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Biomaterials Advances · 2024 · IF 5.5

Impact of surface biofunctionalization strategies on key effector cells response in polyacrylamide hydrogels for bone regeneration

Yi Zhang,Jinjun Dai,Ruiyue Hang,Xiaohong Yao,Long Bai,Di Huang,Ruiqiang Hang

Despite the clinical prevalence of various bone defect repair materials, a full understanding of their influence on bone repair and regeneration remains elusive. This study focuses on poly(acrylamide) (PAAm) hydrogels, popular 2D model substrates, which have regulable mechanical properties within physiological. However, their bio-inert nature requires surface biofunctionalization to enhance cell-material interactions and facilitate the study of bone repair mechanisms. We utilized PAAm hydrogels of varying stiffness (18, 76 and 295 kPa), employed sulfosuccinimidyl-6-(4′-azido-2′-nitropheny-lamino) hexanoate (sulfo-SANPAH) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride/N-hydroxysuccinimidyl acrylate (EDC/NHS) as crosslinkers, and cultured macrophages, endothelial cells, and bone mesenchymal stem cells on these hydrogels. Our findings indicated that sulfo-SANPAH's crosslinking efficiency surpassed that of EDC/NHS, irrespective of pore size and stiffness. Importantly, we observed that the stiffness and surface biofunctionalization method of hydrogels significantly impacted cell adhesion and proliferation. The collagen-modified hydrogels by EDC/NHS strategy failed to support the normal biological behavior of bone mesenchymal stem cells and hindered endothelial cell spreading. In contrast, these modified hydrogels by the sulfo-SANPAH method showed good cytocompatibility with the three types of cells. This study underscores the critical role of appropriate conjugation strategies for PAAm hydrogels, providing valuable insights for hydrogel surface modification in bone repair and regeneration research.

研究领域: 生物材料 · 组织工程 · 细胞生物学 · 生物医学工程
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Cell Reports · 2024 · IF 7.5

Molecular and spatial signatures of human and rat corpus cavernosum physiopathological processes at single-cell resolution

Yinghao Yin,Yuzhuo Chen,Jiarong Xu,Biao Liu,Yifan Zhao,Xiaoli Tan,Ming Xiao,Yihong Zhou,Xiaoping Zheng,Yanghua Xu,Zhitao Han,Hongji Hu,Zitaiyu Li,Ningjing Ou,Wenfei Lian,Yawei Li,Zhongzhen Su,Yingbo Dai,Yuxin Tang,Liangyu Zhao

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level remains unexplored. In this study, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively chart the spatial cellular landscape of the human and rat CC under normal and disease conditions. We observe differences in the proportions of cell subtypes and marker genes between humans and rats. Based on the analysis of the fibroblast (FB) niche, we also find that the enrichment scores of mechanical force signaling vary across different regions and correlate with the spatial distribution of FB subtypes. In vitro , the soft and hard extracellular matrix (ECM) induces the differentiation of FBs into apolipoprotein (APO)+ FBs and cartilage oligomeric matrix protein (COMP)+ FBs, respectively. In summary, our study provides a cross-species and physiopathological transcriptomic atlas of the CC, contributing to a further understanding of the molecular anatomy and regulation of penile erection.

研究领域: 分子生物学 · 医学 · 生理学
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Journal of Materials Chemistry B · 2024 · IF 6.1

Revelation of Adhesive Proteins Affecting Cellular Contractility through A Reference-free Traction Force Microscopy

Yingjun Yang,Kuankuan Han,Siyuan Huang,Kai Wang,Yuchen Wang,Shukai Ding,Le Zhang,Miao Zhang,Bingshe Xu,Shufang Ma,Yongtao Wang,Shengli Wu,Xinlong Wang

Over the past decades, the critical role of cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-l-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterials design. In this study, a reference-free traction force microscopy with a well-organized microdots array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although the poly-l-lysine supported cell spreading and elongation, it was inefficient in inducting cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.

研究领域: 细胞生物学 · 生物物理学 · 生物材料科学 · 机械生物学
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EUROPEAN JOURNAL OF MEDICAL RESEARCH · 2025 ·Vol. 30 ·期 1 ·1-11 · IF 3.4

Matrix stiffness enhances viability, migration, invasion and invadopodia formation of oral cancer cells via PI3K/AKT pathway in vitro

Zhang Zihao,Ren Jiayi,Tang Ke,Hu Xinyi,Liu Jinhui,Li Chunming

Background Oral cancer (OC) is one of the major types of cancer and the most common cause of cancer-related mortality in Asia. In recent years, matrix stiffness in the tumor microenvironment has been found to play an important role in regulating tumor cell behavior. However, the regulatory mechanisms associated with matrix stiffness in OC cells remain unclear. Methods In this study, polyacrylamide gels with different stiffness were prepared to simulate low versus high matrix stiffness environments in tumor tissues by adjusting the acrylamide and cross-linker concentrations. Subsequently, the effects of different stiffness on OC cell survival, migration, invasion and invadopodia formation were explored based on cell counting kit-8 (CCK-8), Transwell and confocal microscopy. Meanwhile, the levels of markers relevant to phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), apoptosis (BAX and BCL2) as well as metastasis (Cadherin-1, CDH1; Cadherin-2, and CDH2) were calculated via western blotting and real-time quantitative PCR. Results According to the results, high matrix stiffness was seen to contribute to the increased number of migrated and invaded cells as well as the enhanced viability of OC cells, along with the aggravated invadopodia formation and the up-regulation in CDH2 and BCL2 levels yet the down-regulation in CDH1 and BAX levels. Elevated PI3K/AKT phosphorylation levels were also seen in high matrix stiffness-mediated OC cells, and the intervention using LY294002 could visibly overturned the effects of high matrix stiffness on the cell migration, invasion and invadopodia formation of OC cells. Conclusions This study reveals that matrix stiffness may enhance the invasiveness and anti-apoptotic ability of OC cells by activating the PI3K/AKT pathway, which provides a new idea for exploring the microenvironmental regulation of tumor mechanics and targeted intervention strategies.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Colloid and Interface Science Communications · 2025 · IF 4.7

A sugar-responsive dynamic biointerface for the regulation of cell adhesion and macrophage polarization behavior

Pengjia Yan,Wenbo He,Xin Du,Wenxiu Hou,Miao Luo,Changwei Tan,Jinling Luo,Xiaoqian Jiang,Ji Qiu,Ling Bai,Guoqing Pan

Here we report a new strategy for the functionalization of soft polyacrylamide (PAM) hydrogels with a sugar-responsive dynamic biointerface, offering a more accurate mimicry of the cellular microenvironment for cell dynamic adhesion and macrophage polarization. This dynamic platform shows the potential for recapitulating the physiological stiffness of various human tissues, enabling the modulation of cell behaviors through a natural biofeedback mechanism.

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