Table of Contents
Overview
Definition and Composition
The extracellular matrix (ECM), also referred to as the intercellular matrix (ICM), is a dynamic three-dimensional structure that anchors and surrounds cellular compartments within tissues and organs.[4.1] It is composed of a network of interconnected macromolecular assemblies, including extracellular macromolecules and minerals such as collagen, enzymes, glycoproteins, and hydroxyapatite, which provide essential structural and biochemical support to surrounding cells.[1.1] The composition of the ECM varies among different multicellular structures due to the independent evolution of multicellularity in various lineages; however, common functions of the ECM include facilitating cell adhesion, cell-to-cell communication, and differentiation.[1.1] The ECM primarily consists of water, fibrous proteins, and proteoglycans, with key fibrous proteins including collagens, elastins, and laminins.[3.1] These fibrous proteins contribute to the tensile strength and rigidity of tissues, while proteoglycans help resist compressive forces, maintaining the physical separation and distinctiveness of cells within a tissue.[3.1] The extracellular matrix (ECM) is a dynamic network that provides essential mechanical and biochemical cues, regulating cellular behavior, tissue development, and remodeling.[5.1] Its composition is tissue-specific, with significant variations observed between different types of tissues, as well as changes occurring with age and disease.[11.1] Despite these variations, the ECM consistently facilitates cellular adhesion, communication, and differentiation.[2.1] The ECM acts as an adhesive, holding cells in place while also maintaining physical separation between them, which is crucial for ensuring distinct cellular environments.[3.1] The primary constituents of the ECM include water, fibrous proteins such as collagens, elastins, and laminins, as well as proteoglycans.[3.1] The construction of the ECM is highly regulated during embryonic development and organ homeostasis; however, this regulation can be impaired in conditions such as aging and disease, leading to significant changes in its structural and functional properties.[11.1] Understanding these alterations is vital for developing effective therapeutic strategies for tissue repair and regeneration.[11.1] The extracellular matrix (ECM) is a dynamic network composed of diverse proteins, sugars, and other components that provides both mechanical and biochemical cues essential for regulating cellular behavior.[6.1] It has been established that ECM stiffness significantly influences fundamental cellular processes, including migration, proliferation, differentiation, and organoid formation.[13.1] This mechanical property is particularly critical for fibroblasts, which are the primary producers of the ECM, especially in contexts of inflammation and fibrosis.[12.1] Furthermore, the ECM is not merely a static structure; it undergoes continuous remodeling as cells secrete new matrix proteins and modify existing ones, resulting in spatial and temporal heterogeneity within the tissue microenvironment.[7.1] This complexity highlights the ECM's role beyond structural support, as it actively influences cell structure, organization, and gene expression.[8.1]Functions and Importance
The extracellular matrix (ECM) is a dynamic and complex environment essential for cellular interactions and tissue dynamics. It not only provides structural support but also regulates tissue organization and influences cell behavior through a dynamic dialogue with cellular constituents [16.1]. The ECM's biophysical, mechanical, and biochemical properties vary across tissue types, playing a crucial role in processes such as migration, proliferation, and differentiation [17.1]. Stem cells, vital for tissue maintenance and regeneration, reside within ECM-defined niches, underscoring the ECM's role in cellular interactions [17.2]. Molecular components like collagens, elastin, fibronectin, and proteoglycans modulate cell behavior by providing biochemical signals that affect cell-ECM interactions [18.1]. The concentration and density of these components significantly influence cellular responses [18.2]. Integrins, transmembrane proteins, facilitate communication between cells and the ECM by linking it to the cytoskeleton and activating intracellular signaling pathways [28.1]. This integrin-mediated communication is crucial for tissue repair, directing the behavior of cells involved in rebuilding damaged tissue [27.1]. The ECM's mechanical properties, such as stiffness, are vital in regulating cell fate and behavior through mechanotransduction mechanisms [20.1]. In cancer, changes in ECM composition can promote tumor growth and progression [22.1]. The interplay between ECM stiffness and the tumor microenvironment is critical in cancer initiation and the efficacy of immunotherapeutic strategies [22.2]. Post-translational modifications (PTMs) within the ECM are key events influencing cell behavior during tissue homeostasis and disease progression [36.1]. Identifying these modifications in tissue-specific proteins can reveal unique disease-specific biochemical markers [35.1]. The ECM's diverse composition, including various protein species and sugar polymers, forms distinct microenvironments essential for determining tissue structure and health, affecting cell-matrix interactions and cellular function [37.1]. The concept of "dynamic reciprocity" illustrates the evolving relationship between the ECM and cells, highlighting its importance in developmental biology [38.1]. This reciprocal interaction is fundamental for maintaining tissue homeostasis and facilitating proper development.In this section:
History
Early Theories and Discoveries
The concept of the extracellular matrix (ECM) has evolved significantly over time, beginning with its recognition in the mid-19th century. Around 1850, the discovery of cells in connective tissue led to the acceptance of the cellular theory as the foundation of life. During this period, the material outside cells, which was presumed to be produced by them, was identified as the extracellular matrix.[48.1] The cellular theory emerged as the foundation of life around 1850, following the discovery of cells in connective tissue. This theory led to the recognition of material outside cells, which was presumed to be produced by them, as the extracellular matrix (ECM).[48.1] From 1930 to 1975, advancements in physical and chemical characterization techniques facilitated the identification of various components of the ECM, including essential proteins such as elastin, fibronectin, and laminin, among others.[48.1] Since 1975, the application of molecular and cell biological techniques has demonstrated that the ECM is not merely a passive environment for cells; rather, it is a highly interactive entity that plays a significant role in health and disease.[49.1] The ECM is recognized as a key characteristic of all metazoan organisms, with vertebrates exhibiting a diverse array of matrices that contribute to the formation of specialized tissues such as bone, tendon, and cartilage.[47.1] Despite the long-standing paradigm that "no cells, no ECM" persists, it is noteworthy that the ECM was acknowledged long before the discovery of cells, highlighting its fundamental importance in biological organization.[50.1]Development of ECM Research
The understanding of the extracellular matrix (ECM) has evolved significantly over the years, transitioning from a perception of it as a passive structural component to recognizing its active role in cellular behavior and tissue dynamics. Initially, the ECM was viewed primarily as a mere scaffold providing structural support to cells within tissues. However, contemporary research has established that the ECM is a complex assembly of macromolecules, including proteoglycans and fibrous proteins, which not only supports cells but also delivers crucial biochemical and mechanical signals that influence cell behavior, including adhesion, migration, proliferation, and differentiation.[53.1] This shift in perception has led to the concept of "dynamic reciprocity," which posits that the ECM actively directs cell fate and influences tissue development and homeostasis. This concept underscores the importance of the ECM in embryogenesis and stem cell differentiation, as it interacts with cellular receptors to initiate intracellular signaling and gene transcription.[56.1] Furthermore, the ECM's mechanical properties have been shown to significantly affect cellular activity and fate, highlighting its role in mechanotransduction—the process by which cells convert mechanical stimuli into biochemical signals.[55.1] Recent advancements in molecular techniques, particularly CRISPR activation, have enabled the rapid and stable upregulation of cell surface proteins, which is essential for studying extracellular interactions necessary for signaling and adhesion. However, identifying these interactions remains technically challenging.[60.1] The extracellular matrix (ECM) serves not only as a structural scaffold but also as an active regulator of cancer progression, profoundly influencing tumor behavior and the tumor microenvironment.[62.1] Research increasingly emphasizes the significance of the cancer-associated ECM, as biochemical and physical signals from the ECM affect tumor formation, invasion, metastasis, and therapy resistance.[64.1] Understanding these interactions is crucial for developing therapeutic strategies aimed at counteracting ECM alterations that facilitate tumor metastasis.[62.1] As research continues to uncover the complexities of the ECM, its implications for personalized medicine are becoming increasingly apparent. Tailoring therapies based on individual ECM profiles may lead to more effective treatment strategies, particularly in oncology, where the ECM's biochemical and physical signals can impact tumor formation, invasion, and therapy resistance.[64.1] Thus, the development of ECM research reflects a broader understanding of its integral role in both normal physiology and disease, paving the way for innovative therapeutic approaches.Recent Advancements
Innovations in Tissue Engineering
Recent advancements in the understanding of the extracellular matrix (ECM) have significantly influenced the design and functionality of biomaterials used in tissue engineering. The ECM serves as nature's template for ideal biomaterials, guiding tissue homeostasis and repair, which has led to the development of matrix-mimicking biomaterials and decellularized matrices that replicate the natural ECM environment.[106.1] These innovations are crucial for creating functional complex biomaterials that leverage ECM proteins in their natural form, enhancing their effectiveness in clinical applications.[105.1] One of the key areas of focus has been the incorporation of biochemical and biophysical cues derived from the ECM into engineered biomaterials. This approach aims to modulate stem cell fate by replicating the properties of the ECM, thereby promoting efficient differentiation and maturation of stem cells.[107.1] For instance, recent research highlights the importance of ECM stiffness as a mechanical cue that influences stem cell behavior, impacting their differentiation during tissue development and regeneration.[102.1] Moreover, advancements in characterizing cell-matrix interactions have provided insights into the complex intermolecular interactions that occur within the ECM, which are vital for cell migration and organ formation.[96.1] This understanding has led to the identification of distinctive modes of cell migration in various 3D ECMs, further enhancing the design of biomaterials that can effectively support tissue engineering applications.[96.1]Analytical Technologies for ECM Study
