Benjamin M. Wu

Wearable microneedle biosensors promise real-time molecular monitoring for precision medicine but are limited by low sensitivity and tissue abrasion. Overcoming these challenges, we recast electrode functionality not merely as a sensing substrate but as a mechanism for resilient, high signal-to-noise ratio (SNR) measurements in tissue. Our microneedle-based resilient nanostructured bioelectrode (RNB) is fabricated using a bilayer process that strengthens the electrode with a micrometer-thick gold adhesion layer and reduces fabrication-induced stress through controlled dealloying. The resulting RNBs are corrosion resistant, stable over a wide potential window, and have an artifact-free, nanocavity-textured interface. They integrate receptor-based electrochemical biosensors with enhanced SNR through increased active area, diffusion, and antifouling while remaining abrasion immune in megapascal-stiff tissues. The RNB extended in vivo biosensor lifetime for pharmacokinetics monitoring to 6 days in a freely moving rat. Paired with a blood–interstitial fluid equilibrium–based bioanalytical framework, the RNB accurately derived blood-equivalent pharmacokinetic parameters, enabling not only precision dosing of narrow therapeutic index drugs but also the direct assessment of hepatic and renal clearance. In hepatic studies, the RNB revealed delayed clearance of a chemotherapeutic (irinotecan) in liver-damaged models. In renal studies, RNB recordings correlated with blood antibiotic pharmacokinetics across chronic kidney disease severities. The RNB detected renal impairment earlier than conventional biomarker thresholds through drug clearance quantification and captured recovery under therapeutic intervention. These results establish the RNB as a viable microneedle platform for high-fidelity in vivo deployment of electrochemical biosensors, enabling minimally invasive, longitudinal monitoring of low-concentration analytes and real-time assessment of organ function.

The orthodontic landscape is currently witnessing a significant technological evolution with the emergence of direct 3D-printed aligners (DPAs), which promise to close the digital workflow loop by eliminating the geometric limitations and solid model waste inherent to traditional thermoformed clear aligners (TCAs). This review provides a comprehensive analysis of the material science governing this transition from inert thermoplastic sheets to reactive photocurable resins. We explore the fundamental chemistry of DPA materials, and the pivotal role of post-processing in ensuring mechanical integrity and biocompatibility. Beyond passive mechanics, this review highlights preclinical research in functional material engineering, detailing how experimental DPAs are being investigated for the integration of antibacterial agents, remineralization fillers, and drug delivery systems. Furthermore, we evaluate the limited but emerging clinical data on DPAs, contrasting their shape-memory properties and force delivery profiles with conventional appliances, while critically addressing emerging safety concerns regarding monomer elution and microplastic generation. We conclude that while DPA technology offers superior dimensional control, comprehensive life cycle assessments and long-term in vivo trials are essential to fully substantiate their clinical efficacy, overall sustainability, and potential as advanced orthodontic appliances.

Multi-target drug design represents a paradigm shift in tackling the complexity and heterogeneity of diseases such as cancer. Conventional single-target therapies frequently face limitations due to network redundancy, pathway compensation, and adaptive resistance mechanisms. In contrast, deep generative models, empowered by advanced artificial intelligence algorithms, provide scalable and versatile platforms for the de novo generation and optimization of small molecules with activity across multiple therapeutic targets. This review provides a comprehensive overview of the recent landscape of AI-driven deep generative modeling for multi-target drug discovery, highlighting breakthroughs in model architectures, molecular representations, and goal-directed optimization strategies. We also examine the emergence of self-improving learning systems, closed-loop frameworks that iteratively refine molecular candidates through integrated feedback, as a transformative approach to adaptive drug design. Finally, key challenges, current limitations, and emerging trends are discussed to guide the evolution of next-generation intelligent and autonomous drug discovery pipelines for multi-target therapeutics.

In recent years, significant advancements in the field of advanced materials and hydrogel engineering have enabled the design and fabrication of smart hydrogels and nanogels that exhibit sensitivity to specific signals or pathological conditions, leading to a wide range of applications in drug delivery and disease treatment. This comprehensive review aims to provide an in-depth analysis of the stimuli-responsive principles exhibited by smart hydrogels in response to various triggers, such as pH levels, temperature fluctuations, light exposure, redox conditions, or the presence of specific biomolecules. The functionality and performance characteristics of these hydrogels are highly influenced by both their constituent components and fabrication processes. Key design principles, their applications in disease treatments, challenges, and future prospects were also discussed. Overall, this review aims to contribute to the current understanding of gel-based drug delivery systems and stimulate further research in this rapidly evolving field.

Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1’s osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).

