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Nanomedicine-Nanotechnology Biology and Medicine · 2023 · IF 5.4

Fabrication of blended nanofibrous cardiac patch transplanted with TGF-β3 and human umbilical cord MSCs-derived exosomes for potential cardiac regeneration after acute myocardial infarction

Ping Ping,Shasha Guan,Chaoxue Ning,Ting Yang,Yali Zhao,Pei Zhang,Zhitao Gao,Shihui Fu

Acute myocardial infarction (AMI) is a common cardiovascular condition that progressively results in heart failure. In the present study, we have designed to load transforming growth factor beta 3 (TGF-β3) and cardio potential exosomes into the blended polycaprolactone/type I collagen (PCL/COL-1) nanofibrous patch (Exo@TGF-β3@NFs) and examined its feasibility for cardiac repair . The bioactivity of the developed NFs towards the migration and proliferation of human umbilical vein endothelial cells was determined using in vitro cell compatibility assays. Additionally, Exo@TGF-β3/NFs showed up-regulation of genes involved in angiogenesis and mesenchymal differentiations in vitro . The in vivo experiments performed 4 weeks after transplantation showed that the Exo@TGF-β3@NFs had a higher LV ejection fraction and fraction shortening functions. Subsequently, it has been determined that Exo@TGF-β3@NFs significantly reduced AMI size and fibrosis and increased scar thickness. The developed NFs approach will become a useful therapeutic approach for the treatment of AMI.

研究领域: 生物医学工程 · 心血管病学 · 再生医学
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ADVANCED MATERIALS · 2021 ·Vol. 33 ·期 41 ·2102926 · IF 30.849

An Engineered Pseudo-Macrophage for Rapid Treatment of Bacteria-Infected Osteomyelitis via Microwave-Excited Anti-Infection and Immunoregulation

Jieni Fu,Yuan Li,Yu Zhang,Yanqin Liang,Yufeng Zheng,Zhaoyang Li,Shengli Zhu,Changyi Li,Zhenduo Cui,Shuilin Wu

Preventing deep bacterial infection and simultaneously enhancing osteogenic differentiation are in great demand for osteomyelitis. Microwave (MW) dynamic therapy is attracting attention due to its excellent penetration ability, but the mechanism of MW-induced reactive oxygen species (ROS) is still unknown. Herein, MW-responsive engineered pseudo-macrophages (M-Fe 3 O 4 /Au nanoparticles (NPs)) are fabricated to clear Staphylococcus aureus infections and induce M2 polarization of macrophages to improve osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) under MW irradiation. Fe 3 O 4 /Au NPs can generate · O 2 − and heat under MW irradiation in a saline solution, and the mechanism is put forward via finite element modeling and density functional theory calculations. Due to the gap plasmon, electromagnetic hotspots are produced at Fe 3 O 4 –Au interface at 2.45 GHz. Because of these induced electromagnetic hotspots, the sodium species is field-ionized and subsequently reacts with oxygen to produce · O 2 − . Meanwhile, the Fe 3 O 4 /Au NPs have a stronger ability than Fe 3 O 4 NPs to fix oxygen, favoring the production of ROS. Additionally, MW-treated macrophages diminish to secrete inflammatory cytokines, resulting in the decrease of ROS production in MSCs and thus enhancing their osteogenic differentiation. These engineered pseudo-macrophages will be promising for effectively treating bacterial infections and promoting osteoblast differentiation simultaneously in deep tissues under MW irradiation.

研究领域: 生物医学工程 · 纳米技术 · 传染病 · 组织工程 · 免疫学
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ACS Nano · 2023 · IF 17.1

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration

Xiaodi Zhang,Qi Li,Longfei Li,Jiang Ouyang,Tong Wang,Junjie Chen,Xiaoqing Hu,Yingfang Ao,Duotian Qin,Liqun Zhang,Jiajia Xue,Jin Cheng,Wei Tao

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

CAS / MDL: 98-10-2 75-09-2 75-89-8
研究领域: 组织工程 · 生物材料 · 生物医学工程 · 再生医学
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Applied Materials Today · 2020 · IF 8.352

Improved osteointegration by SEW2871-encapsulated multilayers on micro-structured titanium via macrophages recruitment and immunomodulation

Ye He,Kun Xu,Ke Li,Zhang Yuan,Yao Ding,Maowen Chen,Chuanchuan Lin,Bailong Tao,Xuemin Li,Guanjun Zhang,Peng Liu,Kaiyong Cai

