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ACS Biomaterials Science & Engineering · 2024 · IF 5.4

Poison Turned Panacea: Arsenic Trioxide Loaded Hydrogel for Inhibiting Scar Formation in Wound Healing

Xinyue Xu,Youwei Wang,Changhao Han,Jingsong Lin,Qingan Shen,Youyi Lan,Linjing Long,Xudong Tan,Jiankai Liu,Siyi Liu,Lanxinhui Luo,Mingqi Lv,Yuchan Zhang,Guixue Wang,Guangchao Zang

Without intervention, the natural wound healing process can often result in scarring, which can have detrimental effects on both the physical and mental well-being of patients. Therefore, it is crucial to develop biomaterials that can promote healing without scarring. Regulating the Yes-associated protein-1/PDZ-binding motif (YAP/TAZ) signaling pathway is possible to reduce excessive fibrosis of fibroblasts and proliferation of vascular endothelial cells, ultimately impacting scar formation. Arsenic trioxide (ATO), an ancient drug with medicinal and toxic properties, has shown promise in regulating this pathway. An ATO-loaded hydrogel dressing (ATO@CS/SA) was created to facilitate scarless wound healing, utilizing chitosan (CS) and sodium alginate (SA) to prevent direct contact of ATO with the wound tissue and minimize potential side effects. In vitro studies demonstrated that low concentrations of ATO did not impact cell viability and even promoted proliferation and migration. Co-culturing the hydrogel with fibroblasts and vascular endothelial cells led to decreased expression levels of YAP and TAZ. Animal studies over a 90-day period revealed significant inhibition of scar formation with this system. Histological experiments further confirmed that the decreased expression of YAP and TAZ was responsible for this outcome. In conclusion, when administered at the appropriate dose, ATO can be repurposed from a traditional poison to a therapeutic agent, effectively suppressing excessive cell fibrosis and blood vessel proliferation and offering a novel approach to scar-free treatment.

CAS / MDL: 9012-76-4 9005-38-3
研究领域: 生物医学工程 · 药学 · 组织工程 · 再生医学 · 细胞生物学
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Materials Today Communications · 2023 · IF 3.8

Triazole and methylthio modified covalent organic frameworks for enhancing Hg(II) adsorption from water

Ye Jia,Donghai Zhu,Qifan Yang,Xu Liu,Zahra Gholami,Mohammadtaghi Vakili,Shuangxi Zhou,Wei Wang

The presence of mercury (Hg(II)), a highly toxic pollutant in the aquatic environment, motivates researchers to use an effective method to remove it from water. Herein, we synthesized COF-TAZ and COF-TOE via post-modification with 3-mercapto-1,2,4-triazole and 4-(methylsulfanyl)thiophenol to form triazole group and methylthio group, respectively, and followed by characterization with SEM, FTIR, and XRD, etc. The adsorption behaviors of Hg(II) on two modified COFs were evaluated by adsorption kinetic models using the pseudo-first order, pseudo-second order and intra-particle diffusion models, as well as isotherm models, i.e., Langmuir and Freundlich models. COF-TAZ and COF-TOE manifested maximum experimental uptake capacity of 108.09 mg g −1 and 104.85 mg g −1 , respectively. Notably, COF-TAZ exhibited commendable binding selectivity towards Hg(II) and displayed a good recycling ability, with a removal percentage still above 90% after five cycles. Especially, the adsorption mechanisms of COF-TAZ and COF-TOE were clarified by FTIR, XPS and DFT calculations, suggesting that electrostatic interaction and chelation were involved in the adsorption process . This study shows that functionalized COFs have good application prospects in effective removal of heavy metals in water.

