Magnetic microrobots hold immense potential for various biomedical applications, including targeted drug delivery. However, their operational efficacy in complex, heterogeneous biological environments (e.g., vasculature with varying lumen diameters) is often constrained. To address this limitation, this study presents a magnetically driven soft microrobot capable of dual-mode locomotion, where seamless switching between oscillatory and helical motions is achieved solely by switching the external magnetic field frequency via frequency modulation. The proposed microrobot, with a millimeter-scale architecture featuring a programmed magnetization profile, exhibits C-shaped oscillation at low frequencies for rapid propulsion and terrain adaptation, and transforms into a helical rotation at high frequencies for stable navigation within confined channels. Experiments were conducted in a glycerol–water mixture to reveal that oscillatory and helical motion modes each operate within distinct, non-overlapping frequency bands. The microrobot successfully performed navigation through mode switching in both a biomimetic vascular model and ex vivo porcine organs. Furthermore, by integrating a photothermal-responsive methacrylated gelatin (GelMA) drug carrier, we demonstrated successful targeted drug delivery at a designated site triggered by near-infrared irradiation after magnetically guided delivery in a dynamic flow environment.
为克服现有进口器械热损伤风险高、 与国内临床常用的 6 Fr 鞘管不兼容等局限性, 我们研发了一款名为 Saphenus 的新型国产射频消融 (RFA) 导管系统。 其核心创新点包括: 6 Fr 外径设计 (适配国内常用鞘管), 独特的双模工作长度设计 (8 mm 用于穿通静脉, 80 mm 用于大隐静脉), 以及优化的温度传感机制以提供精准的热反馈。 体外测试及山羊动物实验结果表明, Saphenus 系统可实现有效的血管闭合。 术后超声及组织病理学分析证实, 所有靶静脉均成功闭塞且未见再通, 其疗效与对照组相当, 但热损伤风险显著降低。 综上, 该系统为下肢静脉功能不全提供了一种安全、 高效且经济的微创治疗方案, 尤其契合中国临床实际需求。
Patient-derived colorectal cancer organoids (CRCOs) are increasingly recognized for their ability to preserve genetic, transcriptional, histological, and drug-responsive features of the original colorectal tumors, offering promise in precision medicine and drug development. While the conventional Matrigel dome culture (DOME) approach has been instrumental in enabling valuable investigations, it has limitations—most notably considerable variation in organoid size and drug sensitivity profiles. In this study, we developed an organoid-on-a-chip (CHIP) for forming uniform organoids and improving precision drug evaluation. Specifically, we fabricated the CHIP using three-dimensional (3D)-printing and micro-molding techniques. Using this CHIP, 19 uniform CRCOs can be generated concurrently in a single well of a 96-well plate within three days, each forming from a minimal seeding density of only 100 cells. Furthermore, the CHIP facilitates in situ imaging and continuous monitoring of individual organoids, supporting label-free, morphometric analysis-based drug screening. Organoids cultured on the CHIP show significantly improved consistency, uniformity, and reproducibility over the DOME method. Our CHIP organoids are functionally identical to conventional DOME organoids, but exhibit greater reliability in drug screening. These results support the CHIP’s potential for high-throughput assays and predictive drug screening models.
Embedded ink writing has been extensively applied in recent years for various biomedical applications. Despite its outstanding ability to create complex structures, the challenge of optimizing multiple factors has hampered further utilization of this three-dimensional bioprinting strategy. In this work, we experimentally summarized the coupling effects of ink viscosity, support bath rheological properties, and key printing parameters on filament formation. Based on the gathered data, Bayesian optimization is used to establish a filament prediction platform, which can accurately estimate the rheology of support baths for printing alginate-based ink under the given conditions. Additionally, the platform is used to predict the optimal parameters for printing with chitosan ink. Two representative eye-relevant tissues are successfully fabricated using the predictions of the platform. The insights from this study lay the foundation for embedded ink writing strategies that can guide support bath design and identify optimal printing parameters, aiding efficient reconstruction of human tissues and organs in the future.
