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再生医学
Nanomaterials · 2018 ·Vol. 8 ·期 7 ·519 · IF 3.504

Applications of Nanosheets in Frontier Cellular Research

Wenjing Huang,Yuta Sunami,Hiroshi Kimura,Sheng Zhang

Several types of nanosheets, such as graphene oxide (GO) nanosheet, molybdenum disulfide (MoS2) and poly(l-lactic acid) (PLLA) nanosheets, have been developed and applied in vitro in cellular research over the past decade. Scientists have used nanosheet properties, such as ease of modification and flexibility, to develop new cell/protein sensing/imaging techniques and achieve regulation of specific cell functions. This review is divided into three main parts based on the application being examined: nanosheets as a substrate, nanosheets as a sensitive surface, and nanosheets in regenerative medicine. Furthermore, the applications of nanosheets are discussed, with two subsections in each section, based on their effects on cells and molecules. Finally, the application prospects of nanosheets in cellular research are summarized.Keywords:nanosheet;cell adhesion;drug delivery;cell capturing;regenerative medicine

CAS / MDL: 107-22-2
研究领域: 生物材料学 · 细胞生物学 · 医学工程
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Materials Today Bio · 2024 · IF 8.7

Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks

Zhonglian Wu,Hang Yao,Haidi Sun,Zehao Gu,Xu Hu,Jian Yang,Junli Shi,Haojun Yang,Jihang Dai,Hui Chong,Dong-An Wang,Liwei Lin,Wang Zhang

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

研究领域: 生物材料学 · 组织工程学 · 再生医学
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PHARMACOLOGICAL RESEARCH · 2024 · IF 9.1

Far-infrared radiation and its therapeutic parameters: A superior alternative for future regenerative medicine?

Bo Qin,Shi-jie Fu,Xiong-fei Xu,Jiu-jie Yang,Yuping Wang,Lin-na Wang,Bai-xiong Huang,Jing Zhong,Wan-yu Wu,Heng-ao Lu,Betty Yuen Kwan Law,Nick Wang,Io Nam Wong,Vincent Kam Wai Wong

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

研究领域: 医学 · 生物学 · 光学疗法
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Peptide-Grafted Microspheres for Mesenchymal Stem Cell Sorting and Expansion by Selective Adhesion

Wu Shuo,Wang Zongliang,Wang Yu,Guo Min,Zhou Mengyang,Wang Liqiang,Ma Jie,Zhang Peibiao

Mesenchymal stem cells (MSCs) have considerable value in regenerative medicine because of their unique properties such as pluripotency, self-renewal ability, and low immunogenicity. Isolation and purification are prerequisites for various biomedical applications of MSCs, and traditional sorting methods are often expensive, complicated, and difficult to apply on a large scale. In addition to purification, the requirement for expansion of cells also limits the further application of MSCs. The purpose of this study was to develop a unique magnetic sorting microsphere to obtain relatively pure and high-yield MSCs in an economical and effective way, that can also be used for the expansion of MSCs. Poly (ethylene glycol) (PEG)-based anti-adhesive treatment of the prepared oleic acid grafted Fe3O4-poly (lactic-co-glycolic acid) magnetic microspheres was performed, and then E7 peptide was covalently grafted onto the treated microspheres. Upon a series of characterization, the magnetic microspheres were of uniform size, and cells were unable to adhere to the PEG-treated surface. E7 grafting significantly improved cell adhesion and proliferation. The results obtained from separate culture of various cell types as well as static or dynamic co-culture showed that selective adhesion of MSCs was observed on the magnetic sorting microspheres. Furthermore, the cells expanded on the microspheres maintained their phenotype and typical differentiation potentials. The magnetic properties of the microspheres enabled sampling, distribution, and transfer of cells without the usage of trypsin digestion. And it facilitated the separation of cells and microspheres for harvesting of MSCs after digestion. These findings have promising prospects for MSC research and clinical applications.

