Inhibiting mechanotransduction prevents scarring and yields regeneration in a large animal model DOI
Shamik Mascharak, Michelle Griffin, Heather E. Talbott

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(786)

Published: Feb. 19, 2025

Modulating mechanotransduction by inhibiting yes-associated protein (YAP) in mice yields wound regeneration without scarring. However, rodents are loose-skinned and fail to recapitulate key aspects of human repair. We sought elucidate the effects YAP inhibition red Duroc pig wounds, most human-like model show that one-time treatment with verteporfin, a inhibitor, immediately after wounding is sufficient prevent scarring drive pigs. By performing single-cell RNA sequencing (scRNA-seq) on porcine wounds conjunction spatial proteomic analysis, we found perturbations fibroblast dynamics verteporfin presence putative pro-regenerative/profibrotic fibroblasts enriched regenerating/scarring respectively. also identified differences myeloid cell subpopulations linked this observation increased elaboration interleukin-33 (IL-33) regenerating wounds. Finally, validated our findings xenograft containing neonatal foreskin engrafted onto nude used scRNA-seq cells draw parallels subpopulation Collectively, provide support for clinical translation local inhibitors skin scarring, they clarify YAP/IL-33 signaling axis large animal regeneration.

Language: Английский

A Review on the Design of Hydrogels With Different Stiffness and Their Effects on Tissue Repair DOI Creative Commons
T. David Luo, Bowen Tan,

Lengjing Zhu

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Jan. 25, 2022

Tissue repair after trauma and infection has always been a difficult problem in regenerative medicine. Hydrogels have become one of the most important scaffolds for tissue engineering due to their biocompatibility, biodegradability water solubility. Especially, stiffness hydrogels is key factor, which influence morphology mesenchymal stem cells (MSCs) differentiation. The researches on this point are meaningful field engineering. Herein, review focus design with different effects behavior MSCs. In addition, effect hydrogel phenotype macrophages introduced, then relationship between changes inflammatory response discussed. Finally, future application certain medicine prospected.

Language: Английский

Citations

115
Framework Nucleic Acid‐Based Selective Cell Catcher for Endogenous Stem Cell Recruitment DOI Open Access
Xingyu Chen, Ziang Xu, Yang Gao

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

Abstract Cell‐surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature membranes often complicate ligand–receptor interactions. The aim this study is to harness innovative potential programmable tetrahedral framework nucleic acid (tFNA) enable precise, tunable interactions, thereby improving recruitment efficiency. This approach involves experimental screening theoretical analysis using dissipative particle dynamics. results demonstrate that altering flexibility topology ligands on tFNA changes their membrane binding Furthermore, optimizing distribution mesenchymal (MSC)‐binding aptamer 19S (Apt19S) enhances capture Following successful vitro MSC capture, Apt19S‐modified chemically linked a hyaluronic hydrogel, forming an efficient “stem catcher” system. Subsequent vivo experiments system effectively promotes early accelerates bone regeneration different healing scenarios, including cranial maxillary defects.

Language: Английский

Citations

17
Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells DOI Creative Commons
Cheng Zhang, Hongyuan Zhu, Xinru Ren

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 28, 2021

Abstract Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course development, beginning from early stages in which are typically surrounded by other and continuing through later extracellular matrix. How erase memory some these microenvironments while locking others is unknown. Here, we develop a material culture system for modifying measuring degree to retain Using this system, discover that RGD adhesive motif fibronectin (representative matrix), known impart what often termed “mechanical memory” mesenchymal via nuclear YAP localization, erased HAVDI N-cadherin cell-cell contacts). These can be explained motor clutch model relates cellular traction force, deformation, resulting re-localization. Results demonstrate controlled storage removal proteins associated with possible defined programmable systems.

Language: Английский

Citations

67
Anisotropic Hybrid Hydrogels Constructed via the Noncovalent Assembly for Biomimetic Tissue Scaffold DOI
Xinghuan Lin, Xin Xing, Shanshan Li

et al.

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(21)

Published: Feb. 10, 2022

Abstract Anisotropic structure is key for exploring the biomimetic functions of anisotropic hydrogels. However, hydrogel study should not be limited to its architecture design but must include understanding and improvement internal interaction among their components. Herein, a noncovalent mediated assembly strategy proposed simultaneously improve chitin chain mobility enhance interfacial interaction, achieving chitin/2D material (molybdenum disulfide brushite as example) hydrogels via mechanical deformation. Tannic acid (TA) used i) introduce dynamic crosslinking chains affording considerable molecular allow alignment under deformation; ii) chitin–2D benefiting 2D materials orientation driving. The concept achieves multiple crosslinks (chitin–chitin, chitin–TA, chitin–TA–2D) nanofibrous morphology, leading superior performance. chitin–TA/brushite effectively accelerates bone regeneration by promoting cell osteogenic differentiation directional migration, showing potential in tissue engineering. It anticipated that could fabricate other polymer based composite diverse applications.

Language: Английский

Citations

60
How the mechanical microenvironment of stem cell growth affects their differentiation: a review DOI Creative Commons
Xiaofang Zhang, Sibo Zhang, Tianlu Wang

et al.