Recent advancements in analytical technologies have significantly enhanced the study of the extracellular matrix (ECM), particularly in the context of cancer and fibrosis. A comprehensive understanding of the ECM's role in these diseases necessitates the integration of various analytical approaches that can capture its complex composition and mechanical properties. Recent advancements in the study of the extracellular matrix (ECM) have led to the development of a comprehensive tissue atlas that integrates both static and dynamic mechanical measurements with data on ECM composition and organization, as well as cell identity and differentiated states.[114.1] This atlas is particularly significant in the context of progressive lung fibrosis, where pathological changes in the ECM can impair organ function.[114.1] By accounting for multiple parameters, such as ECM stiffness, dimensionality, viscoelasticity, cyclic stretch, and cell-cell interactions, researchers can construct models that reflect the in vivo biology of fibrosis.[116.1] The ECM in the fibrogenic niche is compartmentalized, with its mechanical properties and composition organized to support and guide the various cells involved in fibrosis progression, including self-renewing mesenchymal progenitor cells, actively proliferating transit-amplifying cells, and pathological myofibroblasts.[116.1] With a robust dataset derived from this atlas, investigators are positioned to generate testable models that identify targetable pathways critical to fibrosis progression, based on the precise mechanical properties sensed by cells, the ECM components they interact with, and the resulting cellular responses.[116.1] Moreover, the interplay between ECM stiffness and the tumor microenvironment has been recognized as a critical factor in cancer progression. Analytical techniques that assess ECM stiffness can reveal how mechanical properties regulate malignant behaviors in cancer cells, thereby informing therapeutic strategies aimed at enhancing the efficacy of immunotherapies.[113.1] For instance, studies have shown that increased ECM stiffness can promote tumor cell proliferation and invasion, highlighting the importance of mechanical properties in the tumor microenvironment.[115.1] The extracellular matrix (ECM) undergoes significant alterations during tumor progression at both primary and secondary sites, encompassing various biochemical and biophysical changes.[133.1] Cancer cells and tumor-associated stromal cells actively modify all four ECM remodeling mechanisms, resulting in a cancer-supporting matrix that contributes to tumor pathology.[134.1] Tumor-derived factors play a crucial role in activating stromal cells, which differentiate into cancer-associated fibroblasts (CAFs). These CAFs secrete and deposit large amounts of ECM components alongside cancer cells, thereby facilitating tumor growth.[134.1] Additionally, stromal cells in the pre-metastatic niche are activated by these tumor-derived factors, leading to ECM remodeling characterized by the deposition of specific components such as fibronectin, tenascin C, osteopontin, and versican, depending on the tissue context.[134.1] Understanding these alterations in ECM composition and structure is essential for elucidating the mechanisms by which the tumor microenvironment supports cancer progression and metastasis.[133.1]Structural Components
Major ECM Proteins
The extracellular matrix (ECM) is primarily composed of a variety of proteins that play crucial roles in maintaining tissue structure and function. Among these, fibrous proteins such as collagens, elastins, and laminins are fundamental components. Collagens are the most abundant proteins in the ECM, providing tensile strength and structural integrity to tissues. Elastins contribute to the elasticity of the ECM, allowing tissues to withstand stretching and deformation. Laminins are key glycoproteins that facilitate cell adhesion and influence cell behavior within the ECM.[143.1] The extracellular matrix (ECM) is a dynamic, three-dimensional (3D) network composed of over 300 macromolecules, including proteins, glycoproteins, and polysaccharides, which surround and support cells in various tissues and organs.[144.1] Among its key components are fibrous proteins, such as collagens, elastins, and laminins, which provide tensile strength and rigidity to tissues by resisting stretching.[143.1] In contrast, proteoglycans play a crucial role in resisting compressive forces, contributing to the hydration and resilience of the matrix.[143.1] Additionally, adhesive proteins, including fibronectin and integrins, facilitate cell-matrix interactions and are involved in the formation of supramolecular assemblies like collagen fibrils and elastic fibers.[141.1] The ECM not only maintains the structural integrity of tissues but also provides biochemical signals essential for processes such as angiogenesis, tissue development, and wound healing, thereby influencing cell growth and behavior.[144.1] The extracellular matrix (ECM) is a dynamic microenvironment that plays a crucial role in regulating stem cell behavior during tissue development and regeneration. It is primarily composed of various components, particularly adhesive proteins such as fibronectin, which interact with cell surface receptors, including integrins and non-integrin receptors. These interactions are essential for the formation of supramolecular assemblies, such as collagen fibrils and elastic fibers, which contribute to tissue architecture and influence cell-matrix interactions that regulate cell growth and behavior.[141.1] Within the stem cell niche, the ECM provides critical chemical cues through its components, including growth factors and associated signaling molecules. The ECM/integrin interaction within the stem cell niche is fundamental for three main functions: (1) cell-matrix anchorage, where integrin-mediated adhesion physically anchors stem cells to ECM proteins, (2) the regulation of stem cell differentiation, and (3) the provision of mechanical and biochemical signals that guide stem cell behavior.[141.1] This interplay between the ECM and stem cells is vital for maintaining proper tissue homeostasis and facilitating regeneration.Glycoproteins and Proteoglycans
Fibronectin (FN) is a significant glycoprotein within the extracellular matrix (ECM) that plays a crucial role in various physiological processes, particularly in cell behavior. It is involved in cell adhesion, spreading, migration, proliferation, and differentiation, highlighting its pivotal role in controlling cellular dynamics.[150.1] FN facilitates these processes by forming essential connections between cell surface integrin receptors and structural components of the ECM, thereby influencing tissue formation and cell differentiation.[149.1] The mechanoregulatory functions of fibronectin are particularly important in contexts such as wound repair, cancer metastasis, and vertebrate development, where FN-mediated cell migration is essential.[146.1] Fibronectin is assembled by cells into viscoelastic fibrils that can bind to numerous growth factors and cytokines, thus regulating cell signaling pathways and contributing to the overall structural integrity of the ECM.[147.1] Moreover, fibronectin's multidomain structure allows it to bind simultaneously to various cell surface receptors, collagen, proteoglycans, and other fibronectin molecules, facilitating complex interactions that are vital for cellular communication and ECM assembly.[151.1] Recent studies have identified specific binding sites within fibronectin for integrin families and proteoglycans, further elucidating its role as an adhesive protein that promotes cell adhesion.[148.1] Overall, fibronectin serves as a critical component of the ECM, influencing not only the physical structure of tissues but also the biochemical signals that govern cell behavior.In this section:
Ecm In Development And Disease
Role in Tissue Development
The extracellular matrix (ECM) plays a pivotal role in tissue development, serving as a crucial non-cellular component that provides both physical support and regulatory signals to cells. It is synthesized and secreted by embryonic cells from the earliest stages of development, influencing key aspects of cell behavior such as shape, adhesion, migration, and differentiation.[199.1] The ECM is highly dynamic, undergoing constant deposition, remodeling, and degradation throughout development to maintain tissue homeostasis and facilitate morphogenesis.[200.1] During embryonic development, the composition and organization of the ECM are spatiotemporally regulated, which is essential for proper tissue formation and organogenesis. This regulation affects how cells interact with their environment, thereby directing cell and tissue shape.[200.1] For instance, the ECM influences angiogenesis, the formation of blood vessels, by providing a microenvironment that supports vascular network formation and maturation.[195.1] Additionally, the ECM's diverse protein composition confers distinct biochemical and biophysical properties that significantly impact cell phenotype and behavior.[193.1] The extracellular matrix (ECM) plays a crucial role in both normal development and the pathophysiology of various diseases. It is essential for the integrity of connective tissues, and defects in ECM components can lead to a range of disorders, including muscular dystrophy, fibrosis, and cancer, which are all driven by ECM dysfunction.[192.1] Understanding the ECM's contributions to these conditions is vital for developing improved diagnostics and therapeutic strategies aimed at tissue repair and regeneration.[191.1] Furthermore, advancements in biomaterials inspired by the ECM have emerged as promising approaches in biomedical research and engineering. These ECM-inspired biomaterials possess unique properties that facilitate tissue regeneration, drug delivery, and cellular investigations, thereby addressing the challenges of replicating the dynamic properties of the ECM.[212.1] As research continues to evolve, the insights gained from studying the ECM will likely enhance our ability to create effective interventions for various connective tissue disorders.Implications in Disease Pathology