Biofabrication and biomedical manufacturing are inherently multidisciplinary, integrating living systems with advanced manufacturing to create functional products for applications spanning regenerative engineering and medicine, in vitro disease modeling, drug discovery, and medical devices. As these technologies develop, they are emerging as core enablers of next-generation healthcare and life-science innovation. In the United States (U.S.), rapid progress across fabrication processes, material systems, physics-based modeling, and translation-oriented strategies is expanding the achievable design space and accelerating movement from laboratory demonstrations toward clinical and commercial deployment. We introduce major U.S. research frontiers and highlight representative advances in this field that support applications including organoids and other microphysiological systems for in vitro testing, engineered tissue constructs for in vivo use, and medical devices and biohybrid platforms. We further provide an outlook on advancing robust, ethical biofabrication and biomedical manufacturing in the U.S. research ecosystem.
Developmental tissue engineering is increasingly guided by the principles of morphogenesis, cellular self-organization, and dynamic microenvironmental regulation, moving beyond static scaffold design and towards adaptive, development-inspired strategies. Integrating insights from developmental biology has revealed new structural-functional relationships and more robust tissue maturation pathways, thereby unlocking biofabrication strategies that harness intrinsic biological regulatory mechanisms rather than imposing static architectures on engineered tissue. This review examines machine learning (ML) applications to tissue engineering within a developmental context, emphasizing how bioelectric, biomechanical, and morphogenic cues influence cell fate, tissue organization, and adaptive growth. We highlight how data-driven and physics-based models, surrogate modeling, and generative design can integrate complex biological data, simulate evolving microenvironments, and guide experimental biofabrication. Despite these advances, significant challenges remain, such as the integration of heterogeneous and multiscale biological data, limitations in model interpretability and generalizability, and ethical and regulatory considerations regarding data use and artificial intelligence (AI)-guided decision-making in biofabrication applications. Through the coupling of developmental principles with computational tools, ML-driven tissue engineering is nevertheless well positioned to enable more predictive, adaptive, and reproducible paradigms for creating functional living systems.
Traumatic injuries to the craniofacial skeleton, along with diseases and structural defects affecting oral tissues—including teeth, gums, and the periodontal complex—are among the most prevalent pathological conditions in humans. Over the course of a lifetime, nearly everyone requires some form of dental or maxillofacial care. While current routine clinical procedures—such as surgical reconstructions, tissue grafting, and prosthetic restoration—provide varying degrees of therapeutic benefit, they often fail to fully restore the complex architecture and functions of craniofacial tissues. This limitation primarily reflects the intricate organization of the maxillofacial region, in which soft and hard tissues are tightly coordinated within a precisely regulated anatomical framework. Emerging cell-based biofabrication technologies, such as organoids, three-dimensional bioprinting, and microfluidic organ-on-chip systems, offer promising strategies for improving tissue equivalents and in vitro tissue models, bringing their architecture and functional properties closer to native tissues. In this review, we examine recent advances in craniofacial cell-based biofabrication, focusing on the development of oral tissue organoids, advanced bioprinting techniques—including in situ bioprinting, four-dimensional bioprinting, and volumetric bioprinting—and the implementation of craniofacial organ-on-chip systems. Furthermore, we discuss the principal challenges currently limiting the field and outline prospective directions that may guide the next generation of cranial and oral tissue engineering.
Chronic wound healing remains challenging due to the risk of bacterial infection and the typical microenvironments characterized by oxidative stress, hypoxia, and insufficient angiogenesis. Herein, a hydrogel dressing (CLIHO) has been developed to efficiently promote the healing of methicillin-resistant Staphylococcus aureus (MRSA) infected wounds by integrating near-infrared (NIR)-controlled cascade reactions among hemin, indocyanine green (ICG), and l-arginine (l-Arg). Mild heat (approximately 45 °C) and cascade generation of reactive oxygen species (ROS), nitric oxide (NO), and ONOO− from the CLIHO hydrogel have been demonstrated under NIR irradiation. Benefiting from the O2 supplied by hemin-mediated decomposition of endogenous excess H2O2 in wounds, CLIHO hydrogel demonstrated hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial activity, enabling it to effectively inhibit MRSA, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis) proliferation, as well as eradicate the formed biofilms. The antibacterial performance of the CLIHO hydrogel was significantly superior to that of the CIO hydrogel with phototherapy alone and the CLIO hydrogel without O2 supply. Upon NIR turn-off, the CLIHO hydrogel could remodel the microenvironment of chronic wounds by scavenging excessive ROS, reducing local H2O2 levels, and alleviating hypoxia while promoting angiogenesis by releasing trace amounts of NO under endogenous nitric oxide synthase. Importantly, compared with CLIO hydrogel (without hemin), the CLIHO hydrogel significantly accelerated the high-quality healing of MRSA-infected wounds by efficiently eliminating bacterial infection, balancing inflammatory responses, and promoting angiogenesis and collagen deposition. Hence, the prepared CLIHO hydrogel integrating NIR-controlled cascade reaction provides an efficient and secure dressing for accelerating healing of MRSA-infected wounds via hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial and microenvironment remodeling.
