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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Fabrication of versatile poly(xylitol sebacate)-co-poly(ethylene glycol) hydrogels through multifunctional crosslinkers and dynamic bonds for wound healing

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Acta Biomaterialia 2023年 170卷 344-359页

作者： Yeh, Ying-Yu Lin, Yi-Yun Wang, Ting-Teng Yeh, Yu-Jia Chiu, Ting-Hsiang Wang, Reuben Bai, Meng-Yi Yeh, Yi-Cheun Institute of Polymer Science and Engineering National Taiwan University Taipei Taiwan Institute of Biomedical Engineering National Taiwan University Taipei Taiwan Biomedical Engineering Program Graduate Institute of Applied Science and Technology National Taiwan University of Science and Technology Taipei Taiwan Institute of Food Safety and Health National Taiwan University Taipei Taiwan Graduate Institute of Biomedical Engineering National Taiwan University of Science and Technology Taipei Taiwan Adjunct Appointment to the Department of Biomedical Engineering National Defense Medical Center Taipei Taiwan Program National Taiwan University Taipei Taiwan GIP-TRIAD Master's Degree in Agro-Biomedical Science National Taiwan University Taipei Taiwan

Poly(polyol sebacate) (PPS) polymer family has been recognized as promising biomaterials for biomedical applications with their characteristics of easy production, elasticity, biodegradation, and cytocompatibility. Poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG) has been developed to fabricate PPS-based hydrogels;however, current PXS-co-PEG hydrogels presented limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. Here, we fabricate a new type of PXS-co-PEG hydrogels through the use of multifunctional crosslinkers as well as dynamic bonds. In our design, polyethyleneimine-polydopamine (PEI-PDA) macromers are utilized to crosslink aldehyde-functionalized PXS-co-PEG (APP) through imine bonds and hydrogen bonds. PEI-PDA/APP hydrogels present multiple functional properties (e.g., fluorescent, elastomeric, biodegradable, self-healing, bioadhesive, antioxidant, and antibacterial behaviors). These properties of PEI-PDA/APP hydrogels can be fine-tuned by changing the PDA grafting degrees in the PEI-PDA crosslinkers. Most importantly, PEI-PDA/APP hydrogels are considered promising wound dressings to promote tissue remodeling and prevent bacterial infection in vivo. Taken together, PEI-PDA/APP hydrogels have been demonstrated as versatile biomaterials to provide multiple tailorable properties and desirable functions to expand the utility of PPS-based hydrogels for advanced biomedical applications. Statement of significance: Various strategies have been developed to fabricate poly(polyol sebacate) (PPS)-based hydrogels. However, current PPS-based hydrogels present limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. This work describes that co-engineering crosslinkers and interfacial crosslinking is a promising approach to synthesizing a new type of poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-

关键词： Polyols

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The Edifice of Vasculature-On-Chips: A Focused Review on the Key Elements and Assembly of Angiogenesis Models

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ACS Biomaterials Science and engineering 2024年第6期10卷 3548-3567页

作者： Lim, Joshua Fang, Hsu-Wei Bupphathong, Sasinan Sung, Po-Chan Yeh, Chen-En Huang, Wei Lin, Chih-Hsin Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan High-value Biomaterials Research and Commercialization Center National Taipei University of Technology Taipei10608 Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan35053 Taiwan School of Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Department of Orthodontics Rutgers School of Dental Medicine NewarkNJ07103 United States

The conception of vascularized organ-on-a-chip models provides researchers with the ability to supply controlled biological and physical cues that simulate the in vivo dynamic microphysiological environment of native blood vessels. The intention of this niche research area is to improve our understanding of the role of the vasculature in health or disease progression in vitro by allowing researchers to monitor angiogenic responses and cell-cell or cell-matrix interactions in real time. This review offers a comprehensive overview of the essential elements, including cells, biomaterials, microenvironmental factors, microfluidic chip design, and standard validation procedures that currently govern angiogenesis-on-a-chip assemblies. In addition, we emphasize the importance of incorporating a microvasculature component into organ-on-chip devices in critical biomedical research areas, such as tissue engineering, drug discovery, and disease modeling. Ultimately, advances in this area of research could provide innovative solutions and a personalized approach to ongoing medical challenges. © 2024 The Authors. Published by American Chemical Society.