The extracellular matrix (ECM) is crucial in disease pathology, particularly in cancer, where its composition and organization are spatiotemporally regulated to influence cell behavior and differentiation. Dysregulation of ECM dynamics can lead to the development of various diseases, including cancer, as alterations in tumor cell–ECM interactions drive malignant transformation, invasion, and metastasis, as well as treatment resistance.[202.1] Cancer cells and tumor-associated stromal cells actively modify ECM remodeling mechanisms, creating a cancer-supporting matrix that contributes to tumor pathology.[203.1] Tumor-derived factors activate stromal cells, leading to their differentiation into cancer-associated fibroblasts (CAFs), which secrete and deposit large amounts of ECM components alongside cancer cells.[203.1] Additionally, tumor-associated hypoxia induces the expression of ECM-modifying enzymes, resulting in changes such as fibrillar collagen crosslinking, which enhances the ability of cancer cells to invade and metastasize.[202.1] In cancer, the tumor microenvironment is shaped by both cancer cells and tumor-associated stromal cells, which modify ECM remodeling mechanisms to create a supportive matrix that contributes to tumor pathology.[203.1] For instance, tumor-derived factors activate stromal cells, leading to the differentiation of cancer-associated fibroblasts (CAFs) that secrete and deposit large amounts of ECM components, thereby facilitating tumor growth.[203.1] Additionally, tumor-associated hypoxia induces the expression of ECM-modifying enzymes, resulting in changes such as fibrillar collagen crosslinking, which enhances the invasive capabilities of cancer cells.[202.1] The ECM's influence extends beyond structural support; it also modulates immune responses. For example, lung cancer cells can express higher levels of PD-L1 in response to ECM stiffness, which helps to suppress anti-tumor immune responses mediated by CD8+ T cells.[204.1] This interaction highlights the ECM's role in creating an immunosuppressive environment that promotes tumor progression. The extracellular matrix (ECM) is pivotal in cancer progression, influencing critical processes such as tumor growth, metastasis, and therapy resistance. Variations in ECM composition, including differences in sugar composition, have been observed across different tumor types, which can significantly affect tumor behavior and therapeutic responses.[206.1] Key proteins, particularly tenascin C and fibronectin, play essential roles in the formation of the tumor microenvironment and activate specific signaling pathways in cancer cells.[205.1] Future studies focusing on the mechanistic validation of matrix-related biomarkers are imperative, particularly in large patient cohorts with diverse solid cancers. Such research will enhance our understanding of ECM interactions with other cell types in the tumor microenvironment, including immune cells and fibroblasts, thereby providing greater insights into ECM modeling during cancer progression.[207.1] Mutations in the genes encoding extracellular matrix (ECM) components lead to a variety of genetic connective tissue disorders, highlighting the essential role of ECM integrity in normal development and tissue function.[210.1] These mutations can result in serious inherited disorders, underscoring the importance of understanding the correlation between these genetic alterations and their pathological implications.[210.1] The elucidation of these mutations has been crucial for comprehending the roles of various ECM components and their impact on the functionality of connective tissues.[208.1] As research progresses, insights gained from studying these genetic mutations will be vital for developing potential therapeutic interventions aimed at addressing the dysfunctions associated with these disorders.[208.1]In this section:
Mechanotransduction
Cellular Responses to ECM Mechanics
The mechanical properties of the extracellular matrix (ECM), including stiffness and elasticity, play a crucial role in regulating various cellular behaviors such as differentiation, migration, and proliferation through mechanotransduction. Cells interact with the ECM via integrins, which are heterodimeric transmembrane receptors that connect extracellular signals to intracellular responses. These interactions are mediated by a network of linker proteins that connect integrins to the cytoskeleton, facilitating the transmission of mechanical loads and biochemical signals within the cell.[235.1] Research has shown that the stiffness of the ECM significantly influences stem cell behavior. For instance, stem cells tend to proliferate and migrate towards areas of increased stiffness, which is critical during tissue regeneration processes.[239.1] This phenomenon, known as durotaxis, highlights how cells can sense and respond to the mechanical properties of their environment, thereby influencing their fate and function.[248.1] Additionally, the ECM's mechanical properties are not static; they can change in response to various physiological and pathological conditions, such as during development or in diseases like cancer and fibrosis.[242.1] The dynamic nature of soft connective tissues allows resident cells to continuously read environmental cues and respond accordingly, promoting homeostasis and maintaining the mechanical properties of the ECM essential for cellular and tissue health.[237.1] For example, during embryogenesis, the ECM directs developing tissues by influencing cell adhesion, migration, morphology, and differentiation.[243.1] Specific ECM components, such as collagens and glycoproteins, provide the necessary cues for these processes, demonstrating the intricate relationship between ECM mechanics and cellular responses.[245.1] Moreover, the understanding of how ECM mechanics influence cellular behavior has significant implications for tissue engineering. By manipulating the mechanical properties of biomaterials, researchers can design scaffolds that better mimic the natural ECM, thereby enhancing cell adhesion, migration, and differentiation in engineered tissues.[250.1] This approach underscores the importance of mechanotransduction in developing effective strategies for regenerative medicine and tissue repair.ECM Influence on Signaling Pathways
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are critical components of the extracellular matrix (ECM) that play significant roles in cellular mechanosensing pathways. These molecules, including heparan sulfate (HS) and chondroitin sulfate (CS), interact with various cell surface receptors, such as integrins, to facilitate mechanotransduction processes.[247.1] The interaction between GAGs, PGs, and cell surface receptors is essential for translating mechanical signals from the ECM into biochemical responses within the cell, thereby influencing cellular functions such as migration and differentiation.[266.1] The mechanotransduction process involves a complex network of molecules that mechanically couple the ECM to the cytoskeleton and nucleoskeleton, allowing cells to respond to mechanical stimuli.[268.1] During integrin-mediated cell-ECM adhesion, this network is crucial for the transduction of mechanical signals into biochemical cascades, which can lead to various cellular responses.[267.1] For instance, strain on the actin cytoskeleton can activate signaling pathways, such as c-Src activation, which is mediated by actin filament-associated proteins like AFAP-110.[269.1] Moreover, the ECM's biochemical and biophysical cues significantly modulate stem cell fate, as the extracellular environment varies in composition over time and space.[272.1] Engineering synthetic biomaterials that mimic the properties of the ECM can incorporate tailored biophysical and biochemical cues, thereby influencing stem cell differentiation and enhancing outcomes in regenerative medicine.[273.1] This interplay between mechanical and biochemical signals is vital for understanding how the ECM influences cellular behavior and fate.Applications In Regenerative Medicine
Use of ECM in Scaffolding
The use of extracellular matrix (ECM) in scaffolding for regenerative medicine is a rapidly evolving field that emphasizes the importance of biomaterials in tissue engineering. ECM scaffolds are designed to mimic the native ECM, providing both physical support and biochemical signals necessary for modulating various cell behaviors, including adhesion, proliferation, and differentiation.[326.1] These scaffolds can be composed of decellularized extracellular matrix (dECM), which retains bioactive molecules that are crucial for tissue homeostasis and regeneration.[327.1] The development of extracellular matrix (ECM)-based materials is a significant focus in regenerative medicine, as these materials aim to stimulate tissue formation or repair by recreating the functional and structural properties of native ECMs.[314.1] The ECM is a highly dynamic system that provides essential physical, biological, and chemical signals to the embedded cells, which is crucial for effective tissue regeneration.[318.1] Recent advancements have led to the creation of ECM-mimicking biomaterials with various biophysical and biochemical properties, enhancing their interaction with cells.[318.1] Additionally, the mechanical properties of these materials can be fine-tuned through the incorporation of crosslinkers, making them suitable for specific applications, such as organ-on-a-chip technologies.[319.1] This versatility underscores the ECM's role as nature's template for ideal biomaterials that guide tissue homeostasis and repair.[322.1] Extracellular matrix (ECM) scaffolds play a crucial role in tissue regeneration by serving as substitutes that allow cells to adhere, proliferate, and differentiate while the scaffold is gradually degraded and replaced by new tissue.[324.1] These scaffolds facilitate a constructive remodeling response in tissues through mechanisms that include relatively rapid and complete degradation, as well as the release of bioactive molecules that are resident within normal mammalian ECM and cryptic peptide molecules with diverse activities that promote the recruitment of endogenous stem and progenitor cells.[325.1] However, the clinical translation of next-generation ECM scaffold formulations faces predictable challenges, including issues related to manufacturing, regulatory pathways, surgical implantation, and the associated costs.[328.1]Cell-Derived Matrices in Therapy
Cell-derived matrices, particularly decellularized extracellular matrix (dECM) materials, have gained prominence in regenerative medicine due to their unique properties that closely mimic the native tissue environment. These materials exhibit low immunogenicity and provide a biomimetic microenvironment, which is crucial for promoting tissue repair and regeneration.[331.1] In clinical trials, dECM has demonstrated significant effectiveness; for instance, a study involving 120 chronic leg ulcer cases showed that 60% of patients treated with dECM achieved complete healing within 12 weeks, compared to only 35% in the standard treatment group.[330.1] The application of dECM extends to various therapeutic contexts, including wound healing products and surgical mesh devices, highlighting its versatility in clinical settings.[353.1] The biological scaffolds composed of ECM have been utilized to facilitate the repair and reconstruction of diverse tissues, although their clinical use may be constrained by the geometric and mechanical properties of the source tissue.[332.1] The three-dimensional structure of the ECM, which comprises various macromolecules such as collagen and proteoglycans, plays a vital role in supporting cell adhesion and influencing critical cellular behaviors like migration and differentiation.[333.1] Moreover, advancements in dECM technology have led to the development of biocompatible delivery systems for cells, drugs, and other therapeutic agents, further enhancing its application in regenerative therapies.[352.1] However, challenges remain in replicating the complexity of the native microenvironment, which can limit the regenerative capacity of current commercial matrices.[355.1] Despite these challenges, the potential of dECM biomaterials to stimulate in situ tissue repair through chemotactic effects is being explored, paving the way for innovative growth factor and cell-free tissue engineering strategies.[354.1] As research continues, the lessons learned from real-world applications of dECM will inform future developments in this promising field of regenerative medicine.In this section:
References
[1] Extracellular matrix - Wikipedia — In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM. There are many cell types that contribute to the development of the various types of extracellular matrix found in the plethora of tissue types. The extracellular matrix and cell adhesion, in Cells (eds Lewin B, Cassimeris L, Lingappa V, Plopper G).
