Chenjie Xu

Effective tissue regeneration requires precise spatiotemporal therapeutic delivery while maintaining scaffold mechanical integrity, which remains a major challenge in regenerative medicine. Here, we present an ultrasound (US)-activated tissue regeneration platform based on engineered osteogenic microbubbles (MMB-BMPs) embedded in a dynamic hyaluronic acid hydrogel (dHA), forming a mechanically robust scaffold (dHAMBH). Upon repeated US stimulation at the resonant frequency, MMB-BMPs underwent stable oscillation within the hydrogel, enabling stepwise, on-demand release of iron oxide nanoparticles (IONPs) and bone morphogenetic protein-2 (BMP-2), while maintaining scaffold integrity after multiple stimulation cycles. This controlled co-delivery enhances osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs). In a mouse critical-sized calvarial defect model, the dHAMBH hydrogel combined with US stimulation accelerated bone regeneration, achieving a 1.7-fold increase in new bone volume compared with the non-US stimulated control. Overall, this work establishes a US-activated platform that enables precise, repeatable therapeutic delivery to enhance tissue regeneration.

Cryomicroneedles offer a route to minimally invasive intradermal delivery of living cells, but their cryogenic formulations must reconcile cell protection with toxicity and device-fabrication constraints. Here we report an AI-assisted workflow for viability-focused cryoprotectant screening in cryomicroneedle development, combining literature curation, Gaussian-process surrogate modelling, Bayesian optimization, and sequential wet-lab validation. A curated dataset of 198 mesenchymal stem-cell cryopreservation formulations from 52 contributing sources was converted into 21 ingredient features and used to train an uncertainty-aware literature prior. Although this model captured structure in the literature data, it failed on the first prospective wet-lab batch, motivating iterative correction with assay-specific results. Across ten validation stages and 106 wet-lab observations, batch RMSE decreased from 41.21 to 6.86 percentage points, and rank correlations were consistently positive in later batches. The highest single-run observation reached 95.15% post-thaw membrane viability with low DMSO, ectoin, ethylene glycol, and fetal bovine serum. High viability did not ensure intact cryomicroneedle formation, establishing multi-objective optimization as the next development stage. These results demonstrate a practical, data-efficient workflow for screening cryoprotectants while positioning viability optimization as one component of cryomicroneedle formulation development. Project code is available at https://github.com/baitmeister/ML-for-CryoMN.

Psoriasis, a chronic inflammatory skin disease, presents treatment challenges including systemic side effects and inadequate topical drug delivery. Herein, we developed a hyaluronic acid (HA)-based dissolving microneedle platform delivering tumor necrosis factor-alpha (TNF-α)-targeting small interfering RNA (siRNA) and dexamethasone co-loaded within dual-functional lipid nanoparticles (LNPs). This LNP design innovatively integrates dexamethasone into its lipid structure, combined with siRNA to enhance stability and anti-inflammatory efficacy while minimizing immunogenicity. The HA microneedles enabled localized, minimally invasive delivery of LNPs into psoriatic lesions. Physicochemical characterization confirmed stable co-loading of siRNA and dexamethasone, with dexamethasone enhancing both LNP stability and siRNA protection. In-vitro studies demonstrated a dual-action mechanism: Dexamethasone suppressed inflammatory signaling pathways while siRNA silenced TNF-α expression, leading to superior inhibition of key proinflammatory cytokines. In a psoriasis-like mouse model, this combinatorial strategy significantly reduced disease severity, normalized epidermal hyperplasia, and decreased immune cell infiltration compared to single-agent therapies. The structural incorporation of dexamethasone within LNPs represents a critical advancement, enabling localized immunomodulation that mitigates systemic risks while amplifying TNF-α suppression. This integrated approach achieved sustained therapeutic effects with reduced dosing frequency. By co-delivering gene silencing and pharmacological agents via a patient-compliant dissolving microneedle system, our work establishes a precision medicine strategy for psoriasis management, addressing both inflammatory pathways and drug delivery limitations.