The main task for medical-used titanium researches is to improve the in vivo osteointegration. In addition to mesenchymal stromal cells (MSCs)-osteoblasts lineage, macrophages also undertake irreplaceable roles in the osteointegration process of a titanium implant. The timely recruitment and efficient immunomodulation of macrophages is important. In this work, to firstly endow macrophages recruitment ability and immunomodulation effects to titanium, we fabricated a micro-structured titanium via a double acid etching method. Then a gelatin-chitosan multilayer contained SEW2871 (a macrophage recruitment agent) was constructed on the micro-structured titanium by a layer-by-layer (LBL) self-assembly technique. According to our results, the prepared samples effectively induced macrophages migration when SEW2871 was slowly released . The anti-inflammatory response of macrophages was enhanced and the pro-inflammatory response was alleviated, which were attributed to the changed surface roughness and wettability. This immunomodulation effects of macrophages further improved the osteogenic differentiation of MSCs in vitro and obtained a better osteointegration in vivo after 6 weeks of implantation. Therefore, this study demonstrated that a favorable osteointegration of titanium materials could also be achieved by regulating macrophages recruitment and immunomodulation, which implying a potential strategy for titanium implants amelioration.

CAS / MDL: 130-22-3
研究领域: 生物材料 · 组织工程 · 免疫学 · 骨科
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Stem Cells International · 2024 ·Vol. 2024 ·期 1 ·7419270 · IF 3.8

Comparative Analysis of the Therapeutic Effects of MSCs From Umbilical Cord, Bone Marrow, and Adipose Tissue and Investigating the Impact of Oxidized RNA on Radiation-Induced Lung Injury

Rui Zhai,Fumin Tai,Kexin Ding,Xin Tan,Hujie Li,Zhengyue Cao,Changhui Ge,Xiaofei Zheng,Hanjiang Fu

Radiation-induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose-derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation-induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti-inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation-induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8-hydroyguanosine (8-OHG) content indicated that MSCs possess reparative properties against radiation-induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC-based treatment for RILI.

CAS / MDL: 54827-17-7
研究领域: 肿瘤学 · 干细胞生物学 · 放射生物学 · 肺科学 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Biphasic CK2.1-coated β-glycerophosphate chitosan/LL37-modified layered double hydroxide chitosan composite scaffolds enhance coordinated hyaline cartilage and subchondral bone regeneration

Pei Liu,Mengna Li,Hongping Yu,Haoyu Fang,Junhui Yin,Daoyu Zhu,Qianhao Yang,Qinfei Ke,Yigang Huang,Yaping Guo,Youshui Gao,Changqing Zhang

Articular osteochondral defect is commonly seen after trauma or in patients with degenerative osteoarthritis. Currently, the treatment of osteochondral lesions is still challenging due to the limited healing ability of cartilage as well as the poorly effective traditional method. In this study, we fabricated a bilayer peptide-loaded scaffold consisting of CK2.1 coated β-glycerophosphate/chitosan ( [email protected] ) for cartilage regeneration and LL37 modified layered double hydroxide/chitosan ( [email protected] ) for subchondral bone regeneration, designed in an integrated strategy involving mesenchymal stem cells (MSCs) recruitment and multifunctional therapeutic biomaterials of bone regeneration and vascularization. The lower LC scaffold is highlighted with a biomimetic lamellar structural design, providing a novel platform for the integration of newborn bone tissue and blood vessels. In vitro results showed our peptide-loaded bilayer scaffold could induce the MSCs to differentiate into chondrocytes and osteoblasts in different layers respectively. [email protected] could also attract MSCs and promote vasculogenesis in vitro. Meanwhile, osteochondral defect could be efficiently repaired by this peptide-modified bilayered scaffold in the rabbit model. This study demonstrated that our composite scaffold could smartly enhance the repair of hyaline cartilage and subchondral bone defect, which shed light on a novel therapeutic strategy for the intervention of patients with articular osteochondral defect.