[2] The Structure, Components, and Function of Extracellular Matrix — The composition of extracellular matrix (ECM) is tissue specific, however, its functions with respect to cellular adhesion, communication, and differentiation remain uniform irrespective of the change in composition. The extracellular matrix (ECM) acts as an adhesive that holds all the cells of a tissue in place.
[3] Extracellular Matrix: Definition, Function, Components - Biology Dictionary — Since the extracellular matrix is thick and mineralized despite its water rich content, it has the additional function of keeping the cells in a tissue separate and physically distinct. The extracellular matrix is mostly made up of a few key ingredients: water, fibrous proteins, and proteoglycans. The main fibrous proteins that build the extracellular matrix are collagens, elastins, and laminins. Unlike fibrous proteins, which will resist against stretching with the structures they form that actually lend the tissue tensile strength and rigidity, proteoglycans will resist against “squashing” or compressive forces. Unlike fibrous proteins, which will resist against stretching with the structures they form that actually lend the tissue tensile strength and rigidity, proteoglycans will resist against “squashing” or compressive forces.
[4] Extracellular Matrix - an overview | ScienceDirect Topics — 3.1.1 Overview. The extracellular matrix (ECM) is a dynamic three-dimensional structure that anchors and surrounds cellular compartments in tissues and organs. The ECM is composed of interconnected macromolecular assemblies that exist either as an interstitial matrix, as a special sheet-like structure known as a basement membrane, or as
[5] The Extracellular Matrix: an Overview - SpringerLink — Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series "Biology of Extracellular Matrix" provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix.
[6] The extracellular matrix: for tissue engineering - tissueandcells — The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineeringThe extracellular matrix is a structural support network made up of diverse proteins, sugars, and other components. It influences a wide number of cellular processes including migration, wound healing, and differentiation, all of which is of particular interest
[7] Engineered extracellular matrices: emerging strategies for decoupling ... — Cells simultaneously secrete new matrix proteins and remodel the existing extracellular matrix (ECM), giving rise to spatial and temporal heterogeneity across multiple length and time scales . Owing to this remarkable complexity, the structural and molecular mechanisms by which the ECM influences the behavior of single cells and multicellular
[8] The dynamics of cell-extracellular matrix interactions, with ... — For many years the extracellular matrix (ECM) was thought to serve only as a structural support for tissues. This began to change as multiple research groups observed differences in cell structure and organization, as well as changes in gene expression, when cells were cultured in the presence or absence of ECM components.
[11] Extracellular matrix constitution and function for tissue regeneration ... — The extracellular matrix (ECM) constituents vary greatly from tissue to tissue, with age and disease. The process of ECM construction is highly regulated during embryonic development and organ homeostasis but is impaired or deregulated during disease and in the elderly. To design effective therapeutic strategies for tissue repair and regeneration, it is crucial to know the changes that occur
[12] Extracellular Matrix Stiffness: Mechanotransduction and ... — The extracellular matrix (ECM) is a dynamic network providing mechanical and biochemical cues that regulate cellular behavior. ECM stiffness critically influences fibroblasts, the primary ECM producers, particularly in inflammation and fibrosis. This review explores the role of ECM stiffness in fibroblast-driven inflammation and tissue remodeling, focusing on the physicochemical and biological
[13] Effects of extracellular matrix viscoelasticity on cellular behaviour — Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels an …
[16] The Physical and Biochemical Properties of the Extracellular Matrix ... — Rather than merely providing structural information to cells, the extracellular matrix plays an instructive role in development and is critical for the maintenance of tissue homeostasis. ... and chemical entity that regulates tissue organization and cell behavior through a dynamic and reciprocal dialogue with the cellular constituents of the
[17] Extracellular matrix: A dynamic microenvironment for stem cell niche — Extracellular matrix (ECM) is a dynamic and complex environment characterized by biophysical, mechanical and biochemical properties specific for each tissue and able to regulate cell behavior. Stem cells have a key role in the maintenance and regeneration of tissues and they are located in a specific microenvironment, defined as niche.
[18] Cell-3D Matrix Interactions: Recent Advances and Opportunities — Biochemical or mechanical properties of the extracellular matrix governing cell-ECM interactions. (A) The specific molecules comprising the ECM can modulate cell behavior, e.g., via biochemical signals from collagens, elastin, fibronectin, proteoglycans, etc. (B) The concentration of each ECM component can alter cell interactions, e.g., different densities of collagen or proteoglycans.
[20] Cell-extracellular matrix mechanotransduction in 3D - Nature — Mechanical cues from the extracellular matrix (ECM) regulate cell fate and behaviour through cell-ECM mechanotransduction. Studies of cell-ECM mechanotransduction have largely focused on cells
[22] Modulating extracellular matrix stiffness: a strategic approach to ... — The interplay between extracellular matrix (ECM) stiffness and the tumor microenvironment is increasingly recognized as a critical factor in cancer progression and the efficacy of immunotherapy. 1.Extracellular matrix (ECM) stiffness plays a critical role in promoting cancer initiation and progression by regulating the malignant behaviors of cancer cells. Second, the review extensively discusses the effects of targeting ECM stiffness to enhance the efficacy of a range of immunotherapeutic strategies, including ICB therapy, adoptive cell therapy (ACT), oncolytic virus therapy (OVT), and therapeutic cancer vaccines (TCVs). In cancer cells, the methylation of the RASSF1A promoter triggers a sequence of events where increased expression of nuclear YAP1 and P4HA2 leads to enhanced collagen deposition in the ECM, thereby contributing to its increased stiffness .
[27] Tissue repair and the dynamics of the extracellular matrix — The extracellular matrix directs repair by regulating the behavior of the wide variety of cell types that are mobilized to the damaged area in order to rebuild the tissue. Acute inflammation, re-epithelialization, and contraction all depend on cell-extracellular matrix interactions and contribute to minimize infection and promote rapid wound
[28] Extracellular matrix: Structure and functions | Abcam — Integrins facilitate communication between cells and the extracellular matrix (ECM) by acting as transmembrane linkers that physically connect the ECM to the cytoskeleton within the cell. They also function as signal transducers, activating intracellular signaling pathways in response to ECM binding, thereby influencing cell survival, migration
[35] Post-translational modifications of the extracellular matrix are key ... — Each PTM results from a specific local physiological or pathobiological process. Identification of each modification to a tissue-specific protein may reveal a unique disease-specific biochemical marker. During cancer metastasis, the host tissue is extensively degraded and replaced by cancer-associated extracellular matrix (ECM) proteins.
[36] Passing the post: roles of posttranslational modifications in the form ... — The extracellular matrix (ECM) is central to the physiology of animal tissues, through its multifaceted roles in tissue structure, mechanical properties, and cell interactions, and by its cell-signaling activities that regulate cell phenotype and behavior. ... Post-translational modifications of the extracellular matrix are key events in cancer
[37] Modification of extracellular matrix proteins by oxidants and ... — The ECM comprises of multiple different protein species and sugar polymers, with both different isoforms and post-translational modifications (PTMs) providing a large variety of microenvironments that play a key role in determining tissue structure and health. ... This can in turn affect cell-matrix interactions and cellular function
[38] The Physical and Biochemical Properties of the Extracellular Matrix ... — In this chapter, we review the composition of the extracellular matrix and summarize data illustrating its importance in embryogenesis, tissue-specific development, and stem cell differentiation. However, it is now understood that the ECM is a biologically active component of all tissues that directs cell fate and influences tissue development and homeostasis (Fig. 1). The concept of “dynamic reciprocity” which maintains that the evolving ECM dictates cell and tissue fate which feedback to modulate ECM composition and organization represents a critical concept in developmental biology (Bissell, Hall, & Parry, 1982; Paszek & Weaver, 2004). The ECM regulates embryogenesis, tissue-specific development, and stem cell fate by binding cellular receptors and activating ion channels to initiate intracellular signaling and gene transcription, by controlling the availability, activation, and presentation of soluble ligands, and by altering cellular tension.
