Intracellular methicillin-resistant Staphylococcus aureus (MRSA) persisting within macrophages induces immunoparalysis, leading to recurrent infections. This persistence primarily arises from its metabolic dormancy, which diminishes susceptibility to antimicrobials, and from its capacity to trigger oxidative stress-mediated macrophage damage. In this study, water-soluble folic acid carbon dots (FACDs) synthesized via hydrothermal carbonization and polycondensation chelate Cu2+ and Co2+ through surface functional groups to form stable bimetallic complexes, thereby yielding degradable nanodots capable of targeted and efficient inhibition of intracellular MRSA within macrophages. First, the pterin structure of the FACDs enables specific binding to folate receptors on macrophages, facilitating cellular internalization. Second, Cu2+ disrupts the low-metabolic state of intracellular MRSA by interfering with amino acid and energy metabolism, inducing a cuproptosis-like bactericidal effect and clearing intracellular bacteria. Concurrently, Co2+ alleviates oxidative stress-induced damage in macrophages, restoring and activating their phagocytic and bactericidal functions. Furthermore, real-time monitoring with a macrophage intracellular bacterial model in vitro and MRSA bioluminescence imaging in vivo demonstrated the dynamic antibacterial process of the CDs. Collectively, this study presents an innovative strategy whereby water-soluble bimetallic FACDs enable macrophage-targeted delivery, cuproptosis-like bactericidal activity, and immunological rescue, offering a comprehensive approach to eradicate intracellular MRSA.

Multi-nozzle (MN) collaborative bioprinting enables high-precision fabrication of complex tissue and organ models through synchronous deposition of heterogeneous bioinks within a shared substrate, offering a promising solution for efficient construct generation. However, challenges remain, including nozzle motion interference and inconsistent geometric fidelity when printing asymmetric structures with heterogeneous materials. This study proposes a multi-nozzle collaborative and alternating printing path (MN-CAPP) planning strategy that integrates intra-layer repartitioning with adaptive mode switching to optimize the fabrication of complex heterogeneous tissues. By printing two Y-shaped vascular models with distinct interfaces, MN-CAPP preserves the efficiency advantages of collaborative printing for symmetric regions, improving printing efficiency by 32.4% and 33.0%, respectively, compared with single-nozzle printing. Furthermore, MN-CAPP adaptively regulates printing strategies for regions with significant nozzle step differences based on ink rheology and printing parameters. During the fabrication of size-differentiated scaffolds, the proposed path effectively suppresses edge material stack in small-scale scaffolds, resulting in a 33.8% improvement in pore diffusion degree relative to conventional collaborative printing. Finally, successful fabrication of a heterogeneous rabbit hepatobiliary model demonstrates a deviation of <= 4% in critical feature dimensions from design specifications, confirming MN-CAPP's effectiveness in enhancing both printing precision and dimensional reproducibility for complex asymmetric structures.

BACKGROUND: Autologous bone grafting is considered as "gold standard" in the alveolar ridge augmentation techniques. In situ onlay grafting uses grafts adjacent to edentulous sites without a separate donor site. Several studies have revealed the satisfactory short-term performance of this less invasive modified technique, but no information is available of stability of alveolar ridge reconstructed by in situ onlay grafting and implant performance after occlusal loading in a mid-term follow-up. This study is to retrospectively evaluate the radiographic and patient reported outcomes (PROMs) of a modified onlay grafting technique and the subsequent implantation in anterior maxilla using in situ grafts without a second bone harvesting region.; METHODS: A total of 83 patients contributed 119 edentulous deficiency sites, and 104 implants were placed in anterior maxilla. 44 patients received in situ onlay grafting using subnasal grafts and 39 patients received ex situ onlay grafting using mandibular symphysis grafts. Alveolar ridge height and multileveled widths were assessed using cone-beam computed tomography (CBCT) prior grafting and at five subsequent time points. Clinical parameters and PROMs were evaluated with a visual analog scale (VAS) during the follow-up. Approximately 6months after onlay grafting, dental implants were placed followed by fixed prosthetic rehabilitation. Implant survival and success rates were assessed with a mean follow-up of 42.90months.; RESULTS: The horizontal bone resorption at cervical level after 1-year occlusal loading of in situ group (1.73%±1.29%) was lower than that of ex situ (3.85%±1.50%) group (P=0.04). No other significant difference regarding bone resorption was found. The patient reported pain scores at 7days after surgery of in situ group (2.43±1.17) was lower than that of ex situ group (3.47±2.08, P=0.02). No implant loss was observed. The implant success rates were 96.36% in in-situ group and 97.96% in ex-situ group.; CONCLUSIONS: Within the limitations of the present retrospective study, the findings suggest that in situ onlay grafting may be a promising approach for reconstructing the anterior maxillary alveolar ridge and facilitating subsequent implant placement. These preliminary results are hypothesis-generating and warrant further validation through prospective, long-term investigations.; TRIAL REGISTRATION: This study was retrospectively registered in Chinese Clinical Trial Registry (Registration number: ChiCTR2400083954, Registration date: 2024-05-08). © 2026. The Author(s).

