Electrically controlled hyaluronic acid-based hydrogel for sustained and repeatable metronomic chemotherapy.

Photoresponsive and UCST-Type thermoresponsive block Copolymer-Based composite micelles for Dual-Stimuli-Triggered selective and programmable release

Perspectives and trends in gas delivery systems based on ultrasound responsive nanomaterials for cancer therapy.

Cellulose nanofibrils-based emulgels: Impact on surface film formation and performance as slow-release fertilizers.

Three-dimensional (3D) bioprinting has emerged as a transformative technology for drug delivery that offers anatomically customized, spatially controlled, and programmable release systems. These innovations hold significant promise in the fields of anesthesiology and pain medicine, particularly for postoperative pain control, where precise, localized, and sustained analgesic effects are desirable. This review highlights the current applications and future directions of 3D bioprinting for the delivery of local anesthetics, anti-inflammatory agents, and neuromodulators. By incorporating patient-specific designs and spatiotemporal release strategies, 3D-printed drug delivery systems can reduce systemic drug exposure, enhance tissue recovery, and improve analgesic efficacy. Despite these advantages, several challenges remain, including issues related to regulatory classification, manufacturing reproducibility, scalability, and long-term biocompatibility. As research advances and interdisciplinary collaboration improves, 3D bioprinting is poised to become an integral tool for personalized and procedure-specific pain management in the perioperative setting.

Stepwise exfoliated microneedle patch for immediate and concomitant targeted booster vaccination.

Theranostic systems that integrate diagnostic monitoring and therapeutic intervention within unified platforms represent a transformative approach for precision medicine. While wearable microneedle (MN)‐based devices offer an ideal form factor for such systems, their development has been constrained by limitations in molecular recognition specificity, intelligent decision‐making capability, and controlled drug release precision. Nucleic acid technology emerges as a comprehensive solution to these challenges, leveraging its inherent programmability and molecular recognition versatility to address all three core theranostic components. This review systematically examines recent advances in nucleic acid‐based strategies for intelligent theranostics, focusing on three fundamental modules: (1) in situ monitoring systems employing aptamers, CRISPR mechanisms, and molecular pendulums; (2) decision‐making units utilizing threshold‐controlled circuits and feedback‐regulation networks; and (3) stimulus‐responsive drug delivery units featuring programmable release mechanisms for various therapeutic agents. We further highlight integrated nucleic acid‐MN platforms that demonstrate closed‐loop operation, continuously sensing biomarker fluctuations and triggering precise therapeutic responses. Finally, we discuss prevailing challenges in stability, specificity, and clinical translation, while outlining future research directions aimed at advancing autonomous molecular decision systems for personalized medicine applications. This comprehensive analysis provides foundational insights for developing next‐generation intelligent theranostic platforms capable of adaptive, precision healthcare delivery.

Microneedles (MNs) provide a minimally invasive and efficient platform for transdermal drug delivery, offering precise control over dosage and release kinetics. Recent advances in dual-drug delivery using dissolvable MNs have focused on optimizing structural design, material composition, and programmable release mechanisms. Dual-layer or core-shell MN configurations allow spatial and temporal separation of drugs, while stimuli-responsive polymers enable release in response to physiological cues such as glucose concentration, pH, or reactive oxygen species (ROS). This review summarizes emerging strategies for co-delivery through dissolving MNs, emphasizing how design parameters including morphology, materials, and nanoformulations influence mechanical performance and drug-release profiles. Applications in cancer, diabetes, wound healing, and inflammatory diseases are highlighted. For example, a dual-drug MN co-loaded with an anti-PD-L1 antibody and 1-methyl-D,L-tryptophan (1-MT) achieved prolonged intratumoral retention and enhanced antitumor efficacy. Similarly, MNs incorporating MnSH nanozymes and polymyxin B demonstrated synergistic antibacterial and pro-angiogenic effects in wound models. The integration of nanocarriers and responsive polymers has expanded the therapeutic potential of MN-based systems, enabling precise, localized, and sustained co-delivery of active agents. Finally, current challenges including large-scale manufacturing, reproducibility, clinical validation, and regulatory approval are discussed to outline future directions for translating MN-based dual-drug delivery into clinical practice.

