Engineered microenvironment for the study of myofibroblast mechanobiology

Xu, Ying; Koya, Richard C.; Ask, Kjetil; Zhao, Ruogang

doi:10.1111/wrr.12955

Cited by 8 publications

(7 citation statements)

References 74 publications

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“…Created with BioRender.com cantilevers using atomic force microscopy and traction force microscopy. [135][136][137][138] Fibroblast cell biology was greatly advanced by combining the ECM compositional environment with dimensional cues and mechanical stress. It is long appreciated that tissue fibroblasts do not typically grow on two-dimensional surfaces, let alone on such made of plastic, but interact with malleable ECM in three dimensions (3D).…”

Section: Methods To Study Fibroblast Mechanobiologymentioning

confidence: 99%

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Sawant

Hinz

Schönborn

et al. 2021

Wound Repair Regeneration

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Our skin is continuously exposed to mechanical challenge, including shear, stretch, and compression. The extracellular matrix of the dermis is perfectly suited to resist these challenges and maintain integrity of normal skin even upon large strains. Fibroblasts are the key cells that interpret mechanical and chemical cues in their environment to turnover matrix and maintain homeostasis in the skin of healthy adults. Upon tissue injury, fibroblasts and an exclusive selection of other cells become activated into myofibroblasts with the task to restore skin integrity by forming structurally imperfect but mechanically stable scar tissue. Failure of myofibroblasts to terminate their actions after successful repair or upon chronic inflammation results in dysregulated myofibroblast activities which can lead to hypertrophic scarring and/or skin fibrosis. After providing an overview on the major fibrillar matrix components in normal skin, we will interrogate the various origins of fibroblasts and myofibroblasts in the skin. We then examine the role of the matrix as signaling hub and how fibroblasts respond to mechanical matrix cues to restore order in the confusing environment of a healing wound.

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Section: Methods To Study Fibroblast Mechanobiologymentioning

confidence: 99%

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Sawant

Hinz

Schönborn

et al. 2021

Wound Repair Regeneration

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“…), the fibroblasts become activated, transdifferentiate into myofibroblasts, and express high levels of VIM and α-SMA. The myofibroblasts regulate repair and growth mechanisms within leaflets and cause greater gene expression of collagen (COLA1). , Further, the combined exposure to non-native stresses and bone-related growth factors can cause activated fibroblasts to transdifferentiate into osteoblasts, characterized by the expression of BGLAP . Also, growth factors such as TGF-β1 and TGF-β3 regulate VIC activation, proliferation, differentiation, and migration .…”

Section: Resultsmentioning

confidence: 99%

Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering

Snyder

Jana

2023

ACS Biomater. Sci. Eng.

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Heart valve leaflets have a complex trilayered structure with layer-specific orientations, anisotropic tensile properties, and elastomeric characteristics that are difficult to mimic collectively. Previously, trilayer leaflet substrates intended for heart valve tissue engineering were developed with nonelastomeric biomaterials that cannot deliver native-like mechanical properties. In this study, by electrospinning polycaprolactone (PCL) polymer and poly(l-lactide-co-ε-caprolactone) (PLCL) copolymer, we created elastomeric trilayer PCL/PLCL leaflet substrates with native-like tensile, flexural, and anisotropic properties and compared them with trilayer PCL leaflet substrates (as control) to find their effectiveness in heart valve leaflet tissue engineering. These substrates were seeded with porcine valvular interstitial cells (PVICs) and cultured for 1 month in static conditions to produce cell-cultured constructs. The PCL/PLCL substrates had lower crystallinity and hydrophobicity but higher anisotropy and flexibility than PCL leaflet substrates. These attributes contributed to more significant cell proliferation, infiltration, extracellular matrix production, and superior gene expression in the PCL/PLCL cell-cultured constructs than in the PCL cell-cultured constructs. Further, the PCL/PLCL constructs showed better resistance to calcification than PCL constructs. Trilayer PCL/PLCL leaflet substrates with native-like mechanical and flexural properties could significantly improve heart valve tissue engineering.

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“…MFs are minimally present in healthy tissue, and are implicated in a wide range of CVDs, including MI, hypertrophy, and cardiac fibrosis, and obtaining MFs through CF differentiation is essential to accurately model the damaged myocardium and any related endogenous response [35,159]. Recently, interest has grown in modeling the CF and MF interplay even outside the scope of interactions with CMs [170].…”

Section: Cells In Cardiac Tissue Engineeringmentioning

confidence: 99%

Engineering the cardiac tissue microenvironment

Ronan,

Bahcecioglu,

Aliyev

et al. 2023

Prog. Biomed. Eng.

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In this article we review the microfabrication approaches, with a focus on bioprinting and organ-on-chip technologies, used to engineer cardiac tissue. First, we give a brief introduction to heart anatomy and physiology, and the developmental stages of the heart from fetal stages to adulthood. We also give information on the cardiac tissue microenvironment, including the cells residing in the heart, the biochemical composition and structural organization of the heart extracellular matrix, the signaling factors playing roles in heart development and maturation, and their interactions with one another. We then give a brief summary of both cardiovascular diseases and the current treatment methods used in the clinic to treat these diseases. Second, we explain how tissue engineering recapitulates the development and maturation of the normal or diseased heart microenvironment by spatially and temporally incorporating cultured cells, biomaterials, and growth factors (GF). We briefly expand on the cells, biomaterials, and GFs used to engineer the heart, and the limitations of their use. Next, we review the state-of-the-art tissue engineering approaches, with a special focus on bioprinting and heart-on-chip technologies, intended to (i) treat or replace the injured cardiac tissue, and (ii) create cardiac disease models to study the basic biology of heart diseases, develop drugs against these diseases, and create diagnostic tools to detect heart diseases. Third, we discuss the recent trends in cardiac tissue engineering, including the use of machine learning, CRISPR/Cas editing, exosomes and microRNAs, and immune modeling in engineering the heart. Finally, we conclude our article with a brief discussion on the limitations of cardiac tissue engineering and our suggestions to engineer more reliable and clinically relevant cardiac tissues.

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Engineered microenvironment for the study of myofibroblast mechanobiology

Cited by 8 publications

References 74 publications

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

A story of fibers and stress: Matrix‐embedded signals for fibroblast activation in the skin

Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering

Engineering the cardiac tissue microenvironment

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