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Small · 2025 · IF 12.1

High-Resolution Imaging of Biological Soft and Hard Tissues Using NIR Scintillators

Xinran Wang,Heng Dai,Yichun Liu,Linglu Kuang,Hao Song,Zhaowei Teng,Dawei Wang,Ting Wang,Xuhui Xu

Near-infrared (NIR) luminescence has emerged as a powerful tool in biological imaging due to its nondestructive nature, high spatiotemporal resolution, and deep tissue penetration. However, traditional NIR imaging often fails to provide detailed information about hard tissues such as bones. In this study, an approach for simultaneous imaging of soft and hard tissues using Lu 1.5 Mg 1.5 Al 3.5 Si 1.5 O 12 : Yb 3+ as an NIR scintillator is presented. Under X-ray irradiation, Lu 1.5 Mg 1.5 Al 3.5 Si 1.5 O 12 : Yb 3+ scintillator emits NIR emission with a peak at 970 nm with thermal quenching resistance, which is strongly absorbed by soft tissues, enabling soft tissue imaging. Additionally, the scintillator provides a high signal-to-noise ratio for X-ray imaging, allowing for high-resolution imaging of hard tissues, unaffected by ambient light, with a spatial resolution of up to 203 µm. By leveraging X-ray as the sole excitation source, this method provides a comprehensive view of internal biological structures, including vascular and skeletal tissues, with high resolution and minimal interference. This innovation holds great promise for advancing medical imaging technologies and enhancing diagnostic capabilities.

研究领域: 医学影像学 · 生物物理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 8 ·3569 · IF 4.9

An Improved SHANEL Procedure for Clearing and Staining Brain Tissue from Multiple Species

Fu Zeng,Lian Huang,Ding Han,Renjie Liu,Kongjia Zhang,Yuwen Su,Tong Su,Yarong Lin,Jianbo Xiu

Recent advances in tissue clearing chemistry have revolutionized three-dimensional imaging by enabling whole-organ antibody labeling, even in thick human tissue samples. However, these techniques face limitations, including reduced clearance efficiency in thick tissue blocks, prolonged processing times, and other challenges specific to formalin-fixed human brain tissue, such as autofluorescence due to the presence of lipofuscin, neuromelanin pigments, and residual blood. To address these challenges, we have developed an improved SHANEL procedure, iSHANEL, which is compatible with brain tissue from multiple species, including nonrodents. iSHANEL significantly enhances the tissue transparency. It effectively removes lipids, particularly sphingolipids, from brain tissue across different species. For brain vasculature imaging, it offers the better visualization of vascular structures at high magnification, reducing light scattering and background noise. Moreover, iSHANEL can be effectively applied to large tissue from pigs and cynomolgus monkeys, and it preserves protein immunogenicity well, as evidenced by immunostaining with the microglia-specific marker IBA-1. We also investigated methods to reduce blood vessel autofluorescence. Overall, iSHANEL provides an improved procedure for the high-resolution 3D imaging of brain tissue across multiple species.

研究领域: 神经科学 · 生物化学 · 显微成像
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Scientific Reports · 2025 ·Vol. 15 ·期 1 ·1-12 · IF 3.9

Application of HEMA-AAm copolymer to achieve faster optical tissue transparency for 2D/3D fluorescence imaging

Ma Hui,Qin Ruixiu,Yao Qiufeng,Li Yier,Cong Xingshun,Wu Wenhui,Zhao Qi,Ye Hua,Wu Kefeng

Optical transparency methods can facilitate biological tissue optical imaging, which enabled accurate three-dimensional (3D) signal visualization and quantification of complex biological structures. Unfortunately, existing optical clearing approaches present a compromise between maximizing clearing capability, the preservation of fluorescent protein emission and the speed of sample processing. To address this challenge, we synthesis of a 2-hydroxyethyl methacrylate (HEMA)-acrylamide (AAm) copolymer using antipyrine (ATP) and 2,2′-thiodiethanol (TDE) as solvent, which could embed tissue samples rapidly and highly transparent, and compatible with multiple fluorescence labeling. It can enable volumetric imaging of tissue up to the scale of mice organs, shrinkage duration of the clearing and preserve emission from fluorescent proteins and dyes. This copolymer with suitable toughness and plasticity allows the tissue of interest to be sectioned into thin slices, and histological techniques provide high-resolution two-dimensional (2D) images of cells and subcellular structures. Furthermore, HEMA-AAm copolymer -tissue transparent could distinguish cell structures between healthy and diabetic disease in dye-labeled liver tissues, which provides new insights into pathological diagnosis and analysis. Copolymer provides an environment to facilitate high-resolution 3D/2D fluorescence imaging, which enables the study of cellular and tissue morphology in experimental and clinical conditions of interest.