Following the global spread of COVID-19, scientists and engineers have adapted technologies and developed new tools to aid in the fight against COVID-19. This review discusses various approaches to engineering biomaterials, devices, and therapeutics, especially at micro and nano levels, for the prevention, diagnosis, and treatment of infectious diseases, such as COVID-19, serving as a resource for scientists to identify specific tools that can be applicable for infectious-disease-related research, technology development, and treatment. From the design and production of equipment critical to first responders and patients using three-dimensional (3D) printing technology to point-of-care devices for rapid diagnosis, these technologies and tools have been essential to address current global needs for the prevention and detection of diseases. Moreover, advancements in organ-on-a-chip platforms provide a valuable platform to not only study infections and disease development in humans but also allow for the screening of more effective therapeutics. In addition, vaccines, the repurposing of approved drugs, biomaterials, drug delivery, and cell therapy are promising approaches for the prevention and treatment of infectious diseases. Following a comprehensive review of all these topics, we discuss unsolved problems and future directions.

Background: The Midfacial Skeletal Expander (MSE) produces a greater skeletal effect than its dentoalveolar side effects. The aim of this study was to quantify the stability of the different components of MSE expansion post-orthodontic treatment. Methods: Fourteen subjects (mean age of 20.4 ± 3.5 years) were treated with the MSE. The pre-expansion (T0), post-expansion (T1), and post-treatment (T2) CBCT records were superimposed and compared. The rotational fulcrum of the zygomaticomaxillary complex was identified, and angular measurements were generated to assess changes in the zygomaticomaxillary complex (skeletal expansion), dentoalveolar bone (alveolar bone bending), and maxillary first molars (dental tipping). The stability of all three components after orthodontic treatment was also assessed by comparing changes between T0–T1 and T0–T2. Results: Post-expansion, angular measurements showed that skeletal expansion accounted for 87.50% and 88.56% of total expansion, alveolar bone bending for 7.09% and 5.23%, and dental tipping for 5.41% and 6.21% on the right and left sides, respectively. Post-treatment skeletal expansion relapsed by 11.20% and 13.28% on the right and left sides, respectively. Conclusions: The MSE mainly produces skeletal changes with insignificant and negligible dentoalveolar changes immediately after expansion. In the long term, the majority of skeletal expansion was maintained.

Advancing electronics to interact with tissue necessitates meeting material constraints in electrochemical, electrical, and mechanical domains simultaneously. Clinical bioelectrodes with established electrochemical functionalities are rigid and mechanically mismatched with tissue. Whereas conductive materials with tissue-like softness and stretchability are demonstrated, when applied to electrochemically probe tissue, their performance is distorted by strain and corrosion. We devise a layered architectural composite design that couples strain-induced cracked films with a strain-isolated out-of-plane conductive pathway and in-plane nanowire networks to eliminate strain effects on device electrochemical performance. Accordingly, we developed a library of stretchable, highly conductive, and strain-insensitive bioelectrodes featuring clinically established brittle interfacial materials (iridium-oxide, gold, platinum, and carbon). We paired these bioelectrodes with different electrochemical probing methods (amperometry, voltammetry, and potentiometry) and demonstrated strain-insensitive sensing of multiple biomarkers and in vivo neuromodulation.

Bleaching of vital teeth has become common practice in cosmetic dentistry today. Tooth sensitivity and demineralization of the enamel are, however, common side effects associated with hydrogen and carbamide peroxide bleaching. This study investigated if calcium phosphate microspheres, which have remineralizing properties, could be used as an additive without hindering the diffusion of the bleaching agent and if the spheres could be used as a carrier for carbamide peroxide. A remineralizing agent could increase the safety of bleaching and decrease the severity of its side effects. Comparisons between current hydrogen peroxide diffusion studies and previously published work are difficult since many studies include challenging-to-replicate conditions or lack reporting of important parameters. Hence, a diffusion model was designed by Wu Lab (School of Dentistry, University of California, Los Angeles) to measure the diffusion flux and determine the diffusivity of hydrogen peroxide. Physical parameters (e.g., diffusivity) could then be used for direct comparison to the results obtained by future studies. Three whitening gels with increasing amounts of spheres were formulated and tested with 2 commercially available whitening gels. The flux of hydrogen peroxide through 1-mm discs of bovine enamel was measured at steady-state conditions, and the diffusivity was calculated. The results showed that the spheres could be used as a carrier for carbamide peroxide and that the amount of spheres did not affect the diffusivity of peroxide through the enamel discs. Hence, the microspheres are considered promising as an additive to minimize side effects in bleaching gel formulation.