Extracellular vesicles (EVs), as natural mediators of intercellular communication, hold substantial promise for diagnostics, drug delivery, and regenerative medicine. However, their translation remains constrained by vulnerability to hostile microenvironments, rapid clearance with a short in vivo half-life, and limited control over localization and dosing. Encapsulation based on multi-scale materials engineering can endow EVs with programmable release, environmental responsiveness, and site-specific delivery. In this review, recent advances in EV encapsulation technologies are synthesized. Guided by structural design principles, encapsulation is classified into three scales comprising nanoscale, microscale, and macroscale, and each scale provides distinct mechanisms for protection and controlled release. A comparative overview of representative strategies is then offered, and their advantages and application contexts are summarized. Finally, key challenges and future directions are outlined, including elucidation of material-EV interactions, development of scalable and standardized manufacturing, and realization of on-demand, spatiotemporally precise release in response to physiological cues.

Acylsilanes representa unique class of organosilicon compoundswith distinctive photochemical reactivities, including hydrogen atomtransfer (HAT) and silyl shift pathways. Recently, a new photolabileprotecting group (PPG) benzoyldiisopropylsilane (BDIPS) featuringan acylsilane functionality was introduced for alcohol protection.While the photomediated deprotection of aliphatic silyl ethers inmethanol provided the free alcohols, BDIPS-protected benzyl or allylalcohols resulted in rearranged ketones upon photoexcitation in acetonitrile.In this work, we systematically investigate the photochemical behaviorof different BDIPS-ethers, focusing on the mechanistic divergenceleading to either alcohol release as PPG or rearranging ketone formation.Through a combined approach of femtosecond transient absorption spectroscopyand density functional theory calculations, we elucidate the competingreaction pathways for model compounds 1a, 1b, and 1c. Our results reveal that the presence of anα-hydrogen adjacent to an olefinic moiety kinetically favorsthe HAT pathway, yielding rearranged ketone products, while its absencepromotes a silyl shift mechanism that results in efficient alcoholphotodeprotection. Furthermore, solvent-dependent studies demonstratedistinct photoreaction behaviors for 1c in methanol andacetonitrile, underscoring the role of the local chemical environmentin steering reaction outcomes. This study provides fundamental insightsinto the structure–reactivity relationships of acylsilane-basedPPGs and offers a strategic basis for the rational design of photoresponsivesystems with programmable release properties.

Encapsulation of fish oil within oleogels can potentially prevent oxidation and enable its use in food with programmable release within the gastrointestinal tract. Here, we report on the formation of oleogels from two different fish oils—salmon oil (SO) and cod liver oil (CLO)—using different concentrations of either rice bran wax (RBW) or myristic acid (MA) as gelators. The gels were assessed with respect to their structural, thermal, viscosity, digestive, and oxidative properties. Polarized light microscopy (POM) revealed that RBW consistently produced dense, interconnected crystalline networks across both oils, while MA formed larger, spherulitic crystals that were more sensitive to the oil type. This was further supported by time-lapse imaging, showing faster crystal growth of MA in cod liver oil. Viscosity studies indicate that the molecular weight and concentration of gelator, as well as the type of fish oil (SO vs. CLO), significantly impact the shear stability of the oleogels. Thermal and viscosity analyses confirmed that RBW-based oleogels exhibited higher crystallization temperatures and stronger viscoelastic behaviour. Based on oxidative stability measurements—as measured by peroxide value (PV) analysis—encapsulation within oleogels does not lead to significant oxidation of the fish oils and also attenuates further oxidation upon storage. The fish oil oleogels were stable when exposed to either simulated gastric or intestinal fluids (SGF and SIF, respectively), but decomposed after sequential exposure first to SGF and then to SIF. These findings could broaden the range of food products which can be fortified with fish oils.