研究领域: 再生医学 · 干细胞生物学 · 生物医学工程
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2023 · IF 3.6

Study on galactosylated sodium alginate for enhancing HepG2 Cells adhesion and 3D printability

Chunyang Zhang,Xiaochang Lu,Cuiting Lian,Xiongya Li,Hao Liu,Longge Hu,Ranjith Kumar Kankala,Aizheng Chen,Shibin Wang,Chaoping Fu

Sodium alginate is a polyanionic natural polysaccharide polymer widely used in tissue engineering. However, the lack of binding domains for interaction with cells limits its application in regenerative medicine. This study designed a kind of galactosylated sodium alginate (G-SA) material with improved galactose grafting rate by EDC/NHS activation of carboxyl groups in MES buffer and subsequently cross-linking by Ca2+ aims to enhance the adherence behavior of HepG2 cells on alginate substrate. The synthesized G-SA was characterized by Fourier transform infrared spectra and nuclear magnetic resonance spectroscopy. G-SA exhibited good biocompatibility and significantly enhanced the adhesion behavior of HepG2 cells on its surface. Furthermore, we demonstrated that the effect of G-SA concentration in enhancing cell adhesion was diminished at higher than 2% w/v. Finally, the suitability of G-SA material is investigated for 3D printing, demonstrating that HepG2 cells could maintain high viability and excellent printability in the interior of the gel. In addition, cells could multiply and grow into cell spheroids with an average size of 200 μm in G-SA scaffolds. These results indicated that galactosylated sodium alginate material could be used as a 3D culture system that could be effective for engineering liver cancer models.

研究领域: 组织工程 · 再生医学 · 生物医学工程 · 细胞生物学
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CELL BIOLOGY INTERNATIONAL · 2023 · IF 3.9

Decoding the multifaceted signatures and transcriptomic characteristics of stem cells derived from apical papilla and dental pulp of human supernumerary teeth

Juan Ning,Leisheng Zhang,Hanjing Xie,Lian Chai,Jun Yao

Supernumerary teeth are advantaged sources for high-quality stem cell preparation from both apical papilla (SCAP-Ss) and dental pulp (DPSCs). However, the deficiency of the systematic and detailed comparison of the biological and transcriptomic characteristics of the aforementioned stem cells largely hinders their application in regenerative medicine. Herein, we collected supernumerary teeth for SCAP-S and DPSC isolation and identification by utilizing multiple biological tests (e.g., growth curve, cell cycle and apoptosis, adipogenic and osteogenic differentiation, and quantitative real-time polymerase chain reaction). Furthermore, we took advantage of transcriptome sequencing and multifaceted bioinformatic analyses to dissect the similarities and diversities between them. In this study, we found that SCAP-Ss and DPSCs showed indistinctive signatures in morphology and immunophenotypes, whereas with diversity in cell vitality and multi-lineage differentiation as well as gene expression profiling and differentially expressed genes-associated gene ontology and signaling pathways. Collectively, our data indicated the diversity of the multifaceted signatures of human supernumerary teeth-derived stem cells both at the cellular and molecular levels, which also supplied new references for SCAP-Ss serving as splendid alternative stem cell sources for regenerative medicine purposes.

CAS / MDL: 64-17-5
研究领域: 口腔医学 · 干细胞研究 · 生物信息学
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Bioactive Materials · 2024 · IF 18

3D bioprinting of high-performance hydrogel with in-situ birth of stem cell spheroids

Shunyao Zhu,Xueyuan Liao,Yue Xu,Nazi Zhou,Yingzi Pan,Jinlin Song,Taijing Zheng,Lin Zhang,Liyun Bai,Yu Wang,Xia Zhou,Maling Gou,Jie Tao,Rui Liu

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo . The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

研究领域: 生物医学工程 · 组织工程 · 再生医学 · 材料科学
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MATERIALS & DESIGN · 2023 · IF 8.4

Development of an integrated device utilizing exosome-hyaluronic acid-based hydrogel and investigation of its osteogenic and angiogenic characteristics

Longbiao Wan,Yan He,Ao Wang,Jiali Pan,Chun Xu,Dehao Fu,Qingsong Ye,Fei Wu

Tissue engineering (TE) has been widely proposed as a potential solution to the global shortage of donor organs for transplantation. Organic and biocompatible materials have been explored as potential candidates to mimic natural extracellular matrices for regenerative applications. Biomimetic environments have been created using these materials, and hydrogels have shown promise in tissue regeneration due to their rapid gel-forming ability and excellent biocompatibility. Therefore, achieving comparisons between studies utilizing identical materials can prove arduous, as variations in material concentrations, sample preparation techniques, and laboratory conditions significantly influence the physicochemical characteristics of hydrogel systems. To ensure their promotion for clinical purposes, stable variables are crucial. In this regard, we have created an amalgamated and simplified device to assist in hydrogel-based systems using hyaluronic acid and alginate-loaded exosomes for regenerative medicine. The objective of this study is to examine the porosity, injectability, release of loaded exosomes, mechanical properties, and the rate of dissolution and degradation of well-known biomaterials, including alginate and hyaluronic acid, at different concentrations in a stable and controlled setting provided by a simplified integrated device. Furthermore, it aims to comprehensively assess their ex vivo and in vivo osteogenesis and vascularity-related metrics.

