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[Frontier research on smart delivery biomaterials in the field of oral tissue engineering].

Oral tissue repair faces challenges, including complex types of defects, a harsh local microenvironment, and limitations of conventional therapies. Common diseases, such as periodontitis, maxillofacial tumors, trauma, and congenital deformities, cause defects in the alveolar bone and periodontal tissues, affecting a large population. The demand for tissue repair is increasing with accelerating population aging. Defect sites often exhibit a complex microenvironment accompanied with infection, inflammation, ischemia, and immune imbalance, severely impairing the viability and regene-ration of ste

T-cell exhaustion and senescence in cancer: Regulatory circuits and therapeutic state engineering.

In cancer, T-cell state strongly influences antitumor immunity and response to immunotherapy. High-parameter cytometry, single-cell transcri … stimulation, metabolic interventions, epigenetic modulation, immune-checkpoint blockade, and genome engineering onto the state transitions they are intended to influence. This framework separates clinically established approaches from exploratory strategies and provides a testable basis for state-informed biomarker development and therapeutic design.

Engineering a medical device for intranasal immunisation: ensuring targeted delivery and formulation stability.

INTRODUCTION: The efficacy of nasal vaccination critically depends on the delivery method, which must ensure precise and reproducible deposition of the vaccine within the nasal cavity to effectively stimulate mucosal immune structures such as the nasal\x{2011}associated lymphoid tissue (NALT). Transitioning from pre\x{2011}clinical models to human applications is challenging because of anatomical and physiological differences in nasal structure and airflow dynamics. METHODS: We developed a nasal\x{2011}spray device specifically designed for human nasal immunization. The device delivers a broa

Human Factors and Device Engineering in OTC Intranasal Drug Delivery: GentleMist Technology™.

Intranasal drug delivery is noninvasive, rapid-acting, and well suited to self-administration, yet the real-world performance of nasal sprays depends on the interaction among formulation, device mechanics, nasal anatomy, and user technique rather than on the active ingredient alone. This narrative review examines how aerosol science, regional targeting, and human factors jointly shape intranasal performance, using GentleMist Technology™ as a representative example of emerging device-centered development. Computational fluid dynamics (CFD) and anatomically informed in vitro models indicate that

Fibrous Biomaterial Scaffold for Tympanic Membrane Repair: Microarchitectural Engineering and Structure Function Performance.

Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted cons

Инженерный антитела TACI × CD3 для перенаправления Т клеток на множественные миэломы.

Вышеупомянутые аббревиатуры, предназначенные для антигена созревания клеток В (BCMA), являющегося членом сверхсемейства суперрецептора некроза опухоли (TNFR), продемонстрировали замечательную клиническую эффективность в лечении рецидива/рефрактора множественной миеломы (MM). Вместе с тем одной из серьезных проблем является частое снижение регулирования или потеря выражения БКМА у пациентов, получающих иммунотерапию, ориентированную на БКМА, что существенно снижает терапевтическую эффективность и способствует прогрессированию и устойчивости к заболеваниям после первоначальной позитивной реакции

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… Here, we engineered a TACI × CD3 bsAb that redirects T cells to target MM cells. This bsAbs induces robust T-cell activation, proliferation, and potent cytotoxicity against MM cells. … Engineering a TACI-targeted T-cell–redirecting TACI × CD3 bsAb To address resistance in MM cells with reduced BCMA, we searched for alternative targets by reanalyzing Human Protein Atlas data ( https://www.proteinatlas.org ). …

Omics-guided engineering of CHO cells reveals host targets to support AAV production.

The scalable production of recombinant adeno-associated viruses (rAAVs) remains a critical challenge in gene therapy manufacturing. While HEK293 and insect cell systems dominate current production platforms, each presents significant limitations in cost, scalability, and product quality. Chinese hamster ovary (CHO) cells represent an attractive alternative given their established use in biopharmaceutical manufacturing, yet their inability to efficiently support rAAV assembly has hindered development of CHO-based rAAV bioprocesses. Here, we investigate the molecular basis of this limitation by

Application of the CPER reverse genetics system for genetic engineering of rabies virus.

Reverse genetics (RG) systems are essential tools for basic virological studies and applied studies using engineered recombinant viruses in … se-free cloning strategy for conventional RG. Our work establishes CPER as a versatile platform for engineering recombinant RABVs, facilitating rapid generation and genetic manipulation of RABV with potential applications for research on other mononegaviruses.IMPORTANCEReverse genetics systems allow researchers to generate recombinant viruses with precise gen …

Genetic engineering of Staphylococcus haemolyticus: overcoming restriction-modification barriers and targeting virulence genes.

Staphylococcus haemolyticus is an emerging multidrug-resistant nosocomial pathogen noted for robust biofilm formation and complex restriction-modification (RM) systems that hinder genetic manipulation. These barriers have severely limited mechanistic studies into its pathogenesis and immune evasion. Here, we report the development of a molecular toolbox that enables precise genomic engineering of clinical S. haemolyticus isolates. Using PacBio Single-Molecule Real-Time and bisulfite sequencing, we defined the complete genomes and methylomes of nine isolates, generating a functional readout of …

Engineering controlled antimicrobial delivery across biofilm matrix barriers: mechanics, transport and nanocarrier design.