关键词： Endothelial cells

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Enhanced Vascular-like Network Formation of Encapsulated HUVECs and ADSCs Coculture in Growth Factors Conjugated GelMA Hydrogels

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ACS Biomaterials Science and engineering 2024年第5期10卷 3306-3315页

作者： Bupphathong, Sasinan Lim, Joshua Fang, Hsu-Wei Tao, Hsuan-Ya Yeh, Chen-En Ku, Tian-An Huang, Wei Kuo, Ting-Yu Lin, Chih-Hsin Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan High-Value Biomaterials Research and Commercialization Center National Taipei University of Technology Taipei10608 Taiwan Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan35053 Taiwan School of Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan Department of Orthodontics Rutgers School of Dental Medicine NewarkNJ07103 United States

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering. © 2024 The Authors. Published by American Chemical Society.

关键词： Hydrogels

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Overcoming Cytosolic Delivery Barriers of Proteins Using Denatured Protein-Conjugated Mesoporous Silica Nanoparticles

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ACS Applied Materials and Interfaces 2023年第1期15卷 432-451页

作者： Dembélé, Julien Liao, Jou-Hsuan Liu, Tsang-Pai Chen, Yi-Ping Graduate Institute of Biomedical Materials & Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Laboratory of Toxicology Environment and Health Doctorate School of Health University Joseph Ki-Zerbo Ouaga03 BP 7021 Burkina Faso Department of Chemistry National Taiwan University Taipei10617 Taiwan Department of Surgery Mackay Memorial Hospital Taipei10449 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan

Intracellular delivery of therapeutic proteins has increased advantages over current small-molecule drugs and gene therapies, especially in therapeutic efficacies for a broad spectrum of diseases. Hence, developing the protein therapeutics approach provides a needed alternative. Here, we designed a mesoporous silica nanoparticle (MSN)-mediated protein delivery approach and demonstrated effective intracellular delivery of the denatured superoxide dismutase (SOD) protein, overcoming the delivery challenges and achieving higher enzymatic activity than native SOD-conjugated MSNs. The denatured SOD-conjugated MSN delivery strategy provides benefits of reduced size and steric hindrance, increased protein flexibility without distorting its secondary structure, exposure of the cell-penetrating peptide transactivator of transcription for enhanced efficient delivery, and a change in the corona protein composition, enabling cytosolic delivery. After delivery, SOD displayed a specific activity around threefold higher than in our previous reports. Furthermore, the in vivo biosafety and therapeutic potential for neuron therapy were evaluated, demonstrating the biocompatibility and the effective antioxidant effect in Neuro-2a cells that protected neurite outgrowth from paraquat-induced reactive oxygen species attack. This study offers an opportunity to realize the druggable possibility of cytosolic proteins using MSNs. © 2022 American Chemical Society.

关键词： Peptides

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Downsizing and soft X-ray tomography for cellular uptake of interpenetrated metal-organic frameworks

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Journal of Materials Chemistry B 2024年第25期12卷 6079-6090页

作者： Yu, Yu-Sheng Liang, Yung-Yi Hsieh, Chia-Chun Lin, Zi-Jing Cheng, Po-Hsiu Cheng, Chih-Chan Chen, Shu-Ping Lai, Lee-Jene Wu, Kevin C.-W. National Taiwan University Department of Chemical Engineering Taipei Taiwan National Health Research Institute Institute of Biomedical Engineering and Nanomedicine Miaoli Taiwan Hsinchu Taiwan International Graduate Program of Molecular Science and Technology Taiwan International Graduate Program Academia Sinica Taipei Taiwan National Taiwan University Taipei Taiwan

Metal-organic frameworks (MOFs) are porous materials with potential in biomedical applications such as sensing, drug delivery, and radiosensitization. However, how to tune the properties of the MOFs for such applications remains challenging. Herein, we synthesized two MOFs, Zr-PEB and Hf-PEB. Zr-PEB can be classified as porous interpenetrated zirconium frameworks (PIZOFs) and Hf-PEB is its analogue. We controlled their sizes while maintaining their crystal structure by employing a coordination modulation strategy. They were designed to serve as sensitizer for X-ray therapy and as potential drug carriers. Comprehensive characterizations of the MOFs' properties have been conducted, and the in vitro biological impacts have been studied. Since viability assay showed that Hf-PEB was more biocompatible compared to Zr-PEB, the cellular uptake of Hf-PEB by cells was evaluated using both fluorescence microscopy and soft X-ray tomography (SXT), and the three-dimensional structure of Hf-PEB in cells was observed. The results revealed the potential of Zr-PEB and Hf-PEB as nanomaterials for biomedical applications and demonstrated that SXT is an effective tool to assist the development of such materials. © 2024 The Royal Society of Chemistry.