The nanoscale organization of cell-adhesive ligands is increasingly recognized as a determinant of cell behavior, yet whether it directly regulates cellular metabolism remains unclear. Here we show that supramolecular clustering of integrin-binding ligands regulates mitochondrial respiratory capacity through integrin-mediated mechanotransduction. Supramolecular ligand clustering induces integrin redistribution and cytoskeletal remodeling, leading to mitochondrial reorganization and a selective constraint on oxidative phosphorylation. This respiratory limitation functionally constrains tumor cell migration and invasion and cannot be overcome by restoring cytoskeletal contractility, whereas replenishing mitochondrial metabolic substrates effectively rescues motility. In a HeLa xenograft model, the integrin-binding supramolecular system suppresses tumor growth and reduces extracellular matrix deposition. These findings identify mitochondrial respiratory capacity as a critical downstream effector of integrin mechanosignaling and establish extracellular ligand organization as a previously unrecognized driver of mechanically encoded metabolic regulation.

Engineering extracellular microenvironments to control stem cell fate remains a central challenge in regenerative medicine. Here, we develop ECM-mimetic cellular patches formed by the supramolecular assembly of laminin-derived, integrin-binding ligands. The resulting fibrillar networks exhibit well-defined molecular packing and nanoscale ligand distribution, enabling specific engagement of apical integrin β1 on mesenchymal stem cells. This controlled interface converts molecular assembly into hierarchical mechanotransduction, coordinating cytoskeletal remodeling, nuclear deformation, and chromatin reorganization to drive neuronal reprogramming without genetic or chemical induction. Mechanistic studies reveal that the interplay between ligand assembly, spatial orientation, and network stability governs integrin activation and downstream transcriptional regulation. These findings demonstrate how molecularly programmed assemblies can transform passive matrices into active, cell-instructive materials. This work establishes a framework for designing supramolecular systems that couple structural hierarchy with mechanotransductive control to direct stem cell fate and advance regenerative material strategies.

A porous microneedle-integrated electrochemical aptamer sensor allows for the rapid tear extraction and quantitative biomarker detection in a single device for dry eye disease.

This article introduces the development of Nanoflare (NF) nanosensors for detecting and monitoring cellular insulin mRNA in the culturing of beta cells and islets. These probes are designed using the classic spherical nucleic acid (SNA) technology, consisting of densely packed and highly oriented oligonucleotide sequences on gold nanoparticles. Each oligonucleotide is hybridized to a flare strand bearing a distinct fluorophore label, with all sequences complementary to the target strand. We designed the recognition strand targeting insulin mRNA ( Ins2 , the ortholog of the human insulin gene). When the target strand is introduced, the fluorescence intensity of the In2‐NF solution increases more than 24‐fold. A linear correlation was observed between the fluorescence signal and the concentration of the target strand in the range of 0.01–0.1 µ m (R ² = 0.9997). Finally, the In2‐NF sensors were applied to monitor the cellular expression of insulin mRNA in MIN6 cells (2D culture), MIN6 cell spheroids (3D culture), and rat islets. In the MIN6 cell experiment, NF signals were also correlated with qPCR results. All the results suggest that SNA‐based In2‐NFs are capable of optical detection of intracellular insulin mRNA.

Conventional robotic systems exhibit limited mobility in media characterized by substantial resistance, e.g., solid-liquid mixture (SLM) and solid granular medium (SGM). This challenge is particularly pronounced for untethered miniature robots, as they often lack the capacities to generate sufficient force outputs or to implement strategies that reduce resistance from the surrounding medium. Here, we propose an impact-driven magnetic untethered miniature robot (RoboIMP) capable of delivering repeatable high-force outputs of up to 3 N, surpassing the theoretical force limits of conventional magnetic robots at the same characteristic length. RoboIMP uses reciprocal oscillation to fluidize the surrounding medium, thereby reducing the resistance from the medium by up to 13-fold. This enables effective locomotion of an untethered miniature robot in both SLM and SGM. By integrating functional modules, the proposed system demonstrates various applications, including pipeline cleaning, cargo delivery and retrieval, and navigation in the presence of chyme.

The integration of microneedles (MNs) with microfluidics, microelectronics, or artificial intelligence is applied to MN-based sampling devices, biosensors and electrodes, enabling intelligent health monitoring and personalized disease management.

Subcutaneous implantation is favored for its accessibility and safety, making it a valuable site for cell transplantation. However, the relatively poor vascularization of the subcutaneous space hinders the implant's integration...