CAS / MDL: 9004-62-0
研究领域: 组织工程 · 再生医学 · 生物材料科学 · 骨科
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Continuous-Gradient Mineralized Hydrogel Synthesized via Gravitational Osmosis for Osteochondral Defect Repair

Rongtai Sun,Qiang Zhang,Congcong Yu,Yiwei Zhu,Yang Zheng,Tianyuan Gu,Lin Ye,Wentao Yang,Xiaozhang Ying,Yiyang Xu,Shunwu Fan,Ruikang Tang,Weiming Qi,Shasha Yao

The repair of hierarchical osteochondral defects requires complex gradient reconstruction at different levels, with continuous-gradient mineralization being crucial. Strategies for achieving continuous-gradient mineralization have rarely been reported. Here, a continuous-gradient mineralized hydrogel is prepared using simple gravitational osmosis of a ≈2 nm amorphous calcium phosphate nanocluster (ACPC) suspension into composite organic frameworks for osteochondral regeneration. During gravitational infiltration, ACPC underwent gradual mineralization, resulting in the spontaneous formation of hydroxyapatite (HAP). The continuous-gradient mineralized hydrogel aligned closely with the normal osteochondral structure, thereby effectively promoting repair of the cartilage and subchondral bone. In the cartilage layer, organic compounds improved the oxidative stress environment induced by injury and complemented the extracellular matrix of the cartilage. In the subchondral bone layer, HAP from the continuously mineralized hydrogel induced intracellular calcium accumulation in mesenchymal stem cells (MSCs), activating calcium/calmodulin-dependent protein kinase 2 (CaMK2) and promoting osteogenic differentiation of MSCs through the calcium signaling pathway. Ultimately, compared with the nongradient hydrogel, this innovative gradient mineralization method exhibited significantly enhanced regeneration capabilities for osteochondral defects, as evidenced by metrics, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). This holistic strategy provides hope in the field of osteochondral repair.

研究领域: 生物医学工程 · 组织工程 · 骨科 · 再生医学
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Biofabrication · 2022 ·Vol. 14 ·期 2 ·024105 · IF 11.061

A multifunctional micropore-forming bioink with enhanced anti-bacterial and anti-inflammatory properties

Mian Wang,Wanlu Li,Zeyu Luo,Guosheng Tang,Xuan Mu,Xiao Kuang,Jie Guo,Zhibo Zhao,Regina Sanchez Flores,Zewei Jiang,Liming Lian,Julia Olga Japo,Amir M Ghaemmaghami,Yu Shrike Zhang

Three-dimensional (3D) bioprinting has emerged as an enabling tool for various biomedical applications, such as tissue regeneration and tissue model engineering. To this end, the development of bioinks with multiple functions plays a crucial role in the applications of 3D bioprinting technologies. In this study, we propose a new bioink based on two immiscible aqueous phases of gelatin methacryloyl (GelMA) and dextran, further endowed with anti-bacterial and anti-inflammatory properties. This micropore-forming GelMA-dextran (PGelDex) bioink exhibited excellent printability with vat-polymerization, extrusion, and handheld bioprinting methods. The porous structure was confirmed after bioprinting, which promoted the spreading of the encapsulated cells, exhibiting the exceptional cytocompatibility of this bioink formulation. To extend the applications of such a micropore-forming bioink, interleukin-4 (IL-4)-loaded silver-coated gold nanorods (AgGNRs) and human mesenchymal stem cells (MSCs) were simultaneously incorporated, to display synergistic anti-infection behavior and immunomodulatory function. The results revealed the anti-bacterial properties of the AgGNR-loaded PGelDex bioink for both Gram-negative and Gram-positive bacteria. The data also indicated that the presence of IL-4 and MSCs facilitated macrophage M2-phenotype differentiation, suggesting the potential anti-inflammatory feature of the bioink. Overall, this unique anti-bacterial and immunomodulatory micropore-forming bioink offers an effective strategy for the inhibition of bacterial-induced infections as well as the ability of immune-regulation, which is a promising candidate for broadened tissue bioprinting applications.

CAS / MDL: 9048-71-9 9004-54-0
研究领域: 生物医学工程 · 组织工程 · 材料科学 · 免疫学
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Photo-Activatable Substrates for Site-Specific Differentiation of Stem Cells

Kai Han,Wei-Na Yin,Jin-Xuan Fan,Feng-Yi Cao,Xian-Zheng Zhang

In this report, a UV sensitive, PEGylated PFSSTKTC (Pro-Phe-Ser-Ser-Thr-Lys-Thr-Cys) peptide was modified on quartz substrate to investigate the spatial controlled differentiation of stem cells. This substrate could restrict the cell adhesion due to the steric hindrance of PEG shell. With UV irradiation, PFSSTKTC became exposed owing to the breakage of o-nitrobenzyl group with the detachment of PEG shell. The irradiation boundary on substrate was stable in the long term. The in vitro osteogenic differentiation results revealed that under the site-specific irradiation, the mesenchymal stem cells (MSCs) could specifically differentiate into osteoblast under the induction of PFSSTKTC peptide. This photoactivatable biomaterial shows great potential for region controllable and precise MSCs differentiation.