关键词： Organometallics

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One-Pot Multi-frame Denoising

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International Journal of Computer Vision 2024年第2期132卷 515-536页

作者： Jin, Lujia Guo, Qing Zhao, Shi Zhu, Lei Chen, Qian Ren, Qiushi Lu, Yanye Institute of Medical Technology Peking University Health Science Center Peking University Beijing100191 China Department of Biomedical Engineering College of Future Technology Peking University Beijing100871 China Institute of Biomedical Engineering Peking University Shenzhen Graduate School Shenzhen518055 China Institute of Biomedical Engineering Shenzhen Bay Laboratory Shenzhen518071 China National Biomedical Imaging Center Peking University Beijing100871 China Chinese Academy of Cultural Heritage Beijing100029 China School of Physics Peking University Beijing100871 China

The efficacy of learning-based denoising techniques is heavily reliant on the quality of clean supervision. Unfortunately, acquiring clean images in many scenarios is a challenging task. Conversely, capturing multiple noisy frames of the same field of view is feasible and natural in real-life scenarios. Thus, it is imperative to explore the potential of noisy data in model training and avoid the limitations imposed by clean labels. In this paper, we propose a novel unsupervised learning strategy called one-pot denoising (OPD), which is the first unsupervised multi-frame denoising method. OPD differs from traditional supervision schemes, such as supervised Noise2Clean, unsupervised Noise2Noise, and self-supervised Noise2Void, as it employs mutual supervision among all the multiple frames. This provides learning with more diverse supervision and allows models to better exploit the correlation among frames. Notably, we reveal that Noise2Noise is a special case of the proposed OPD. We provide two specific implementations, namely OPD-random coupling and OPD-alienation loss, to achieve OPD during model training based on data allocation and loss refine, respectively. Our experiments demonstrate that OPD outperforms other unsupervised denoising methods and is comparable to non-transformer-based supervised N2C methods for several classic noise patterns, including additive white Gaussian noise, signal-dependent Poisson noise, and multiplicative Bernoulli noise. Additionally, OPD shows remarkable performance in more challenging tasks such as mixed-blind denoising, denoising random-valued impulse noise, and text removal. The source code and pre-trained models are available at https://***/LujiaJin/One-Pot_Multi-Frame_Denoising . © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

关键词： Unsupervised learning

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Adjustable polymer dispersed liquid crystal grating

Adjustable polymer dispersed liquid crystal grating

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2024 Conference on Lasers and Electro-Optics, CLEO 2024

作者： Huang, Hsuan-Han Li, Yu-Jen Huang, Chiu-Chang Kuan, Chieh-Hsiung Graduate Institute of Electronics Engineering Department of Electrical Engineering National Taiwan University Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics Department of Electrical Engineering National Taiwan University Taiwan

The double-period grating structure is integrated in a polymer dispersed liquid crystal (PDLC) device and guides the arrangement of PDLC droplets. The grating period is changed by electronic control. CLEO 2024 © ... 详细信息

ISBN: (纸本)9781957171395

关键词： Electrooptical effects

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Adjustable polymer dispersed liquid crystal grating

Adjustable polymer dispersed liquid crystal grating

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CLEO: Science and Innovations in CLEO 2024, CLEO: S and I 2024 - Part of Conference on Lasers and Electro-Optics

关键词： Liquid crystals

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Smartphone-Integrated Reverse Lens Hemocount Microscope for Red Blood Cell Imaging

Smartphone-Integrated Reverse Lens Hemocount Microscope for ...

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2023 International Conference on Electrical engineering and Informatics, ICEEI 2023

作者： Izzrufi, Mochammad Izzrul Zakaria, Hasballah Bandung Institute of Technology Biomedical Engineering Study Program Bandung Indonesia

ISBN: (纸本)9798350381290

Anemia, a prevalent global medical condition affecting approximately 33% of the world's population in 2015 and 32% of Indonesian adolescents in 2018, is characterized by a reduction in red blood cell count or hemoglobin levels, resulting in diminished oxygen-carrying capacity within the bloodstream. The conventional method for detecting anemia involves Complete Blood Count (CBC), which demands specialized hematology analyzers and substantial time. In response to these constraints, the Hemocount, a portable microscope utilizing the reverse lens technique, was developed to capture high-quality images of red blood cells. This innovative approach requires blood sample standardization for optimal Hemocount performance. The technique involves inverting the mobile camera lens, aligning the sensor focus with the sample, while a preparation table and light source illuminate from below. Experiments with various lens, table, and light source configurations identified the optimal setup as employing the front camera lens from an iPhone 5s, a transparent table, and a cool white light source, yielding a digital image resolution of 42.19 nm/px. This resolution allows for blood cell detection within the size range of 165.92 px to 189.62 px. For optimal results when using Hemocount, a recommended blood concentration of 50% minimizes standard deviation, while concentrations of 30% maximize the correlation coefficient R, and 25% yield clear images by preventing red blood cell enlargement due to osmosis. © 2023 IEEE.

关键词： Light sources

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