[47] Drug discovery in the extracellular matrix - ScienceDirect — Extracellular matrix drug discovery in an evolutionary context Extracellular matrix is a key characteristic of all metazoan organisms . The types of matrices formed, however, have been expanded in vertebrates to produce novel tissues, such as bone, tendon and cartilage.
[48] History of extracellular matrix: a personal view - PubMed — With the discovery of cells in connective tissue, the cellular theory became accepted as the basis of life in about 1850. ... Material outside cells, but presumably made by cells, was recognized as the extracellular matrix. In the period from 1930 to 1975, the components of extracellular matrix were characterized by physical chemical, chemical
[49] History of extracellular matrix: a personal view - PubMed — History of extracellular matrix: a personal view - PubMed Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Your saved search Name of saved search: History of extracellular matrix: a personal view History of extracellular matrix: a personal view Since 1975, molecular and cell biological techniques have shown that the extracellular matrix is not the passive residence of cells but is highly interactive and plays a major role in health and disease. Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins. Halper J, et al. [The connective tissues, from the origin of the concept to its "Maturation" to extracellular matrix. Labat-Robert J, et al. Uitto J, et al. Huang J, et al. Extracellular Matrix*
[50] The Charming World of the Extracellular Matrix: A Dynamic and ... — The Long History of the Extracellular Matrix. In the scientific community, the ECM is considered the most complex structural organization of tissues in organisms. To date, the paradigm "no cells, no ECM" persists, but it was a long way to go to prove it, as the cells were discovered even thousands of years later than the ECM . Around the
[53] Cell response to extracellular matrix viscous energy dissipation ... - AAAS — The extracellular matrix (ECM) is a proteoglycan-based hydrogel supporting cells in biological tissues. Structural and biochemical signals from the ECM are essential for cell homeostasis, adhesion, migration, proliferation, and differentiation ().However, it is now well-established that the mechanical properties of the ECM also affect the activity and fate of cells to a large extent (2, 3).
[55] New advances in probing cell-extracellular matrix interactions — The extracellular matrix (ECM) provides structural and biochemical support to cells within tissues. An emerging body of evidence has established that the ECM plays a key role in cell mechanotransduction - the study of coupling between mechanical inputs and cellular phenotype - through either mediating transmission of forces to the cells, or presenting mechanical cues that guide cellular
[56] The Physical and Biochemical Properties of the Extracellular Matrix ... — In this chapter, we review the composition of the extracellular matrix and summarize data illustrating its importance in embryogenesis, tissue-specific development, and stem cell differentiation. However, it is now understood that the ECM is a biologically active component of all tissues that directs cell fate and influences tissue development and homeostasis (Fig. 1). The concept of “dynamic reciprocity” which maintains that the evolving ECM dictates cell and tissue fate which feedback to modulate ECM composition and organization represents a critical concept in developmental biology (Bissell, Hall, & Parry, 1982; Paszek & Weaver, 2004). The ECM regulates embryogenesis, tissue-specific development, and stem cell fate by binding cellular receptors and activating ion channels to initiate intracellular signaling and gene transcription, by controlling the availability, activation, and presentation of soluble ligands, and by altering cellular tension.
[60] Pooled extracellular receptor-ligand interaction screening using CRISPR ... — Extracellular interactions between cell surface receptors are necessary for signaling and adhesion but identifying them remains technically challenging. We describe a cell-based genome-wide approach employing CRISPR activation to identify receptors for a defined ligand. We show receptors for high-af …
[62] Role of the Extracellular Matrix in Cancer: Insights into Tumor ... — The extracellular matrix (ECM) serves not only as a structural scaffold but also as an active regulator of cancer progression, profoundly influencing tumor behaviour and the tumor microenvironment (TME). This review focuses into the pivotal role of ECM alterations in facilitating tumor metastasis and explores therapeutic strategies aimed at counteracting these changes. We analyse targeted
[64] The extracellular matrix as hallmark of cancer and metastasis: From ... — The extracellular matrix (ECM) is essential for cell support during homeostasis and plays a critical role in cancer. Although research often concentrates on the tumor's cellular aspect, attention is growing for the importance of the cancer-associated ECM. Biochemical and physical ECM signals affect tumor formation, invasion, metastasis, and therapy resistance. Examining the tumor
[96] Cell-3D Matrix Interactions: Recent Advances and Opportunities — Recent research advances in characterizing cell-matrix interactions include detailed descriptions of hundreds of ECM and associated molecules, their complex intermolecular interactions in development and disease, identification of distinctive modes of cell migration in different 3D ECMs, and new insights into mechanisms of organ formation. The interactions of cells with the 3D extracellular matrix (ECM) (see Glossary) play crucial roles during cell migration and organ formation in embryonic development, differentiation, adult tissue homeostasis, and pathogenesis of diseases such as fibrosis and cancer. (2016) Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs. Proc Natl Acad Sci U S A 113, 14043–14048 [DOI] [PMC free article] [PubMed] [Google Scholar] (2019) Adaptive F-actin polymerization and localized ATP production drive basement membrane invasion in the absence of MMPs. Dev Cell 48, 313–328 e318 [DOI] [PMC free article] [PubMed] [Google Scholar]
[102] Stiff extracellular matrix drives the differentiation of mesenchymal ... — The mechanical properties of the extracellular matrix (ECM) regulate stem cell fate during tissue development, regeneration, and disease .ECM stiffness has become one of the most concerning microenvironmental mechanical cues in tissue engineering .Mesenchymal stem cells (MSCs) are readily available and exhibit multi-lineage differentiation potential, which has been widely used in
[105] Extracellular matrix-derived biomaterials in engineering cell function ... — Recent technological advances in decellularizing tissue and isolating cells allow the creation of functional complex biomaterials that take advantage of ECM proteins in their natural form. ... Dyke M, 2009. The influence of extracellular matrix derived from skeletal muscle tissue on the proliferation and differentiation of myogenic progenitor
[106] Extracellular matrix-based materials for regenerative medicine — The extracellular matrix is nature's template for an ideal biomaterial to guide tissue homeostasis and repair. In this Review, matrix-mimicking biomaterials and decellularized matrices are
[107] Biochemical and biophysical cues of the extracellular matrix modulates ... — Biochemical and Biophysical Cues of The Extracellular Matrix Modulates Stem Cell Fate: Progress and Prospect in Extracellular Matrix Mimicking Biomaterials - ScienceDirect Biochemical and Biophysical Cues of The Extracellular Matrix Modulates Stem Cell Fate: Progress and Prospect in Extracellular Matrix Mimicking Biomaterials Engineered biomaterials to replicate the properties of the ECM are discussed along with the incorporation of tailored biophysical and biochemical cues into scaffolds and biomaterials to modulate stem cell fate. Overall, this review underscores the innovative applications of ECM mimicking biomaterials in biomedical engineering, emphasizing their transformative potential to modulate stem cell fate and advance regenerative medicine. No articles found. For all open access content, the Creative Commons licensing terms apply.
[113] Modulating extracellular matrix stiffness: a strategic approach to ... — The interplay between extracellular matrix (ECM) stiffness and the tumor microenvironment is increasingly recognized as a critical factor in cancer progression and the efficacy of immunotherapy. 1.Extracellular matrix (ECM) stiffness plays a critical role in promoting cancer initiation and progression by regulating the malignant behaviors of cancer cells. Second, the review extensively discusses the effects of targeting ECM stiffness to enhance the efficacy of a range of immunotherapeutic strategies, including ICB therapy, adoptive cell therapy (ACT), oncolytic virus therapy (OVT), and therapeutic cancer vaccines (TCVs). In cancer cells, the methylation of the RASSF1A promoter triggers a sequence of events where increased expression of nuclear YAP1 and P4HA2 leads to enhanced collagen deposition in the ECM, thereby contributing to its increased stiffness .
[114] Extracellular matrix as a driver of progressive fibrosis — When pathological changes in the ECM lead to impairment of organ function, we use the term "fibrosis." In this Review, we differentiate fibrosis initiation from progression and focus primarily on progressive lung fibrosis impairing organ function. A comprehensive tissue atlas would combine — at both the micron and millimeter scale of resolution — static and dynamic mechanical measurements, data regarding ECM composition and organization, cell identity, cell differentiated state, and cell biology (e.g., proliferation markers, signaling footprints). With such a data set, investigators would be positioned to generate testable models that pinpoint targetable pathways critical to fibrosis progression based on (a) the precise mechanical properties a cell is sensing, (b) the ECM components a cell is interacting with, and (c) the resulting cell biology as a function of those inputs.
[115] Fibrosis and cancer: A strained relationship - PMC - PubMed Central (PMC) — Tumor fibrosis by contrast is characterized by chronic inflammation, elevated numbers of contractile myofibroblasts that secrete abundant ECM proteins and remodeling enzymes that reorganize, cross-link and stiffen the matrix, and cytokines and growth factors that stimulate tumor cell proliferation and invasion yielding a markedly different stroma (Fig. 2) [21–26]. , Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines, Cancer Res. 71 (15) (2011) 5075–5080. , Molecular characterization of the tumor microenvironment in breast cancer, Cancer Cell 6 (1) (2004) 17–32. , Tumor cell invasion can be blocked by modulators of collagen fibril alignment that control assembly of the extracellular matrix, Cancer Res. 76 (14) (2016) 4249–4258.