Thermoresponsive hydrogel microcapsules have received considerable attention as controlled release systems due to their tunable molecular permeability. However, conventional microcapsules based on swelling/deswelling transition often suffer from poor mechanical properties as well as limited range of molecular cut‐off tunability, restricting their practical use. In this work, thermal phase separation in hydrogel microcapsules is introduced to achieve mechanical toughening as well as broad range of control over molecular permeability. By using poly(acrylic acid) (PAAc) hydrogels ionically crosslinked with calcium/acetate ions as the microcapsule shell, a polymer dense state can be induced upon heating above the transition temperature. Compression tests and dye permeation studies demonstrate a significant increase in modulus as well as substantial reduction in molecular cut‐off threshold upon phase separation. Moreover, it is demonstrated that the release profile of the encapsulated substances can be programmed by adjusting the duration of thermal exposure, which governs the recovery kinetics of the hydrogel network. The showcased phase separation‐induced strategy enables unprecedented control of the molecular permeability and significant enhancement in mechanical properties of the hydrogel microcapsules, offering a new avenue in the design of advanced stimuli‐responsive microcapsules.

The technology and ability of 3D printing have transformed the sphere of personalized medicine, allowing manufacturing of the customized drug delivery to address diverse needs of a specific patient with regard to physiologic, pharmacokinetically, and therapeutically oriented preferences. This review generates a pharmaceutics-oriented view of the use of novel 3D printing technologies such as the Fused Deposition Modeling (FDM), Stereolithography (SLA), and inkjet printing in the development of personalized dosage forms comprising of oral tablets, implants, microneedles, and transdermal patches. Animal model experimental preclinical research, such as that in rabbits, rats, and mice, has proven the capability of the technologies to perform zero order release and controlled release of drugs, the capability to release multiple drugs using staggered kinetics, and to provide site-specific or minimally invasive delivery. The results support the benefits of structural flexibility, programmable release profiles, and improved patient adherence, especially in the case of complex conditions and important vulnerable groups of patients (pediatric and geriatric). But there are still some impediments on the way to clinical application, such as thermal instability of labile drugs, biocompatibility issues, poor reproducibility in device operation, a lack of standard regulatory frameworks, and insufficient long-term safety documentation. The review ends with a purpose of identifying the future research and development directions that include the necessity of the use of superior biocompatible materials, inherent hybrid printing methods and scalability in production, as well as interdisciplinary cooperation to enable clinical translation and redefine the future of personalized drug treatment.

ABSTRACTLinear–bottlebrush (LB) amphiphilic block copolymers offer a unique platform for designing self‐assembled nanostructures with tunable responsiveness. In this study, we synthesized a series of LB copolymers incorporating oxidation‐sensitive thioether groups in the hydrophobic bottlebrush segment, while systematically varying the brush side chain length under fixed backbone length and graft density. Self‐assembly in aqueous media led to spherical particles with distinct internal morphologies, including vesicular and densely packed structures, depending on brush architecture. Disassembly triggered by hydrogen peroxide revealed that shorter‐brush LBs with internally hollow structures disassembled more rapidly, whereas longer‐brush LBs exhibited slower disassembly due to densely packed cores and limited accessibility of oxidants. These results demonstrate that the internal morphology and oxidative responsiveness of LB assemblies can be finely tuned through architectural control, providing valuable design principles for developing stimuli‐responsive nanocarriers with programmable release profiles.

Programmable hierarchical hydrogel dressing for sequential release of growth factor and DNase to accelerate diabetic wound healing.

Double network microgels based on dextran and fibrin with tunable structural, mechanical, and degradation properties.