Bacterial biofilms are a major challenge for antimicrobial therapy because they function not only as structured microbial communities, but also as complex biological barriers to drug delivery. Biofilm-associated bacteria are embedded within an extracellular polymeric substance (EPS) matrix that provides mechanical stability, regulates antimicrobial transport and generates heterogeneous microenvironments characterised by nutrient limitation, oxygen gradients and metabolically diverse bacterial subpopulations. As a result, therapeutic failure in mature biofilms often reflects a mismatch between

Diagnostic-Mediated Interactive Superlattices Engineering for Threshold-Saltatory Visual Assessment of Tuberculous Meningitis.

Nonlinear dynamic monitoring is crucial for assessing l-tryptophan (l-Trp) dysregulation progression in tuberculous meningitis (TBM); yet remains challenging due to conventional sensing probes' inherent nondirectionality and poor interfacial response control. Herein, we present a programmable organic-ligand-based self-assembly strategy to construct superlattice nanoprobes with structurally responsive, tunable interfaces. Precisely regulating ligand assembly integrates atomically dispersed platinum layers with organic ligand bilayers, forming an interactive nanobiosensing interface for real-tim

Engineering a versatile Aspergillus niger platform for efficient and scalable biosynthesis of polyketides.

Polyketides are a diverse class of natural products with broad pharmacological activities and substantial industrial relevance; however, their scalable biosynthesis is often constrained by inefficient heterologous expression platforms. In this study, a systematic evaluation of multiple microbial hosts identified Aspergillus niger HL-1 as an efficient fungal chassis for polyketide production. Subcellular compartmentalization analysis revealed that cytosolic biosynthesis significantly outperformed peroxisomal localization, leading to a 5.88-fold increase in triacetic acid lactone (TAL) productio

A Protocol for Engineering Collagen Type II Bioscaffolds to Support Stem Cell Chondrogenesis.

Matrix-based bioscaffolds are crucial tools to advance stem cell-based cartilage regeneration approaches. Collagen type II is one of the major extracellular matrix (ECM) components of hyaline cartilage, thus providing a favorable microenvironment for promoting chondrogenic differentiation. This chapter describes a standardized molecular biology protocol to develop collagen type II bioscaffolds in order to enhance the potential of mesenchymal stem cell (MSC) chondrogenic differentiation. The protocol outlines the preparation of collagen type II coating, including composition and crosslinking st

TCM-Driven Circadian Modulation in Cancer: Engineering Spatiotemporal Drug Delivery for Precision Oncology.

Circadian disruption constitutes a hallmark of cancer, driving tumorigenesis, progression, and therapy resistance via dysregulation of core clock genes. Emerging evidence indicates that traditional Chinese medicine (TCM), primarily through Chinese herbal medicine (CHM), exerts promising chronotherapeutic effects by modulating tumor-intrinsic circadian rhythms. Bioactive CHM constituents restore the oscillatory expression of clock genes (eg, BMAL1, PER2), thereby resynchronizing cell cycle control, DNA repair, metabolism, and immune surveillance to suppress malignancy. This review provides a co

Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable clinical efficacy across a spectrum of hematological malignanci … nd increasing the likelihood of on-target, off-tumor toxicity. To address these challenges, diverse engineering strategies are being developed to improve the safety, efficacy, and adaptability of CAR-T cell therapy in solid tumors. These include Boolean logic-gated receptors, multi-antigen and retargeting platforms, locoregional delivery and trafficking-enhan …

Nanobodies Open New Avenues in Cancer Treatment: From Molecular Engineering to Therapeutic Platforms.

Nanobody technology is a promising approach in cancer research and treatment. Monoclonal antibodies have long been central to targeted therapies; however, their large size, complex production, and limited tissue penetration restrict their clinical performance. Nanobodies, derived from camelid heavy-chain antibodies, possess unique properties, including small size (~15 kDa), high stability, and the ability to access otherwise inaccessible epitopes. At the molecular and cellular levels, these characteristics arise from a defined structure-function relationship that governs antigen binding, recep

Precision Oncology via Radiotherapy-Triggered Drug Delivery: Mechanisms, Molecular Engineering, and Clinical Translation.

Radiotherapy-triggered drug delivery systems (RDDS) promise to integrate the spatial precision of ionizing radiation with controllable pharmacological activation. However, clinical translation remains constrained by its reliance on supra-clinical irradiation doses. Here, we present a unifying framework redefining RDDS through two distinct paradigms: structural disassembly and molecular actuation. We delineate their radiochemical foundations, highlighting reductive and electron-driven mechanisms as more robust and tumor-selective than stochastic reactive oxygen species-mediated pathways. Furthe

Emerging frontiers in adoptive cell therapies: engineering innovations, current challenges, and manufacturing perspectives.

Immunotherapy through adoptive cell therapy (ACT) has become an effective cancer treatment method, using genetically modified immune cells or immune cells grown outside the body. The ACT methods use chimeric antigen receptor T (CAR-T) cells, with proven results for blood cancers, while tumor-infiltrating lymphocytes (TILs) and T-cell receptor (TCR)-engineered T cells serve as effective methods to fight against solid tumors and intracellular antigens. The current medical field uses natural killer (NK) cell-based therapies because of their natural ability to destroy cells, their lower incidence

Engineering controllable CAR T-cell therapies: from binary safety switches to programmable immunity.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionised cancer gene therapy, yet its expansion into solid tumours is hindered by a critical vulnerability: the autonomous, "always-on" nature of conventional CAR constructs. This unregulated activity drives severe toxicities, including cytokine release syndrome (CRS) and on-target/off-tumour damage, while constitutive signalling in hostile tumour microenvironments (TMEs) accelerates T-cell exhaustion. Early safety strategies relied on irreversible genetic "kill switches," which sacrifice the therapeutic cell population entirely. This re