[116] Extracellular matrix as a driver of progressive fibrosis - PMC — However, the studies cited above, which track YAP activity in the context of ECM stiffness, dimensionality, viscoelasticity, cyclic stretch, and cell-cell interactions, demonstrate the importance of accounting for multiple parameters when constructing a model of the in vivo biology of progressive fibrosis. The ECM in the fibrogenic niche is compartmentalized, with its composition and mechanical properties organized in a manner that nurtures, supports, and guides all of the cells that mediate fibrosis progression: self-renewing MPCs, actively proliferating transit-amplifying cells, and pathological myofibroblasts that persist and actively secrete ECM. With such a data set, investigators would be positioned to generate testable models that pinpoint targetable pathways critical to fibrosis progression based on (a) the precise mechanical properties a cell is sensing, (b) the ECM components a cell is interacting with, and (c) the resulting cell biology as a function of those inputs.
[133] The matrix in cancer - Nature Reviews Cancer — The extracellular matrix is altered in many ways during tumour progression at both primary and secondary sites. In addition to biochemical changes, the biophysical properties of the matrix are
[134] Concepts of extracellular matrix remodelling in tumour progression and ... — Thus, it is not surprising that cancer cells and tumour-associated stromal cells modify all four ECM remodelling mechanisms, creating a cancer-supporting matrix that actively contributes to the pathology of the tumour (Fig. 2)12. a, b Tumour-derived factors activate stromal cells which differentiate into cancer-associated fibroblasts (CAFs) leading to the secretion and deposition of large amounts of ECM components along with the cancer cells. The tumour-derived activation factors induce the differentiation of stromal cells towards so-called cancer-associated fibroblasts (CAFs), which function as myofibroblasts and remodel the ECM to support tumour growth17,20,23,24. Stromal cells in the pre-metastatic niche are activated by tumour-derived factors and myofibroblasts remodel the ECM, for example, by the deposition of fibronectin, tenascin C, osteopontin, and versican depending on tissue context.
[141] Biology of the Extracellular Matrix: An Overview - PMC — The chemical cues are provided by ECM components, especially the adhesive proteins such as fibronectin, integrin and non-integrin receptors, as well as growth factors and associated signaling molecules. These interactions are involved in the formation of supramolecular assemblies such as collagen fibrils and elastic fibers, in tissue architecture, and in cell-matrix interactions that regulate cell growth and behavior. ECM/integrin interaction within the stem cell niche contributes to three main functions: (1) Cell-matrix anchorage, in which integrin-mediated cell adhesion physically anchors the stem cell to ECM proteins. , growth factors and their receptors; , morphogens and their receptors; , extracellular matrix; , α and β integrin subunits; , cytoskeletal filaments; SC: stem cell.
[143] Extracellular Matrix: Definition, Function, Components - Biology Dictionary — Since the extracellular matrix is thick and mineralized despite its water rich content, it has the additional function of keeping the cells in a tissue separate and physically distinct. The extracellular matrix is mostly made up of a few key ingredients: water, fibrous proteins, and proteoglycans. The main fibrous proteins that build the extracellular matrix are collagens, elastins, and laminins. Unlike fibrous proteins, which will resist against stretching with the structures they form that actually lend the tissue tensile strength and rigidity, proteoglycans will resist against “squashing” or compressive forces. Unlike fibrous proteins, which will resist against stretching with the structures they form that actually lend the tissue tensile strength and rigidity, proteoglycans will resist against “squashing” or compressive forces.
[144] Extracellular matrix: Structure and functions | Abcam — The extracellular matrix (ECM) is a dynamic, three-dimensional (3D) network of more than 300 macromolecules, including proteins, glycoproteins, and polysaccharides, that surrounds and supports cells in tissues and organs. As they regulate the composition and structure of the ECM around cells, they have important roles in several physiological processes like angiogenesis, tissue development, and wound healing. The interstitial matrix and basement membrane represent distinct ECM types, with the interstitial matrix providing structural integrity within connective tissues and the basement membrane offering a tightly organized network for cell attachment and filtration in epithelial and endothelial tissues. The ECM provides a 3D scaffold that maintains the structural integrity of tissues while offering biochemical signals essential for stem cell attachment, survival, and function.
[146] The role of fibronectin in mediating cell migration — Fibronectin (FN) is a major extracellular matrix (ECM) protein involved in a wide range of physiological processes, including cell migration. These FN-mediated cell migration events are essential to processes such as wound repair, cancer metastasis, and vertebrate development. This review synthesizes mainly current literature to provide an overview of the mechanoregulatory role of FN-mediated
[147] Fibronectin: Molecular Structure, Fibrillar Structure and ... — The extracellular matrix (ECM) plays a key role as both structural scaffold and regulator of cell signal transduction in tissues. In times of ECM assembly and turnover, cells upregulate assembly of the ECM protein, fibronectin (FN). FN is assembled by cells into viscoelastic fibrils that can bind upward of 40 distinct growth factors and cytokines. These fibrils play a key role in assembling a
[148] Fibronectin - an overview | ScienceDirect Topics — Fibronectin is one of the well-known adhesive proteins that promote cell adhesion. Recent studies using synthetic peptides have demonstrated the important binding sites in fibronectin for integrin families and proteoglycans (Table 1). Fig. 2 shows one current view of fibronectin in the role of cell-matrix ligand. Obviously several features of this model remain uncertain. However, the model of
[149] Collaboration of Fibronectin Matrix with other Extracellular Signals in ... — Tissue formation and cell differentiation depend on a properly assembled extracellular matrix (ECM). Fibronectin is a key constituent of the pericellular ECM, forming essential connections between cell surface integrin receptors and structural components
[150] (PDF) Fibronectin: Molecular Structure, Fibrillar Structure and ... — FBN facilitates cell adherence, spreading, migration, proliferation, and differentiation Fibronectin plays a crucial role in controlling how cells adhere to one another, disseminate, migrate
[151] Fibronectins, Their Fibrillogenesis, and In Vivo Functions - PMC — Fibronectin (FN) is a multidomain protein with the ability to bind simultaneously to cell surface receptors, collagen, proteoglycans, and other FN molecules. Many of these domains and interactions are also involved in the assembly of FN dimers into
[191] Extracellular Matrix in Development and Disease - PMC — A common thread uniting the topics is the essential nature that the matrix plays in normal development and pathophysiology. Providing new knowledge will lead us to improved diagnostics, preventions to disease progression, and therapeutic strategies for repair and regeneration of tissues.
[192] Extracellular Matrix: The driving force of mammalian diseases — Human malaises including connective tissue disorders, muscular dystrophy, fibrosis, and cancer are all extracellular matrix-driven diseases. We will start our journey by defining the role of the ECM in connective tissue disorders where we can appreciate the necessity for a working matrix by noting the existence of the many types of skin, bone, and cartilaginous diseases that can be attributed to defective ECM components (Fig. 1). Fibrosis is a damaging process that can occur due to excess formation of connective tissue in response to injury , likely due to a combination of factors such as a disproportionate activity of matrix enzymes (i.e. MMPs, ADAMTS) that causes matrix degradation and re-organization as well as hyperactive ligand-mediated receptor signaling, most prevalently via TGF-β .
[193] Role of Extracellular Matrix in Development and Cancer Progression - MDPI — The immense diversity of extracellular matrix (ECM) proteins confers distinct biochemical and biophysical properties that influence cell phenotype. The ECM is highly dynamic as it is constantly deposited, remodelled, and degraded during development until maturity to maintain tissue homeostasis. The ECM's composition and organization are spatiotemporally regulated to control cell behaviour
[195] The role of extracellular matrix in angiogenesis: Beyond adhesion and ... — The native cell microenvironment, governed by the composition, organization, mechanical dynamics, and signaling regulators of the ECM, plays a pivotal role in angiogenesis .Previously considered as a static structural component, the ECM has recently gained increased recognition for its influence on vascular network formation, maturation, and the maintenance of vasculature [, , [13
[199] The Extracellular Matrix In Development and Morphogenesis: A Dynamic ... — The extracellular matrix (ECM) is synthesized and secreted by embryonic cells beginning at the earliest stages of development. Our understanding of ECM composition, structure and function has grown considerably in the last several decades and this knowledge has revealed that the extracellular microenvironment is critically important for cell growth, survival, differentiation and morphogenesis. Several key observations culminating in the discovery of the integrins (and other ECM receptors) in the mid 1980s, altered forever our view of the ECM and its involvement in normal physiology and homeostasis, disease progression and development (Dzamba et al., 2001). doi: 10.1158/0008-5472.CAN-04-1234. doi: 10.1038/304315a0. doi: 10.1016/0012-1606(82)90228-7. doi: 10.1023/A:1025321105691. doi: 10.1038/35047564. doi: 10.1016/s0012-1606(03)00187-8. doi: 10.1016/s1534-5807(04)00063-2. doi: 10.1038/35011077. doi: 10.1016/0012-1606(80)90402-9. doi: 10.1158/0008-5472.CAN-07-2673. doi: 10.1038/415168a. doi: 10.1007/s10439-005-3037-7.