Arrhythmia is a critical clinical manifestation of cardiovascular disease; however, current therapeutic strategies are limited by significant side effects or high invasiveness. Kuanxiong aerosol (KXA), a traditional Chinese medicine (TCM) formulation clinically used for the relief of angina pectoris, exhibits multi-component and multi-target characteristics that suggest potential antiarrhythmic properties. However, direct cellular-level electrophysiological evidence is lacking. This study established an in vitro myocardial sensing model based on microelectrode array (MEA) technology. This platform supports non-invasive, real-time monitoring with parallel multi-site recording capability and has been used to systematically evaluate KXA’s intervention effects on various types of arrhythmias. We successfully constructed an MEA-based sensing platform using primary rat cardiomyocytes and determined a safe and effective KXA concentration. On this basis, we developed pathological models simulating chronic degenerative lesions and acute drug-induced bradycardia to assess the regulatory effects of KXA on myocardial electrical activity. Experimental results demonstrated that KXA effectively increased cardiomyocyte firing rate, enhanced electrical signal amplitudes, and restored the rhythmicity of calcium transients. This study reveals KXA’s multidimensional intervention effects on arrhythmias and successfully integrates advanced MEA biosensing technology into the dynamic pharmacodynamic evaluation of TCM compounds, providing an innovative bioengineering method for assessing the cardiac function of complex drug systems.
Zebrafish (Danio rerio) larvae are optically transparent, small vertebrates that serve as an ideal model for in vivo high-throughput screening. However, automated high-throughput manipulation, imaging, and analysis of live zebrafish larvae remain considerable challenges. Moreover, it is critical to avoid damage to these delicate organisms because even minor injury can impair normal physiological function. To address these challenges, we developed a high-throughput manipulation platform that enables the loading of zebrafish larvae into glass tubes, enabling accurate localization and controlled rotation at a throughput of one fish every 15 s. The platform uses hydrodynamic methods, including a siphon-based system, as the primary driving mechanism to enable adaptive loading and unloading of zebrafish larvae while substantially reducing fluid pressure and minimizing potential flow-induced damage. In addition, the platform integrates machine vision to support automated control and data acquisition throughout the entire workflow. We developed a comprehensive suite of algorithms for automated image segmentation of zebrafish larval videos and three-dimensional (3D) reconstruction of their transparent structures and internal organs. Two distinct 3D reconstruction algorithm pipelines were designed: one is a computationally efficient, lightweight approach optimized for execution on conventional personal computers; the other is a high-speed rendering-based algorithm that requires large-memory computational resources to achieve reconstructions at the original image resolution. Notably, both approaches operate without requiring any additional user-defined parameter tuning. Finally, we demonstrate the platform’s capability by evaluating drug-induced inhibition of zebrafish melanogenesis. This automated platform expands the utility of zebrafish as a versatile, high-throughput model system, facilitating research across diverse fields, including developmental biology, disease modeling, and pharmaceutical and toxicological evaluation.