Reinnervation is of great significance for bone regeneration and remodeling. Although great progress has been made in bone tissue engineering, reconstruction of neural networks is still a challenge and leads to limited osteogenesis. Nerve growth factor (NGF) guides the innervation in the early stage of bone healing, and bone morphogenetic proteins (BMPs) are continuously expressed during the bone healing process that can induce osteogenic differentiation. A microsphere-hydrogel scaffold mimicking the dynamic performance of NGF and BMPs in a timely manner is designed and constructed via 3D printing. The scaffold enables rapid release of NGF mimetic peptide and long-lasting sustained release of BMP-2 mimetic peptide, which aims at restoring innervation. The rapid release of NGF mimetic peptide could significantly promote migration of RSC96 and axon elongation of pheochromocytoma cells in vitro. Meanwhile, co-delivery of NGF/BMP-2 mimetic peptides could synergistically enhance osteogenic differentiation of bone marrow mesenchymal stem cells mediated by calcitonin gene-related peptide (CGRP)-dependent signaling pathway. Moreover, the scaffold accelerates neural network reconstruction and effectively improves new bone regeneration in vivo. In conclusion, this 3D printed microsphere-hydrogel scaffold could simulate the temporal release profile of natural growth factors, and provide a promising strategy for innervated bone regeneration.

Hydrogel-based drug delivery systems hold significant clinical potential by enabling precise spatial and temporal control over therapeutic release, ranging from metabolites, macromolecules to other cellular and subcellular constructs. However, achieving programmable release of payloads with diverse molecular weights at distinct rates typically requires complex polymer designs that can compromise the accessibility and biocompatibility of the delivery system. We present a scalable method for producing injectable, micrometer-scale alginate hydrogel particles (microgels) with precisely tuned microstructures for multiplexed, programmable cargo release. Our approach integrates an established jetting technique with a simple postsynthesis ion-exchange process to fine-tune the cross-linked microstructure of alginate microgels. By varying cation type (Ca2+, Mg2+, Na+) and concentration, we systematically modulate the microgels' chemical and physical properties to control release rates of model compounds, including rhodamine B, methylene blue, and dextrans of various molecular weights. Additionally, a PEG-alginate composite microgel system is used to demonstrate the pre-programmed stepwise release of rhodamine B. These findings offer a straightforward strategy for postsynthetic manipulation of ionic microgels with controllable release performances, paving the way for advanced biomedical applications.

Pickering emulsions have garnered significant attention for their ability to facilitate the controlled and effective delivery of active ingredients across various sectors, including drug release, agriculture, cosmetics, and interfacial catalysis. However, achieving the release of encapsulated active substances typically requires the disruption of emulsion droplets, making programmable release a notable challenge. This study develops a colloidal layer with nanogates at the oil-water interface of Pickering emulsion, utilizing UV light as a non-contact, remote stimulus to enable effective programmable release of encapsulated active substances. By alternating UV and visible light irradiation, this work induces cis-trans isomerization of azobenzene molecules on silica particles, allowing the gaps between colloidal particles to open and close. This demonstrated a promising nanogate effect under UV irradiation, facilitating the programmable release of active substance (perylene) from the Pickering emulsion droplets. This Pickering emulsion system offers precise control over the release amount of perylene by adjusting the colloidal particle size and the duration of UV-visible light exposure, all while maintaining emulsion stability. The successful implementation of this strategy presents a promising platform for non-invasive, programmable release of active substances across diverse applications in food, cosmetics and pharmaceutical fields.

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system exhibits extraordinary capability in the field of molecular diagnosis and biosensing, attributed to its trans-cleavage ability. The precise modulation of performance has emerged as a significant challenge in advancing CRISPR technology to the next stage of development. Herein, we reported a CRISPR/Cas12a regulation strategy based on an overhanging activator. The presence of overhanging domains in activators creates steric hindrances that have a substantial impact on the trans-cleavage activity and activation timing of Cas12a. The trans-cleavage activity of Cas12a can be finely tuned by adjusting the position, length, and complementarity of the overhanging domains. Moreover, specific structures exhibit characteristics of automatic delayed activation. The presence of overhanging domains enables precise and timely activation of Cas12a, facilitating multifunctional applications. This system effectively accomplishes dynamic regulation, programmable release of cargo, logical operations, and multi-enzyme detection. The flexibility and versatility of this simple and powerful CRISPR regulatory strategy will pave the way for expanded applications of CRISPR/Cas in biotechnology, bioengineering, and biomedicine.