[200] The extracellular matrix in development - PubMed — 1 Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892-4370, USA kenneth.yamada@nih.gov david.cruzwalma@nih.gov. As the crucial non-cellular component of tissues, the extracellular matrix (ECM) provides both physical support and signaling regulation to cells. In addition, we discuss how the ECM helps to regulate tissue morphology during embryonic development by governing key elements of cell shape, adhesion, migration and differentiation. These types of ECM help to direct cell and tissue shape during morphogenesis in development by influencing cell adhesion (A), migration (B), morphology (C) and differentiation (D). Extracellular matrix dynamics in cell migration, invasion and tissue morphogenesis. 10.1016/j.biomaterials.2015.05.030 - DOI - PubMed 10.1016/j.ajhg.2019.09.005 - DOI - PMC - PubMed
[202] Extracellular matrix in cancer progression and therapy - PMC — Keywords: cancer invasion, cancer metabolism, cancer progression, cancer therapy, cell-ECM interaction, extracellular matrix, metastasis During cancer progression, alterations in tumor cell – ECM interactions drive malignant transformation, invasion, and metastasis, as well as treatment resistance , , , , , . These excess ECM molecules come from the tumor cells and cancer-associated fibroblasts (CAFs) . Adding to the mix, tumor-associated hypoxia induces lysyl oxidase expression , along with other ECM modifying enzymes, resulting in the fibrillar collagen crosslinking within the ECM and the synergy of biophysical and biochemical changes that allow cancer cells to more efficaciously invade and metastasize . doi: 10.1016/j.cell.2016.01.043. doi: 10.4103/2153-3539.139707. doi: 10.1517/14728222.9.3.491. doi: 10.1158/0008-5472.can-06-0482. doi: 10.1038/s41568-018-0016-5. doi: 10.1038/s41573-019-0024-5. doi: 10.1038/s41568-020-00327-9. doi: 10.1186/1471-2407-12-4. doi: 10.1038/s41467-018-06893-9. doi: 10.1016/j.cell.2017.10.044.
[203] Concepts of extracellular matrix remodelling in tumour ... - Nature — Thus, it is not surprising that cancer cells and tumour-associated stromal cells modify all four ECM remodelling mechanisms, creating a cancer-supporting matrix that actively contributes to the pathology of the tumour (Fig. 2)12. a, b Tumour-derived factors activate stromal cells which differentiate into cancer-associated fibroblasts (CAFs) leading to the secretion and deposition of large amounts of ECM components along with the cancer cells. The tumour-derived activation factors induce the differentiation of stromal cells towards so-called cancer-associated fibroblasts (CAFs), which function as myofibroblasts and remodel the ECM to support tumour growth17,20,23,24. Stromal cells in the pre-metastatic niche are activated by tumour-derived factors and myofibroblasts remodel the ECM, for example, by the deposition of fibronectin, tenascin C, osteopontin, and versican depending on tissue context.
[204] Extracellular matrix and its therapeutic potential for cancer treatment — Lung cancer cells also express more PD-L1 in response to ECM stiffness to shut down the anti-tumor immune response mediated by CD8+ T cells218. J. Hyaluronan-CD44 interaction promotes oncogenic signaling, microRNA functions, chemoresistance, and radiation resistance in cancer stem cells leading to tumor progression. R. The human hyaluronan receptor RHAMM is expressed as an intracellular protein in breast cancer cells. Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells.
[205] The Functional Role of Extracellular Matrix Proteins in Cancer — We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells. 342.Koskimaki J.E., Karagiannis E.D., Tang B.C., Hammers H., Watkins D.N., Pili R., Popel A.S. Pentastatin-1, a Collagen IV Derived 20-Mer Peptide, Suppresses Tumor Growth in a Small Cell Lung Cancer Xenograft Model. Degradation of Tenascin-C and Activity of Matrix Metalloproteinase-2 Are Associated with Tumor Recurrence in Early Stage Non-Small Cell Lung Cancer. The Promoting Effect of the Extracellular Matrix Peptide TNIIIA2 Derived from Tenascin-C in Colon Cancer Cell Infiltration. 360.Blood C.H., Sasse J., Brodt P., Zetter B.R. Identification of a Tumor Cell Receptor for VGVAPG, an Elastin-Derived Chemotactic Peptide.
[206] Role of the Extracellular Matrix in Cancer: Insights into Tumor ... — The extracellular matrix (ECM) is pivotal in cancer progression, influencing tumor growth, metastasis, and therapy resistance. ... Variations arise from differences in sugar composition, ... The dysregulated Hedgehog signaling has been implicated in the initiation and progression of several cancer types, including basal cell carcinoma
[207] Editorial: The role of the extracellular matrix in tumor progression ... — Future studies focusing on mechanistic validation of these matrix-related biomarkers are imperative in a large patient cohort of different solid cancers. Further matrix interactions with other TME cell types (immune cells, fibroblasts, etc.) will provide greater insights in understanding the role of ECM modeling during cancer progression.
[208] Genetic Disorders of the Extracellular Matrix - PMC — Mutations in the genes for extracellular matrix (ECM) components cause a wide range of genetic connective tissues disorders throughout the body. The elucidation of mutations and their correlation with pathology has been instrumental in understanding the roles of many ECM components.
[210] Genetic diseases of connective tissues: cellular and extracellular ... — The extracellular matrices (ECMs) of connective tissues are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited disorders.
[212] Progress in biomaterials inspired by the extracellular matrix — Progress in biomaterials inspired by the extracellular matrix - ScienceDirect Inspired by the extracellular matrix (ECM), biomaterials have emerged as promising strategies in the biomedical research and engineering domain, offering unique characteristics for tissue regeneration, drug delivery, therapeutic interventions, and cellular investigations. Furthermore, by mimicking the structural composition of ECM components, ECM-inspired biomaterials exhibit varying degrees of ECM functionalization, including providing structural support, cell adhesion, signal transduction, mitigating immune responses, and tissue remodeling. Biomaterials inspired by the extracellular matrix (ECM) offer unique properties for tissue regeneration, drug delivery, and cellular investigations. Advancements in ECM-inspired biomaterials have promising applications in tissue engineering, regenerative medicine, and drug delivery. Next article in issue No articles found. For all open access content, the relevant licensing terms apply.
[235] Mechanotransduction and extracellular matrix homeostasis — As detailed below, mechanical homeostasis thus involves ECM constituents such as the collagens and elastin that support and transmit loads; transmembrane receptors for these constituents, primarily the integrins that connect extracellular and intracellular structures plus their associated linker proteins (such as talin and vinculin) that connect the receptors to the cytoskeleton; and actin filaments, non-muscle myosin, and associated proteins that constitute the cytoskeleton and transmit mechanical loads or signals within the cell (Fig. 1). In particular, cells interact mechanically with the ECM via heterodimeric transmembrane receptors called integrins, which in turn interact with intracellular signaling molecules (including focal adhesion kinase (FAK) and Src) and physically connect to cytoskeletal actin via a host of linker proteins (including talin, vinculin, filamin, the ILK-PINCH-parvin complex, and α-actinin).
[237] Mechanotransduction and extracellular matrix homeostasis — Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix (ECM) that are fundamental to cellular and tissue health. The mechanosens …
[239] 2. Physical Properties of Extracellular Matrix - National Center for ... — 2.1.2. Stem Cells and Matrix Elasticity In Vivo. Stiffness of the adjacent tissue affects stem cell fate in vivo when the cell exits its niche and starts to participate in regenerative process . Stem cells tend to proliferate, migrate towards the injured site, and differentiate to the relevant cell type, adoptive to stiffness of the substrate.