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 13, 2022

Abstract Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem still a challenge. In addition to chemical factors, physical signals are an important component the ecotone. The mechanical microenvironment cells has huge role differentiation. Herein, we describe knowledge accumulated date on environment which exist, consists various including extracellular matrix topology, substrate stiffness, shear stress, hydrostatic pressure, tension, microgravity. We then detail currently known signalling pathways that use perceive environment, those involving nuclear factor-kB, nicotinic acetylcholine receptor, piezoelectric mechanosensitive ion channel, hypoxia-inducible factor 1α. Using this information clinical settings treat diseases goal research, progress been made. review, examined effects factors growth differentiation, how transmitted function within cell, influence applications.

Language: Английский

Citations

47
Stiff Substrate Induces Nucleus Pulposus Cell Ferroptosis via YAP and N‐Cadherin Mediated Mechanotransduction DOI

Wencan Ke,

Zhiwei Liao, Huaizhen Liang

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(23)

Published: April 6, 2023

Increased tissue stiffness is associated with various pathological processes, such as fibrosis, inflammation, and aging. The matrix of the nucleus pulposus (NP) tissues increases gradually during intervertebral disc degeneration (IDD), while mechanism through which NP cells sense react to remains unclear. In this study, results indicate that ferroptosis involved in stiff substrate-induced cell death. expression acyl-CoA synthetase long-chain family member 4 (ACSL4) group, mediates lipid peroxidation cells. addition, substrate activates hippo signaling cascade induces nuclear translocation yes-associated protein (YAP). Interestingly, inhibition YAP efficient reverse increase ACSL4 caused by stiffness. Furthermore, suppresses N-cadherin overexpression can inhibit via formation N-cadherin/β-catenin/YAP complex, stiffness-induced Finally, effects on IDD progression are further illustrated animal models. These findings reveal a new mechanotransduction cells, providing novel insights into development therapies for treatment IDD.

Language: Английский

Citations

25
Mechanical memory stored through epigenetic remodeling reduces cell therapeutic potential DOI
Adrienne K. Scott, Eduard Casas, Stephanie E. Schneider

et al.

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(8), P. 1428 - 1444

Published: March 4, 2023

Language: Английский

Citations

24
Quantum-enhanced diamond molecular tension microscopy for quantifying cellular forces DOI Creative Commons
Feng Xu, Shuxiang Zhang, Linjie Ma

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(4)

Published: Jan. 24, 2024

The constant interplay and information exchange between cells the microenvironment are essential to their survival ability execute biological functions. To date, a few leading technologies such as traction force microscopy, optical/magnetic tweezers, molecular tension–based fluorescence microscopy broadly used in measuring cellular forces. However, considerable limitations, regarding sensitivity ambiguities data interpretation, hindering our thorough understanding of mechanobiology. Here, we propose an innovative approach, namely, quantum-enhanced diamond tension (QDMTM), precisely quantify integrin-based cell adhesive Specifically, construct force-sensing platform by conjugating magnetic nanotags labeled, force-responsive polymer surface membrane containing nitrogen-vacancy centers. Notably, forces will be converted into detectable variations QDMTM. After careful validation, achieved quantitative mapping correlating measurement with established theoretical model. We anticipate method can routinely studies like cell-cell or cell-material interactions mechanotransduction.

Language: Английский

Citations

9
Cell–matrix feedback controls stretch-induced cellular memory and fibroblast activation DOI Creative Commons
Yuan Hong,

Xiangjun Peng,

Haomin Yu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)

Published: March 18, 2025

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing procedures such as skin grafting, increases with mechanical stimulus for cells cultured two-dimensional but is highly variable three-dimensional (3D) tissue. Here, we show that static of 3D tissues either increase or decrease fibroblast activation depending upon recursive cell–extracellular matrix (ECM) feedback demonstrate control this through integrated vitro mathematical models. ECM viscoelasticity, signaling dynamics, cell mechanics combine yield a predictable, nonmonotonic, relationship between long-term activation. Results determine how retain memory have direct implications improving outcomes grafting procedures.

Language: Английский

Citations

1
Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation DOI Creative Commons
Zheng Zhang,

Baoyong Sha,

Lingzhu Zhao

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 11, 2022

Abstract During mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to cell-extracellular matrix (ECM) interactions. Transduction associated signals is critical for but how these converge regulate human stem (hMSCs) mechanosensing not fully understood, in part because time-evolving cannot readily be presented vitro. Here, we established a DNA-driven cell culture platform that could programmed present RGD peptide fibronectin, mimicking cell-ECM interactions, and HAVDI N-cadherin, through DNA hybridization toehold-mediated strand displacement reactions. The mimic evolving during development. We applied this reveal RGD/integrin ligation promoted cofilin phosphorylation, while HAVDI/N-cadherin inhibited phosphorylation. Cofilin phosphorylation upregulated perinuclear apical actin fibers, which deformed nucleus thereby induced YAP nuclear localization hMSCs, resulting subsequent osteogenic differentiation. Our programmable broadly applicable study dynamic, integrated mechanobiological healing, tissue engineering.

Language: Английский

Citations

32