CAS / MDL: 868-77-9
研究领域: 生物医学工程 · 荧光成像 · 组织光学 · 病理诊断
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ACS Omega · 2025 · IF 4.3

Mechanical Behavior and Indentation-Induced Injury of Soft Microtissues with Different Densification Levels

Wenjuan Zhu,Xiaoning Han,Linhong Deng,Xiang Wang

Tissue densification is a fundamental biological process involved in development, regeneration, and disease, significantly influencing tissue mechanics and cellular mechanical microenvironments. However, the effects of tissue densification on mechanical properties, the roles of key cytoskeletal components, and their responses to external mechanical stress remain poorly understood. In this study, fibroblast–collagen microtissues were cultured on polydimethylsiloxane (PDMS) microstring scaffolds with different mechanical constraints to generate low- and high-densification microtissues. High-precision indentation force sensor analysis demonstrated that increased densification enhanced microtissue stiffness, accelerated stress relaxation, and elevated energy dissipation. Pharmacological disruption of cytoskeletons revealed the critical role of F-actin in regulating stiffness and viscoelastic resistance in a densification-dependent manner: in high-densification microtissues, F-actin had a greater impact on stiffness and dissipated energy, but a reduced effect on stress relaxation. Furthermore, under 50% strain indentation, high-densification microtissues exhibited irreversible deformation and increased cellular injury. Injured regions showed reduced stiffness, shorter stress relaxation time constants, and higher energy dissipation, indicating structural and cellular damage. These results enhance our understanding of tissue mechanobiology by elucidating the interplay between tissue densification, cytoskeletal mechanics, and injury responses, providing valuable insights for optimizing tissue mechanical microenvironments and improving the mechanical compatibility of biomaterials.

CAS / MDL: 9002-89-5
研究领域: 生物力学 · 细胞生物学 · 再生医学
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE · 2022 ·Vol. 33 ·期 10 ·1-13 · IF 4.727

Biological small-calibre tissue engineered blood vessels developed by electrospinning and in-body tissue architecture

Su Zhixiang,Xing Yuehao,Wang Fei,Xu Zeqin,Gu Yongquan

There are no suitable methods to develop the small-calibre tissue-engineered blood vessels (TEBVs) that can be widely used in the clinic. In this study, we developed a new method that combines electrospinning and in-body tissue architecture(iBTA) to develop small-calibre TEBVs. Electrospinning imparted mechanical properties to the TEBVs, and the iBTA imparted biological properties to the TEBVs. The hybrid fibres of PLCL (poly(L-lactic-co-ε-caprolactone) and PU (Polyurethane) were obtained by electrospinning, and the fibre scaffolds were then implanted subcutaneously in the abdominal area of the rabbit (as an in vivo bioreactor). The biotubes were harvested after four weeks. The mechanical properties of the biotubes were most similar to those of the native rabbit aorta. Biotubes and the PLCL/PU vascular scaffolds were implanted into the rabbit carotid artery. The biotube exhibited a better patency rate and certain remodelling ability in the rabbit model, which indicated the potential use of this hybridization method to develop small-calibre TEBVs. Sketch map of developing the biotube. The vascular scaffolds were prepared by electrospinning (A). Silicone tube was used as the core, and the vascular scaffold was used as the shell (B). The vascular scaffold and silicone tube were implanted subcutaneously in the abdominal area of the rabbit (C). The biotube was extruded from the silicone tube after 4 weeks ofembedding (D). The biotube was implanted for the rabbit carotid artery (E).

研究领域: 组织工程 · 生物材料 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Bio Materials · 2019 · IF 0

Strong and Degradable Adhesion of Hydrogels

Hang Yang,Chenghai Li,Jingda Tang,Zhigang Suo

Adhesives potentially offer convenient means to close wounds, but existing adhesives do not fulfill many common requirements. Here we demonstrate an approach to develop hydrogel adhesives that are strong initially, remain soft when adhered to soft tissues, and degrade over time. We demonstrate the approach by using a hydrogel that dissipates a large amount of energy during separation, forms strong and interlinks with the soft tissues, and degrades by breaking cross-links. The hydrogel achieves initial adhesion energies of 300–700 J/m2 when adhered to different tissues, can bear huge pressure, and completely degrades in 5 weeks under simulated physiological conditions.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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Materials Today Bio · 2025 · IF 10.2

Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging

Wenyi Hou,Zhaoyi Lin,Xinling Chen,Yu Sun,Yao Lin,Mengran Peng,Feng Zhou,Huamin Jiang,Yan Li,Yue Zheng

There have been various interventions for photoaging skin, such as retinoic acid treatment and laser therapy. However, more precise, secure, and effective technologies and materials were still need to be explored. Cathepsin D (CTSD) repairs the epidermal barrier in chronic photodamaged skin through increasing TGase-1 expression and activity. Cathepsin K (CTSK) affects the metabolism of skin elastic fibers. Therefore, gelatin/alginate composite hydrogel microspheres loaded with CTSD or CTSK were fabricated. The microspheres with an average size of 79.8 ± 30.4 μm were stable in PBS (pH 7.4) for 5 days and then disintegrated in vitro . 0.1 mg/mL of microspheres continuously released 12-13 ng/mL CTSD or CTSK for the first three consecutive days. In vivo , the microspheres were almost completed degraded on day 7 after the subcutaneous injection. The biosafety and efficacy of CTSD- and CTSK- microspheres were confirmed in vitro and in vivo . They reduced ROS and inhibited the degradation of skin collagen and elastic fibers by upregulating Nrf2 and downregulating MMP-1 and MMP-3, which reversed photodamage of skin induced by UV. In conclusion, the gelatin/alginate composite microspheres loaded with CTSD or CTSK showed a great potential for chronic photodamaged skin.

CAS / MDL: 9005-38-3
研究领域: 生物医学工程 · 皮肤科学 · 药剂学 · 生物材料 · 再生医学
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VIEW · 2025 · IF 8.5

Chemical dehydration-induced ultrafast clearing method for human tissues

Yi Dai,Jianyi Xu,Jie Hao,Zhang Liu,Chengze Lan,Guanghua Xu,Xizhi Meng,Yating Deng,Peng Wan,Kunxing Liu,Yingtao Yao,Fang Zhao,Peng Fei,Xiu Nie,Gang Lv,Dan Zhu,Tingting Yu

Three-dimensional (3D) visualization and analysis of histological features in human tissue can enhance our comprehension of organ function and elevate the precision of clinical diagnosis. Tissue optical clearing technique has emerged as a potent approach for achieving 3D imaging of large human tissues at a cellular resolution. However, the utilization of tissue clearing to obtain 3D structures of human tissue is hindered by prolonged incubation periods and intricate procedural steps. To address these issues, a rapid and straightforward clearing protocol termed single-step dehydration solvent-based clearing (SSD) is proposed by the introduction of trimethyl borate, which is innovatively incorporated into the tissue clearing process to expedite incubation and streamline the clearing procedure via chemical dehydration. This method reduces the clearing time by 70% and exhibits ideal compatibility with a variety of probes. SSD allows 3D histological imaging and analysis of nerves and vessels, as well as 3D pathological assessment of tumors, within human organs. As an ultrafast clearing alternative, SSD promises to facilitate histological research and enhance clinical diagnostic capabilities.

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Military Medical Research · 2023 ·Vol. 10 ·期 1 ·1-15 · IF 21.1

Adhesive cryogel particles for bridging confined and irregular tissue defects

Xue Yao-Ting,Chen Ming-Yu,Cao Jia-Sheng,Wang Lei,Hu Jia-Hao,Li Si-Yang,Shen Ji-Liang,Li Xin-Ge,Zhang Kai-Hang,Hao Shu-Qiang,Juengpanich Sarun,Cheng Si-Bo,Wong Tuck-Whye,Yang Xu-Xu,Li Tie-Feng,Cai Xiu-Jun,Yang Wei

Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging.Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery.Results ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface.Conclusion sACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

研究领域: 生物医学工程 · 组织工程 · 外科材料 · 伤口愈合 · 生物材料
✓ 已验证 DOI PubMed 高影响因子
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Plants-Basel · 2023 ·Vol. 13 ·期 1 ·10 · IF 4.5

Regenerating Saffron (Crocus sativus L.) from Corm Lateral Buds via Indirect Somatic Embryogenesis

