduce device costs.

Flexible electronics for healthcare applications have been drawing significant attention and show great promise for monitoring blood circulation (e.g. postoperative monitoring of free flaps). However, existing methods for design and fabrication of interfaces with human skin still cannot meet the challenging clinical requirements of superior adhesion during monitoring, and avoiding wound damage during peel-off. Here, we propose a soft biosensor with universal responsive hydrogel interfaces for detecting blood circulation complications. Particularly, we develop thermoresponsive and printable hydrogel inks to rapidly achieve high-precision patterning and wide-range adhesion regulation of interface layers. In clinical cases, the hydrogel biosensor can establish robust hydrogel/flap skin coupling for high-fidelity signal acquisition during monitoring, and ensure benign detachment to prevent tissue injury after monitoring. We achieve precise arterial perfusion monitoring based on the perfusion index (PI) via an 810 nm light source. Additionally, we propose a new metric, the balance index (BI), to monitor venous congestion. By analyzing BI, PI and skin temperature, the biosensor enables accurate detection and differentiation of blood circulation complications. The printable thermoresponsive hydrogel can be adopted as a universal interface in flexible electronics for healthcare applications, and the biosensor represents a promising platform for blood circulation monitoring.

Neurological disorders severely impair the daily life of patients, necessitating precise assessments of neural conduction pathway damage to guide effective diagnosis and treatment. However, current clinical neurodiagnostic equipment is expensive, bulky, and restricted to hospital settings. Furthermore, the rigid nature and low adhesion of conventional electrodes lead to the acquisition of low‐quality neurophysiological signals. Here, we develop a soft hybrid electronic system assembled with printed responsive hydrogel electrodes. By synthesizing thermoresponsive hydrogel microsphere inks, we achieve rapid direct‐printed patterning of interface layers. Based on a thermally triggered hydration‐dehydration strategy of hydrogel microspheres, the hydrogel electrodes demonstrate customizable adhesion, enabling intimate integration with skin for high‐fidelity signal acquisition and gentle detachment after monitoring. Through hydrogel interface modification, on‐skin electrodes also show excellent charge injection capability for stimulation and improved signal‐to‐noise ratio (SNR). The integration of hydrogel patches with the hybrid electronic system enables high‐frequency and high‐fidelity acquisition of subtle neural conduction signals. We further apply this system to assess injuries to the median and ulnar nerves in clinical cases, realizing accurate diagnosis of neural impairment while ensuring customized adhesion regulation. This user‐friendly system holds great promise as a low‐cost and portable diagnostic platform for telemedicine, home‐based care, and clinical settings.