The viability assessment of patient-derived tumor organoids is essential for preclinical drug screening, with microscopic imaging serving as a key method for evaluating drug effects. Traditional image analysis methods, such as manual evaluation and fluorescence staining, suffer from low efficiency, dye toxicity, and fluorescence degradation, making them unsuitable for high-throughput drug screening. Additionally, current artificial intelligence (AI)-based tools face challenges in precise segmentation for the accurate quantitative analysis of viable and nonviable organoids. To address these challenges, we introduce OrganoidViT, a novel deep learning model utilizing vision transformer technology for the precise segmentation of viable and nonviable colorectal cancer organoids in bright-field microscopy images, ensuring an accurate efficacy assay of different drugs. Trained on custom datasets of colorectal cancer organoids prepared using microdroplet technology, OrganoidViT facilitates high-throughput segmentation without fluorescence imaging, with experimental results indicating superior performance of OrganoidViT (accuracy of 99.7
Tomographic volumetric bioprinting (TVBP) is an emerging transformative technology in bio-manufacturing, distinguished by two exceptional capabilities: ultrafast fabrication (centimeter-scale constructs within tens of seconds) and unique compatibility with ultra-soft bioinks (<102 Pa). Despite its potential, TVBP remains in its infancy because of significant hurdles. These include the need to adapt conventional photocurable bioinks to TVBP’s unique photopolymerization requirements and achieve sufficient resolution to replicate intricate multicellular structures. Therefore, this review outlines strategies to address these challenges, delving into (1) the development of suitable bioinks, (2) printing resolution optimization, and (3) rapid construction of complex biological structures and functions. Furthermore, the fundamental principles and evolution of projection slicing algorithms are explored, and the latest advancements in TVBP applications are summarized. Finally, we explore the future trajectory of this promising bio-manufacturing technology.
Advanced therapy medicinal products are biological products that require rigorous long-term monitoring of safety and efficacy due to their sustained effects. The development of tissue-engineered products demands careful consideration of tissue-specific properties, surgical requirements, biomaterial compatibility, host tissue integration, and potential immune responses. In this study, we developed and evaluated the safety and efficacy of 3D-bioprinted constructs containing cells for bone regeneration in preclinical models. Three types of human mesenchymal stem cells (bone marrow-derived, adipose-derived, and nasal turbinate-derived) were combined with varying concentrations of collagen and polycaprolactone. Safety assessments included comprehensive tumorigenicity evaluations involving cell viability assays, protein quantification, and whole-genome sequencing under multiple conditions to confirm genetic stability and mitigate tumorigenic risks. Short-term toxicity was evaluated by subcutaneous implantation in nude mice, with blood and serum analyses confirming the absence of acute toxicity or histological abnormalities in major organs. Efficacy studies in rabbits exhibited safety through posttransplantation analyses, with 6-month tissue analyses showing significantly elevated expression of osteopontin and runt-related transcription factor 2 (RUNX2) proteins in constructs containing human nasal turbinate-derived mesenchymal stem cells, indicating successful tissue integration and bone-specific marker expression. Long-term follow-up confirmed construct integrity and sustained bone formation. These findings highlight the importance of comprehensive safety and efficacy evaluations across cell types and construct compositions in the development of 3D-bioprinted constructs for bone regeneration. This study establishes a systematic framework for material selection and validation in preclinical stages, providing a foundation for future clinical applications in regenerative medicine and tissue engineering.
Efficient coupling between acoustic fields and fluid microenvironments is crucial for advancing applied physics and microfluidic engineering in advanced biomedical, environmental sustainability, and broader industrial applications. Harnessing such interactions for biological processing enables the precise, contactless, and tunable control of cell membrane disruption, facilitating reagent-free, contamination-minimized lysis. However, existing acoustic lysis devices are faced with challenges of limited efficiency and intricate structures. To overcome these limitations, we developed a staggered traveling-surface Rayleigh acoustic wave (STRAW) microchip for additive-free cell lysis. The device consists of a LiNbO3 substrate patterned with two sets of interdigital transducers and a circular polydimethylsiloxane ring for confining cell suspension. We constructed a mathematical model for the STRAW-induced mechanical effects and optimized the alignment of interdigital transducers via theoretical modeling and finite-element analysis to maximize torque and acoustic streaming. The proposed STRAW-based platform showed over 95
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Nanomedicine has enormous potential in the diagnosis and treatment of malignant neoplasms.However,the clinical transla-tion of various nanoparticles(NPs)as drug delivery systems(DDSs)for tumor therapy remains poor.The main bottleneck is the limited database on the correlation between the design of NPs with unique physicochemical features and their therapeutic efficiency.In this study,we aim to design and investigate structurally variant nanocarriers composed of polylactide(PLA),silicon dioxide(SiO2),calcium carbonate(CaCO3),and barium carbonate(BaCO3)to reveal the relationship between their physicochemical features and therapeutic effectiveness against melanoma in vitro and in vivo.Specifically,we(1)examined their morphology,size,and structural characteristics;(2)evaluated colloidal stability;(3)verified the drug-loading and re-lease efficiency of a 2-aminothiophene scaffold(2AmT);(4)investigated cellular uptake and tumor spheroid penetration effi-ciency;(5)analyzed in vivo biodistribution;and(6)estimated therapeutic efficiency.The main characteristics of inorganic and organic NPs were collected and compared systematically.Considering the advantages and drawbacks of each NP type,the following tumor growth inhibition against melanoma was observed:CaCO3(87.9%-93.4%for 0.4 g/kg of 2AmT)>SiO2(75.6%-93.2%for 0.4 g/kg of 2AmT)>PLA(80.3%-88.2%for 0.4 g/kg of 2AmT)>BaCO3(58.8%-83.7%for 0.4 g/kg of 2AmT).Thus,this study contributes to the development of fundamental nanomedicine and accelerates the clinical translation of nanocarriers for effective melanoma therapy.