研究领域: 环境科学 · 材料科学 · 化学工程
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 40 ·9314-9324 · IF 5.344

Osteogenesis regulation of mesenchymal stem cells via autophagy induced by silica–titanium composite surfaces with different mechanical moduli

Maowen Chen,Yan Hu,Yanhua Hou,Menghuan Li,Maohua Chen,Lu Tan,Caiyun Mu,Bailong Tao,Zhong Luo,Kaiyong Cai

The high surface elastic modulus of the titanium (Ti) implant is one of the critical factors causing poor osteointegration between the implant surface and surrounding bone tissue. To address this challenge, spherical silica nanoparticles (SSNs) and spherical titania nanoparticles (STNs) with different sizes were synthesized and embedded into Ti surfaces via a micro-arc oxidation (MAO) technique. There were no significant changes in the surface roughness and protein adsorption behaviors before and after the embedding of spherical silica nanoparticles and titania nanoparticles into the Ti implant. However, the surface elastic modulus of Ti-SSNs decreased from 93 GPa to 6.7 GPa, while there was still no change in surface elastic modulus between Ti and Ti-STN groups. In vitro experiments showed that Ti-SSNs, especially Ti-SSN3, significantly stimulated the expression level and nuclear localization of the transcription factor YAP. YAP/TAZ could further inhibit the phosphorylation of AKT and mTOR proteins in MSCs, leading to higher LC3-II protein expression and osteogenic differentiation of MSCs. Ti-SSNs also showed a higher level of autophagosome formation, ALP activity and mineralization capability compared to the other groups. Our results showed that the surface elasticity modulus of an implant plays an important role in the regulation of MSC behaviors. Therefore, designing an implant with an optimal elastic modulus at the surface might have great clinical potential in the bone repair field.

CAS / MDL: 5593-70-4 78-10-4
研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 生物力学 · 骨科研究
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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 Nano · 2025 · IF 16

MicroSphere 3D Structures Delay Tissue Senescence through Mechanotransduction

Ziang Li,Jincheng Tang,Liang Zhou,Jiannan Mao,Wei Wang,Ziyan Huang,Lichen Zhang,Jie Wu,Xinzhao Jiang,Zhouye Ding,Kun Xi,Feng Cai,Yong Gu,Liang Chen

The extracellular matrix (ECM) stores signaling molecules and facilitates mechanical and biochemical signaling in cells. However, the influence of biomimetic “rejuvenation” ECM structures on aging- and degeneration-related cellular activities and tissue repair is not well understood. We combined physical extrusion and precise “on–off” alternating cross-linking methods to create anisotropic biomaterial microgels (MicroRod and MicroSphere) and explored how they regulate the cell activities of the nucleus pulposus (NP) and their potential antidegenerative effects on intervertebral discs. NP cells exhibited aligned growth along the surface of the MicroRod, enhanced proliferation, and reduced apoptosis. This suggests an adaptive cellular response involving adhesion and mechanosensing, which causes cytoskeletal extension via environmental cues. NP cells maintain nuclear membrane integrity through the YAP/TAZ pathway, which activates the cGAS-STING pathway to rectify the aging mechanisms. In vivo, MicroRod carries NP cells and reduces inflammatory factor and protease secretion in degenerated intervertebral discs, inhibiting degeneration and promoting NP tissue regeneration. Our findings highlight the role of mechanical stress in maintaining cellular activity and antiaging effects in harsh environments, providing a foundation for further research and development of antidegenerative biomaterials.

研究领域: 生物材料 · 组织工程 · 力学生物学 · 细胞衰老 · 退行性疾病
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Signal Transduction and Targeted Therapy · 2023 ·Vol. 8 ·期 1 ·1-17 · IF 39.3

Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice

Liu Yi,Ji Yanhong,Jiang Ruiyi,Fang Chao,Shi Gang,Cheng Lin,Zuo Yinan,Ye Yixin,Su Xiaolan,Li Junshu,Wang Huiling,Wang Yuan,Lin Yi,Dai Lei,Zhang Shuang,Deng Hongxin

Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given the increased incidence of cancer and the population ageing trend globally, it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer. In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer (CAC), we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation, although ageing does not affect the incidence of AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through conditional lineage tracing, an important source of fibroblasts potentially derived from intestinal smooth muscle cells (ISMCs) was identified orchestrating intestinal wound healing and CAC initiation in young mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment, decreased intestinal wound healing and decreased CAC initiation, similar to the phenotype of ageing mice. In addition, the data from intestine samples derived from inflammatory bowel disease (IBD) patients show that activation of YAP/TAZ also occurs in ISMCs from these patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.

CAS / MDL: 8001-30-7
研究领域: 胃肠病学 · 肿瘤学 · 老年医学 · 细胞生物学 · 分子生物学
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