Chenguang Zhang

Stress-related endocrine responses are critical for understanding human performance and mental health. Conventional assessments rely heavily on subjective self-report questionnaires or invasive sampling such as venipuncture. Tears offer a noninvasive source of neurochemical biomarkers, including serotonin, a key regulator of stress and mood. However, real-time and continuous monitoring of tear serotonin has not yet been fully realized. Here, we present a reversible lab-on-a–contact lens platform that integrates a printable, stretchable ferrocene-based electrochemical sensor for in situ detection of serotonin in tear fluid. The device is fabricated on a soft hydrogel lens and uses an electrochemically refreshable redox surface to restore baseline between measurements. Calibration in artificial tears established a limit of detection of 72 picomolar and a dynamic range of 0.1 to 500 nanomolar. Function was maintained for more than 28 days in a tear-like environment and under repeated mechanical deformations (flipping, folding, stretching, and twisting), with stability confirmed by periodic redox cycling. Ocular safety and biocompatibility were demonstrated in a porcine eye model. In a chronic stress mouse model, tear serotonin concentrations inversely correlated with cortisol in both serum and tears, and a first-in-human pilot study further supported the relationship between tear serotonin and stress with off-line analysis by the lab-on-a–contact lens platform. This platform could enable applications in decentralized, noninvasive endocrine monitoring and holds promise as a clinically translatable tool for real-time mental health biomarker assessment.

Infected bone defects present a major clinical challenge, requiring precise sequential therapy that transitions from antibacterial activity to bone regeneration. Piezoelectric materials can transduce external stimulation into bioelectrical cues, providing a promising controllable handle to regulate antibacterial and osteogenic processes. However, conventional piezoelectric scaffolds often lack the capacity to distinctly separate these multifunctional roles, making it difficult to meet the therapeutic needs of different stages in the treatment of infected bone defects. Here, we develop a programmable NIR-responsive periosteum scaffold featuring a Janus bilayer architecture, in which a PDA-rich photothermal side and a non-photothermal piezoelectric side enable spatially separated antibacterial and osteogenic functions. This system integrates a thermoresponsive hydrogel with a piezoelectric polyvinylidene fluoride/barium titanate (PVDF/BT) electrospun membrane, achieving three switchable functional modes: continuous NIR irradiation for antibacterial therapy, intermittent irradiation for immunomodulation, and no irradiation for mechanical support and Ca²⁺ release to facilitate mineralization. In vitro studies demonstrated effective antibacterial efficacy and enhanced pro-healing M2 macrophage polarization, while comprehensive in vivo studies in rat models of 8 mm infected bone defect models achieved over 60% bone healing rate through programmable sequential therapy at 4 weeks. This programmable multi-mode periosteum scaffold provides a promising strategy for temporally orchestrating complex microenvironments, advancing the regenerative medicine for infected bone repair.

Glaucoma remains a leading cause of irreversible blindness worldwide, yet conventional topical therapies are often hampered by poor patient adherence, and standard in-office applanation tonometry captures only static measurements, failing to capture the dynamic nature of intraocular pressure (IOP). Smart contact lenses have emerged as promising tools for home-based, real-time IOP monitoring and feedback-guided therapy; however, most rely on bulky or rigid electronics that impair comfort, safety, and visual performance. Here, we report a battery-free, all-polymer microfluidic theranostic smart contact lens (AP-TSCL) that enables autonomous IOP-responsive glaucoma therapy without bulky electronic components. The AP-TSCL integrates a noninvasive microfluidic IOP sensor with a multistage, pressure-gated drug delivery architecture. Embedded microchannels define distinct activation thresholds, enabling lens deformation under elevated IOP to drive staged release from multiple drug reservoirs. Across in vitro (artificial eye model), ex vivo (enucleated bovine eyes), and in vivo (rabbit ocular hypertension) studies, the device achieved tonometry-aligned IOP tracking, pressure-triggered delivery of timolol or brimonidine above preset thresholds, and IOP lowering comparable to conventional topical therapy. This preclinical evidence suggests that the fully integrated platform may overcome key limitations of existing technologies and offers a clinically translatable solution for personalized ocular care.

The utilization of bioresorbable synthetic bone substitutes with immunomodulatory properties has gained significant attention in dental clinical applications for the absorption of alveolar bone induced by orthodontic treatment. In this study, we developed two distinct materials: a conventional hydroxyapatite (HA) bone powder comprised of hydroxyapatite particles and nanoHA embedded within a poly(caprolactone-co-lactide) (PCLLA) elastomeric matrix. We assessed the physicochemical characteristics of the bone substitute, specifically focusing on its composition and the controlled release of ions. Our findings show that PCLLA-nanoHA has deformable properties under 40 N, and a significant release of Ca and P elements was noted after 7 days in aqueous settings. Moreover, at the protein and gene expression levels, PCLLA-nanoHA enhances the capacity of macrophages to polarize towards an M2 phenotype in vitro. In vivo, PCLLA-nanoHA exhibits comparable effects to standard HA bone powder in terms of promoting alveolar bone regeneration. Extensive investigations reveal that PCLLA-nanoHA surpasses the commonly employed HA bone powder in stimulating bone tissue repair in diabetic mice. We have identified that PCLLA-nanoHA regulates macrophage M2 polarization by activating the PI3K/AKT and peroxisome proliferator-activated receptor gamma (PPAR) signaling pathways, thereby facilitating a favorable local immune microenvironment conducive to bone repair and regeneration. Our findings suggest that PCLLA-nanoHA presents itself as a promising bioresorbable bone substitute with properties that promote macrophage M2 polarization, particularly in the context of regulating the local microenvironment of alveolar bone in diabetic mice, potentially facilitating bone tissue regeneration.