Methacrylated gelatin (GelMA) hydrogels have been well-recognized as a widely-used natural polymer for biofabrications due to the adaptability for multiple crosslinking schemes, desirable biocompatibility and biodegradability, and ease of chemical functionalization. With regard to 3D bioprinting, however, GelMA has shown unsatisfactory printing stability and accuracy due to slow sol-gel transition, suboptimal mechanical strength, and strict temperature control for printing. We herein developed an innovative dual-crosslinkable colloidal inks composed of self-assembled GelMA nanospheres with 80 % self-healing efficiency, which outperform the traditional GelMA polymeric inks in terms of enhanced printability and fidelity, broader printing temperature range, adjustable mechanical strength ranging from brain analogue 2.83 kPa to cardiac analogue 52.45 kPa, and improved bio-functionalities evidenced by the elevated hydrophilicity, mass transfer efficiency and prolonged drug release profile. Moreover, the granulation design of GelMA inks unlocked freeform 3D printing modes such as direct multi-ink writing, embedded printing, but also allowed in-situ printing directly at the bleeding wound sites due to the outstanding hemostatic efficacy and network stability of colloidal gels. In general, our nanostructured GelMA colloidal inks present a better replacement for the traditional GelMA polymeric inks in 3D bioprinting, which establishes a foundation for bench-to-bedside translations of 3D printing techniques towards more practical clinical applications.

Craniofacial muscles are essential components of the skeletal muscular system that contribute to important physiological processes. Severe trauma can induce craniofacial volumetric muscle loss (VML), which impairs muscle regeneration, causes facial muscular deformities and functional disability, and leads to psychosocial consequences such as isolation and depression. Conventional therapies involving muscle flap transposition or autologous tissue grafting achieve morphological repair but are ineffective in restoring muscle function, resulting in donor site injury and sensory deficit. In this study, we successfully constructed a biomimetically engineered muscle tissue that integrates myofiber alignment, effective innervation, and blood perfusion to promote multi-tissue regeneration in the masseter area in vivo, enabling functional regeneration. Using light-controlled micropatterning technology, we constructed mature muscle fibers with oriented alignment and established a neuromuscular co-culture system for in vitro neuromuscular junction reconstruction. Furthermore, we designed and fabricated a vascular network structure to promote tissue vascularization using hydrogel as the vehicle for assembling the composite engineered tissue. Using this technology, the shape and dimension of the constructed entity can be customized to address various muscle defects, enabling individualized repair. This study offers a promising novel strategy for tissue regeneration that breaks through the current challenges in the treatment of craniofacial VML.[GRAPHICS].

Peripheral nerve injuries are a prevalent global issue that has garnered great concern. Although autografts remain the preferred clinical approach to repair, their efficacy is hampered by factors like donor scarcity. The emergence of nerve guidance conduits as novel tissue engineering tools offers a promising alternative strategy. This review aims to interpret nerve guidance conduits and their commercialization from both clinical and laboratory perspectives. To enhance comprehension of clinical situations, this article provides a comprehensive analysis of the clinical efficacy of nerve conduits approved by the United States Food and Drug Administration. It proposes that the initial six months post-transplantation is a critical window period for evaluating their efficacy. Additionally, this study conducts a systematic discussion on the research progress of laboratory conduits, focusing on biomaterials and add-on strategies as pivotal factors for nerve regeneration, as supported by the literature analysis. The clinical conduit materials and prospective optimal materials are thoroughly discussed. The add-on strategies, together with their distinct obstacles and potentials are deeply analyzed. Based on the above evaluations, the development path and manufacturing strategy for the commercialization of nerve guidance conduits are envisioned. The critical conclusion promoting commercialization is summarized as follows: 1) The optimization of biomaterials is the fundamental means; 2) The phased application of additional strategies is the emphasized direction; 3) The additive manufacturing techniques are the necessary tools. As a result, the findings of this research provide academic and clinical practitioners with valuable insights that may facilitate future commercialization endeavors of nerve guidance conduits. © 2025 The Authors