Amino acid non-centrosymmetric self-assemblies, possessing inherent polarization as well as biocompatibility, can be employed as bioinspired alternatives for the development of implantable piezoelectric bioelectronics. This could enable the harvesting of biomechanical energy for in situ in vivo monitoring and avoid the need for secondary surgeries, potentially overcoming the trade-off between high-efficiency sensing and the biosafety limitations of traditional inorganic or polymeric piezoelectric counterparts. In this regard, the electromechanical coupling behaviors of the minimalistic metabolite self-assemblies are reported. Experimental tests reveal that compared to other natural amino acid crystals, threonine (T) crystals exhibit a high Young’s modulus of up to approximately 80 GPa by forming a denser three-dimensional hydrogen-bonding network, with each molecule interacting with seven adjacent ones. Computational analysis reveals that side-chain entities dramatically affect crystal packing, with polar hydroxyl moieties accounting for the distinct piezoelectric features underlying the macroscopic performance. This highlights the potential of exploiting T crystals to develop biodegradable piezoelectric bioelectronics that exhibit highly sensitive linear responses for tactile sensing and post-implantation in vivo motion monitoring. This study demonstrates the feasibility of exploiting minimalistic metabolite self-assemblies for piezoelectric bioelectronics in bio-machine interface and biomedical engineering applications.
Pulsatile drug delivery, in which rapid drug release is separated by defined lag periods, offers significant therapeutic advantages but is limited by the need for repeated injections and poor patient adherence. Here, we introduce the fused device (FUSED), a subcutaneous system enabling programmed multidose drug delivery through a single implantation. FUSED comprises paired delay and shot units that regulate dosing intervals and trigger pulsatile drug release, respectively. After implantation, body fluids gradually dissolve the microfuse in each delay unit, with the delay duration determined by fuse length. Once fluid reaches a shot unit, an effervescent reaction is initiated, producing rapid drug release. In vitro and in vivo evaluations demonstrated precise pulsatile release of the model antigen ovalbumin, effectively reproducing prime–boost vaccination timing and eliciting the corresponding immune response. These results suggest that FUSED may provide a viable alternative to repeated injections and improve adherence in multidose therapeutic regimens.
Reversible electroporation (RE) involves applying pulsed electric fields to briefly disrupt cell membrane channels, allowing molecular transfer while preserving cell viability. Advances in RE combined with micro- and nano-devices have improved efficiency and safety in cellular analysis and engineering, holding substantial promise for biological research and precision medicine. This review summarizes progress in RE technology, spanning underlying theoretical principles, practical implementation, and emerging applications. By integrating mechanistic insights with parameter assessment, we strengthen process understanding of RE to support further optimization. To clarify RE implementation strategies, we present advances in micro- and nano-devices based on varying electric field control approaches. Using these platforms, we examine improvements in intracellular analysis, cellular engineering, drug delivery, and cell sampling to illustrate state-of-the-art RE applications. Finally, we outline future directions and trends for RE systems aimed at molecular mechanism mapping and personalized precision medicine, emphasizing their increasing relevance in practical settings.