CAS / MDL: 1071-93-8 7647-01-0
研究领域: 生物材料科学 · 组织工程 · 再生医学 · 生物医学工程
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2020 · IF 2.69

Hydrosoluble collagen based biodegradable hybrid hydrogel for biomedical scaffold

Qian Ji,Hao Zhang,Xihe Zhang,Qiaoqiao Ma,Liping Teng,Lipeng Qiu

Hydrogel scaffolds are explored as efficient methods to repair damaged organs or tissues. In this study, we developed a hybrid hydrogel system based on collagen (Col) and PEG-derived polymer (PEGF) for biomedical scaffold. The Col-PEGF hybrid hydrogel, in which different materials were combined and sequential interpenetrating networks were built, achieved significantly enhanced mechanical strength and viscoelasticity compared with the corresponding Col hydrogel or PEGF hydrogel. Degradation test indicated that Col enabled the hybrid hydrogel to be broken down via enzymatic degradation while PEGF contributed to the anti-degradation of the hydrogel. This balanced biodegradability of Col-PEGF hydrogel would be advantageous to the application for tissue engineering and regenerative medicine. Moreover, the Col-PEGF hybrid hydrogel with micron-sized pores and variable moisture performed good biocompatibility to NIH-3T3 cells, and supplied a favorable environment for cell growth and proliferation. Therefore, the Col-PEGF hydrogel will provide a promising biomedical scaffold for the therapy of tissue defects.

研究领域: 生物材料 · 生物医学工程 · 组织工程
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ACS Nano · 2025 · IF 16

Bioactive Decellularized Extracellular Matrix Platform Integrating Multifunctional Nanozymes and Cell-Laden Microgels for Acute Liver Failure Treatment

Xiaodie Chen,Jiabin Zhang,Tong Lin,Feng Zhou,Fenfang Li,Tiantian Xue,Qingguo Zhong,Weijen Lee,Guipan Chen,Haixia Wang,Enguo Ju,Mingqiang Li,Yu Tao

Mesenchymal stem cell (MSC) therapy has emerged as a promising alternative approach for treating acute liver failure (ALF) while confronting the shortage of low efficiency and poor engraftment within a hostile liver milieu. In this study, we establish a bioactive decellularized extracellular matrix (dECM) platform that incorporates dihydrolipoic acid (DHLA)-protected Pt nanoclusters doped with Cu (PtCu-DHLA) nanozymes and cell-laden microgels. The PtCu-DHLA nanozymes, selected for their versatility, function as antioxidant, anti-inflammatory, pro-proliferative, and pro-angiogenic agents, enhancing ALF alleviation and providing an optimal microenvironment for MSC transplantation. Additionally, a methacrylic anhydride (MA)-modified porcine liver-derived decellularized extracellular matrix (PLdECM) hydrogel (PLdECMMA) has been developed for the construction of microgels via microfluidic devices. Interferon γ (IFNγ) preconditioned MSCs encapsulated in PLdECMMA microgels exhibit enhanced immunomodulating activity and prolonged survival. PtCu-DHLA nanozymes and cell-laden microgels are codelivered by leveraging the PLdECM hydrogel for orthotopic transplantation. The transplanted dECM platform enables an efficient and successful rescue of CCl4-induced ALF by counteracting oxidative stress, suppressing inflammatory storms, and promoting cellular regeneration. Overall, this study highlights a synergistic and reinforced strategy that combines biomimetic nanozymes with MSC therapy, offering significant potential for ALF treatment and broader applications in regenerative medicine.

研究领域: 肝病学 · 干细胞研究 · 纳米医学 · 再生医学
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Polymers · 2020 ·Vol. 12 ·期 5 ·1138 · IF 3.426

Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process

Lixuan Wang,Shiyan Dong,Yutong Liu,Yifan Ma,Jingjing Zhang,Zhaogang Yang,Wen Jiang,Yuan Yuan

Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO2bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics.Keywords:injectable hydrogel;porous structure;in-situ bubble-forming hydrogel entrapment

研究领域: 材料科学 · 生物医学工程 · 再生医学 · 组织工程
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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
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