Yangyang Ma,Yiyu Pan,Bizeng Mao

Saffron (Crocus sativusL.), being one of the distinguished commercial spice crops in the world, is in demand for its culinary, colorant, and pharmaceutical benefits. In this study, a novel indirect somatic embryogenesis (SE) system was, thus, established for the study of this plant. To this end, firstly, the lateral buds were cultured. Then, the cultures were transformed using Murashige and Skoog (MS) medium supplemented with either 6-benzyladenine (BA: 5 and 10 mg/L), naphthalene acetic acid (NAA: 0, 1, and 2 mg/L), or trans-zeatin (tZ: 0, 0.5, and 1.0 mg/L), before being classified into four structures: white globular (WG), yellow compact nodular (YCN), yellow-brown fragile (YBF), and dark-brown porous (DBP). As soon as BA (10 mg/L) and NAA (2 mg/L) were added, elevated percentages of white globular calli (56.8%) and white globular calli (31.5%) structures were induced. Additionally, 6-benzyladenine (5 mg/L) and naphthalene acetic acid (1 mg/L) allowed the formation of yellow-brown fragile structures, and the combination of 6-benzyladenine (10 mg/L) with trans-zeatin (1 mg/L) formed the DBP structures. After three months, the white globular calli were incubated using the MS basal medium, before being augmented with thidiazuron (TDZ: 1 mg/L) and picloram (PIC: 2 mg/L), from which 60% of the cases matured into shoots and, ultimately, cormlets. Morphoanatomical analyses also showed that the white globular calli cells were closely arranged, as they had a dense cytoplasm, a significant vascular differentiation, and embryoids. Furthermore, the yellow compact nodular structures were characterized by a strong differentiation capacity and contained many meristematic cells with high caryomitosis centers. We observed that the yellow-brown fragile calli had looser cell arrangements, with a vascular structure located on the protoderm edge, while there was no obvious cellular arrangement in the dark-brown porous structures. The induction of the adventitious buds in vivo on the MS medium that was supplemented with thidiazuron and picloram accordingly demonstrated the highest rates (60%) of white globular calli.Keywords:Crocus sativus;differentiation;morpho-histological;somatic embryogenesis

研究领域: 植物生物技术 · 植物组织培养 · 植物激素 · 形态学与组织学
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Regenerative Biomaterials · 2024 · IF 5.6

Microvascular network based on the hilbert curve for nutrient transport in thick tissue

Wang Zhenxing,Liu Xuemin,Shi Xuetao,Wang Yingjun

To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models in vitro. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to in vitro thick tissue block models. This provides a robust foundation for future in vitro research and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.

研究领域: 组织工程 · 再生医学 · 生物医学研究 · 生物打印
✓ 已验证 DOI 高影响因子
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Nano Life · 2021 · IF 0

4D Printing of Self-Folding Hydrogel Tubes for Potential Tissue Engineering Applications

Yu-Dong Zhao,Jia-Hui Lai,Min Wang

In recent years, 4D printing has gained increasing attention in the tissue engineering field since this advanced manufacturing platform can create stimulus-responsive structures, which can change their shapes, functions, and/or properties when appropriate external stimulus/stimuli is/are applied. A number of hydrogels with swellable/shrinkable abilities have been explored for 4D printing to fabricate different shape-morphing structures for tissue engineering. Among them, gelatin methacryloyl (GelMA) has been 4D printed, which can self-fold into microtubular structures. Currently, the self-folding ability of 4D printed GelMA hydrogels is mainly based on the different cross-linking degrees (which control and govern the swelling degrees) across the thickness of hydrogels. However, this strategy alone can only form self-folding GelMA tubes with diameters at the micrometer level and cannot create self-folding GelMA tubes with diameters at the millimeter level, which is mainly due to the insufficient internal force generated in 4D printed GelMA hydrogels when they are exposed to water. To overcome this limitation, this study has investigated a new strategy to fabricate self-folding GelMA tubes with large diameters at the millimeter level for tissue engineering applications. The new strategy introduced a cross-linking degree gradient across the GelMA plane in addition to its thickness by printing a second layer of strips on the first 4D printed GelMA film. In the aqueous environment, under the current fabrication condition, such bilayer GelMA hydrogels could self-fold into tubes of larger diameters up to 6 mm. The in vitro release behavior of heparin incorporated into the 4D printed GelMA was also studied. It was shown that heparin release could be controlled by the GelMA concentration and heparin content in 4D printed GelMA. The 4D printed GelMA hydrogels with the improved self-folding ability and controlled release of a drug are promising for targeted tissue engineering applications.

研究领域: 生物医学工程 · 材料科学 · 组织工程
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