研究领域: 生物材料 · 干细胞生物学 · 组织工程
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Materials Today Communications · 2023 · IF 3.8

Preparation of porous Zn-Li alloy scaffolds for bone repair and its degradation behavior in vitro and in vivo

Shi Qiu,Fengdong Sun,Chen You,Chaokun Tang,Baoli Zhou,Shuquan Zhang,Jiangtao Feng,Aixian Tian,Minfang Chen

Through preparing the porous Zn-0.8Li scaffolds with 50–70 % porosity by using NaCl particles as pore-forming agents in the range of 150–350 µm and 350–550 µm with the infiltration casting method, the present study investigated the pore structure , mechanical properties and weight loss in simulated body fluids (SBF), and conducted the cellular activity and in vivo degradation experiments on porous Zn-0.8Li scaffolds before and after chitosan coating treatment. The results showed that the porous samples with small pore size had higher mechanical properties and lower degradation rate. However, with relatively higher average porosity and through-porosity, the porous samples with large pore size showed better pore connectivity, which provided channels for nutrient transport and promoted the lateral growth of internal tissues. In terms of cell experiments, chitosan coated Zn-0.8Li scaffolds with large pore size had better cell activity and adhesion. Since the coating of chitosan inhibited the release of Zn 2+ during the implantation of porous Zn-0.8Li scaffolds in vivo, it effectively promoted the growth of new bone tissue around the porous scaffolds, which provided an ideal microenvironment for the adhesion, proliferation and differentiation of MSCS. The results of this study demonstrated the great potential of chitosan coated porous biodegradable Zn-based scaffolds for bone tissue engineering.

CAS / MDL: 9012-76-4 7647-14-5
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 生物材料
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Advanced Healthcare Materials · 2023 · IF 10

Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate in Vitro and Enhances Bone Remodeling in Vivo

Xiaomeng Li,Shuaibing Liu,Shanshan Han,Qingqing Sun,Jianmin Yang,Yuhang Zhang,Yongchao Jiang,Xiaofeng Wang,Qian Li,Jianglin Wang

Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through three-dimensional (3D) and spatiotemporal changes in vivo. The matrix stiffness as a crucial factor during bone tissue development is dynamic stiffening. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, we create a dynamic and controllable stiffening 3D biomimetic model to regulate the osteoblastic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. Our findings showed that these dynamic hydrogels allowed cells to spread and volume expansion prior to secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, presented the significantly elevated osteogenic ECM secretion, gene expression, and YAP/TAZ nuclear localization. In vivo evaluation of animal experiments further indicated that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promoted bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo. This article is protected by copyright. All rights reserved

CAS / MDL: 50-81-7 50-02-2
研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学 · 生物力学
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ACS Applied Materials & Interfaces · 2014 · IF 5.9

Cleavable PEGylation and Hydrophobic Histidylation of Polylysine for siRNA Delivery and Tumor Gene Therapy

Haiyan Zhu,Chunyan Dong,Haiqing Dong,Tianbin Ren,Xuejun Wen,Jiansheng Su,Yongyong Li

Polylysine with cleavable PEGylation and hydrophobic histidylation (mPEG-SS-Lysn-r-Hism) was designed and developed for efficient siRNA delivery and tumor therapy. mPEG-SS-Lysn-r-Hism was used to carry and deliver small interfering RNA (siRNA) for silencing endogenous vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth in HepG2 tumor-bearing mice. In this gene vector, histidine(Bzl) was selected for hydrophobic histidylation for the proton sponge ability of the imidazole ring and hydrophobic benzyl group. Cleavable PEGylation was introduced for in vivo circulation as well as selective PEG detachment in response to intracellular reduction condition in order to release the genetic payload. PEG detachment induced gene release was supported by agarose gel electrophoresis retardation assay, undertaken in the intracellular relevant reduction condition. In vitro transfection evaluation of histidylated copolymers, using pEGFP as genetic model, indicated significantly higher GFP expression than unmodified counterparts, comparable to the gold standard PEI. The efficacy of hydrophobic histidylation was found to be pronounced in mesenchymal stem cells (MSCs). In vivo application of the VEGF-siRNA package by tailored mPEG-SS-Lysn-r-Hism showed distinct tumor suppression in terms of macroscopic tumor volume and molecular analysis.

研究领域: 药学 · 分子生物学 · 基因治疗 · 癌症研究
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