The designing and manufacturing of micro/nanoscale tools for delivery, diagnostic, and therapeutic are essential for their multiscale integration in the precision medicine field. Conventional three-dimensional (3D) printing approaches are not suitable for such kind of tools due to the accuracy limitation. Multiphoton polymerization (MPP)-based micro/nanomanufacturing is a noncontact, high-precision molding technology that has been widely used in the micro/nano field is a promising tool for micro/nanoscale related precision medicine. In this article the fundamentals of MPP-based technology and the required materials in precision medicine are overviewed. The biomedical applications in various scenarios are then summarized and categorized as delivery systems, microtissue modeling, surgery, and diagnosis. Finally, the existing challenges and future perspectives on MPP-based micro/nanomanufacturing for precision medicine are discussed, focusing on material design, process optimization, and practical applications to overcome its current limitations. © 2024 THE AUTHORS

Embedded ink writing (EIW) is an emerging 3D printing technique that fabricates complex 3D structures from various biomaterial inks but is limited to a printing speed of 10mms-1 due to suboptimal rheological properties of particulate-dominated yield-stress fluids when used as liquid baths. In this work, a particle-hydrogel interactive system to design advanced baths with enhanced yield stress and extended thixotropic response time for realizing high-speed EIW is developed. In this system, the interactions between particle additive and three representative polymeric hydrogels enable the resulting nanocomposites to demonstrate different rheological behaviors. Accordingly, the interaction models for the nanocomposites are established, which are subsequently validated by macroscale rheological measurements and advanced microstructure characterization techniques. Filament formation mechanisms in the particle-hydrogel interactive baths are comprehensively investigated at high printing speeds. To demonstrate the effectiveness of the proposed high-speed EIW method, an anatomic-size human kidney construct is successfully printed at 110mms-1, which only takes 4h. This work breaks the printing speed barrier in current EIW and propels the maximum printing speed by at least 10 times, providing an efficient and promising solution for organ reconstruction in the future. © 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

Regeneration and reconstruction of bone tissue is always a challenge for clinicians due to the uncertainty of bone repair materials in terms of long-term and efficient effects on osteoblasts. Here, we propose a novel strategy combining benidipine, an antihypertensive drug and nanoparticles to synergistically promote the healing of bone defects. Loose and porous benidipine-loaded magnesium silicate nanoparticles were prepared and validated for their biosafety. The nanoparticles were efficiently taken up by preosteoblasts and uniformly distributed around the nucleus. After internalization into cells, the nanosystem is degraded by lysosomes, and the effect of promoting osteogenic differentiation is reflected by the continuous release of benidipine, silicon and magnesium ions. Our results clearly evaluated that the nanoflower-like magnesium silicate delivering benidipine tends to bemoreappropriateforthebone regeneration in preosteoblasts, indicating that it might be a potential approach in guiding bone repair in clinical applications. Graphic abstract: [Figure not available: see fulltext.] © 2023, Zhejiang University Press.

The small intestine's intricate structure enables vital functions such as nutrient absorption, microbial defense, and barrier protection, yet replicating its complexity in vitro remains a substantial challenge. We engineered a three-dimensional bioprinted intestinal model featuring biomimetic circular folds and zonated shear stress distribution to recapitulate native physiology. A filament-resolved embedded bioprinting approach enabled high-fidelity fabrication of thin-walled, continuous structures that shaped physiologically relevant flow microenvironments essential for epithelial development. These shear stress patterns regulated tight junctions, secretory activity, and transporter expression, driving region-specific epithelial specialization into barrier or absorptive phenotypes. Coculture with probiotic Lactobacillus plantarum activated localized immune responses and modulated epithelial function through spatially distinct colonization. Regional flow differences governed the transport of nutrient and drug probes via transcellular and paracellular pathways. Quantitative assessment of drug absorption demonstrated strong in vitro-in vivo correlation, validating physiological relevance. By unifying structural, mechanical, and functional complexity, this platform advances intestinal models for studying physiology, host-microbe interactions, and drug transport.