[242] The extracellular matrix viscoelasticity as a regulator of cell and ... — It has long been appreciated that the extracellular matrix (ECM) mechanical properties are altered in several circumstances, including during development and pathologies such as cancer and fibrosis .More recently, research efforts have focused on identifying how these changes in ECM mechanical properties regulate tissue responses .Among the different mechanical properties, research
[243] The extracellular matrix in development - PMC — After first introducing principles of cell-ECM interactions, we focus primarily on recently published examples to discuss how the ECM helps to direct developing tissues by influencing cell adhesion, migration, shape and differentiation (Fig. 1A-D). These types of ECM help to direct cell and tissue shape during morphogenesis in development by influencing cell adhesion (A), migration (B), morphology (C) and differentiation (D). Cells use these adhesions to attach directly either to anchoring ligands of the ECM interstitial matrix (e.g. fibrous collagens, fibronectin and vitronectin) or to other glycoproteins in the basement membrane (e.g. laminin or network collagens) (Table 1; Fig. 1A) (Frantz et al., 2010; Hynes and Yamada, 2012). 10.1016/j.cell.2007.08.006 [DOI] [PubMed] [Google Scholar]
[245] Extracellular matrix dynamics: A key regulator of cell migration across ... — The extracellular matrix (ECM) is a complex 3-dimensional (3D) meshwork of proteins that provides structural support to cells, tissues, organs, and organisms . In addition, the ECM provides physical, mechanical, and chemical cues that regulate proliferation, migration, differentiation, and function during development, tissue morphogenesis, and homeostasis . Thus, alterations in ECM
[247] Extracellular Matrix Components and Mechanosensing Pathways in Health ... — Glycosaminoglycans (GAGs) and proteoglycans (PGs) are essential components of the extracellular matrix (ECM) with pivotal roles in cellular mechanosensing pathways. GAGs, such as heparan sulfate (HS) and chondroitin sulfate (CS), interact with various cell surface receptors, including integrins and …
[248] Mechanotransduction: use the force(s) - PMC - PubMed Central (PMC) — 2 Chemical & Biological Engineering, Princeton University, 303 Hoyt Laboratory ... cell cytoskeleton in responding to physical cues such as the rigidity of its environment is one of the most studied examples of mechanotransduction. ... durotaxis is thought to be important for tissue formation during embryogenesis, or the migration of cells
[250] Cell-Extracellular Matrix Mechanobiology: Forceful Tools and Emerging ... — Extracellular biophysical cues have a profound influence on a wide range of cell behaviors, including growth, motility, differentiation, apoptosis, gene expression, adhesion, and signal transduction. Cells not only respond to definitively mechanical cues from the extracellular matrix (ECM) but can also sometimes alter the mechanical properties of the matrix and hence influence subsequent
[266] Extracellular Matrix Components and Mechanosensing Pathways in Health ... — Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease - PubMed Glycosaminoglycans (GAGs) and proteoglycans (PGs) are essential components of the extracellular matrix (ECM) with pivotal roles in cellular mechanosensing pathways. Keywords: cancer; glycosaminoglycans; glypican; inflammation; mechanosensing; mechanotransduction; proteoglycans; syndecans. Figure: https://doi.org/10.6084/m9.figshare.26963677.v2 (accessed on 9 September 2024). Figure: https://doi.org/10.6084/m9.figshare.26983060.v1 (accessed on 12 September 2024). ECM fiber alignment and fiber cross-linking together with the secretion of growth factors (GFs), cytokines, mitogens, and enzymes (MMPs) by cancer-associated fibroblasts (brown cells) and immune cells (green cells) lead to modulation of mechanosensing and mechanotransduction pathways (receptors, signaling molecules, and cytoskeletal proteins). - DOI - PubMed - DOI - PMC - PubMed - DOI - PMC - PubMed - DOI - PMC - PubMed
[267] Mechanotransduction Pathways Linking the Extracellular Matrix to the ... — Several molecules cooperate in a complex network to perform cell mechanotransduction, which is to translate the mechanical signal into biochemical pathways. Herein, we present a review of the structure and functions of key molecules involved in cell mechanotransduction during integrin-mediated cell-ECM adhesion, and mechanisms by which this
[268] Mechanotransduction pathways linking the extracellular matrix to the ... — Cells contain several mechanosensing components that transduce mechanical signals into biochemical cascades. During cell-ECM adhesion, a complex network of molecules mechanically couples the extracellular matrix (ECM), cytoskeleton, and nucleoskeleton. The network comprises transmembrane receptor pr …
[269] Mechanisms of Mechanotransduction: Developmental Cell — One proposed mechanotransduction mechanism involves effects of strain on the actin cytoskeleton that results in c-Src activation (Han et al., 2004a). The actin filament-associated protein (AFAP-110), which is abundant in lung epithelial cells and fibroblasts, can bind and activate c-Src.
[272] Extracellular Matrix Regulation of Stem Cell Fate — Stem cell differentiation is orchestrated by an ever-changing extracellular milieu, which varies in biochemical and mechanical composition in a spatio-temporal manner. Careful material design and experimental approaches are necessary for truly uncovering the interplay between physical and chemical cues that are present in the natural ECM (Fig. 1). Engineering synthetic analogs allows for the
[273] Biochemical and biophysical cues of the extracellular matrix modulates ... — Biochemical and Biophysical Cues of The Extracellular Matrix Modulates Stem Cell Fate: Progress and Prospect in Extracellular Matrix Mimicking Biomaterials - ScienceDirect Biochemical and Biophysical Cues of The Extracellular Matrix Modulates Stem Cell Fate: Progress and Prospect in Extracellular Matrix Mimicking Biomaterials Engineered biomaterials to replicate the properties of the ECM are discussed along with the incorporation of tailored biophysical and biochemical cues into scaffolds and biomaterials to modulate stem cell fate. Overall, this review underscores the innovative applications of ECM mimicking biomaterials in biomedical engineering, emphasizing their transformative potential to modulate stem cell fate and advance regenerative medicine. No articles found. For all open access content, the Creative Commons licensing terms apply.
[276] Age-Related Changes in Extracellular Matrix - Springer — Abstract Extracellular matrix (ECM) is an extracellular tissue structure that, in addition to mechanical support to the cell, is involved in regulation of many cellular processes, including chemical transport, growth, migration, differentiation, and cell senescence. Age-related changes in the structure and composition of the matrix and increase of ECM stiffness with age affect functioning of
[277] A glitch in the matrix: Age-dependent changes in the extracellular ... — Age-related changes in the extracellular matrix (ECM) prime future sites of metastasis. When cancer cell "seeds" escape the primary tumor site, they are more likely to grow at a distant "soil" site they deem favorable. Normally, our organs have pliable ECM, with a balance of fibronectin, collagen, elastin, and overall homeostasis.
[278] Impaired angiogenesis in ageing: the central role of the extracellular ... — Each step in angiogenesis is regulated by the extracellular matrix (ECM). Accumulating evidence indicates that ageing-related changes in the ECM driven by cellular senescence lead to a reduction in neovascularisation, reduced microvascular density, and an increased risk of tissue ischaemic injury. These changes can lead to health events that have major negative impacts on quality of life and
[279] Longevity-Promoting Pathways and Transcription Factors Respond to and ... — We propose that modulation of these pathways increases lifespan and protects from age-related diseases in part due to their effects on extracellular matrix remodeling. Therefore, to successfully treat age-related diseases, it is necessary to better understand the connection between extracellular matrix components and longevity pathways.
[280] Fibroageing: An ageing pathological feature driven by dysregulated ... — Systemic inflammation, known as inflammageing, increases as a consequence of ageing contributing to age-related morbidities. But also, persistent and uncontrolled activation of fibrotic pathways, with excessive accumulation of extracellular matrix (ECM) and organ dysfunction is markedly more frequent in the elderly.
[281] Influence of exercise and aging on extracellular matrix composition in ... — Although exercise promotes ECM reorganization and stem cell accumulation, aging is associated with dense ECM deposition and loss of stem cell function resulting in reduced regenerative capacity and strength.
[285] Age related changes of the extracellular matrix and stem cell ... — Aging is characterized by reduced tissue and organ function, regenerative capacity, and accompanied by a decrease in tissue resident stem cell numbers and a loss of potency. The impact of aging on stem cell populations differs between tissues and depends on a number of non cell-intrinsic factors, in …
[287] The role of matrix metalloproteinases in aging: Tissue remodeling and ... — In this review, we will discuss how MMPs and other proteases alter ECM composition and mechanical properties in aging, thereby affecting stem cell niches and the development of senescent phenotypes. Consequently, we will highlight some mechanisms by which an aged ECM modulates its environment by affecting critical cellular compartments, such as the stem cell pool or the number of senescent cells, in the development of aging and age-related diseases. In this section, we will summarize the principal changes that occur in ECM structure and organization during aging in different tissues, highlighting the role of proteases such as MMPs in these processes. K. Kessenbrock, G.J. Dijkgraaf, D.A. Lawson, L.E. Littlepage, P.
[288] Age related changes of the extracellular matrix and stem cell ... — Age related changes in ECM not only mediate cell proliferation, differentiation, inflammation and apoptosis, but they also impact on recruitment, differentiation, and functional integration of stem and tissue specific progenitor cells. We have analyzed the interplay between matrix formation and stem cell senescence in a 3-dimensional (3D) MSC
[314] Therapeutic Applications of Extracellular Matrix - PMC — As such, a current emphasis in regenerative medicine is the development of ECM-based materials that can stimulate tissue formation or repair by recreating the functional and structural properties of native ECMs. 9 The focus of this forum issue is to highlight several of the recent advances made in developing wound care products and treatment
[318] Static and Dynamic: Evolving Biomaterial Mechanical Properties to ... — The extracellular matrix (ECM) is a highly dynamic system that constantly offers physical, biological, and chemical signals to embraced cells. ... In recent years, ECM‐mimicking biomaterials with various biophysical or biochemical properties have been developed. The mechanical properties of these materials, such as stiffness, viscosity
[319] Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue ... — The mechanical properties of the gel can be tuned by adding crosslinkers (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and n-hydroxysuccinimide) that makes collagen an attractive bio-ink for organ-on-a-chip applications . Fibrin has been used in maintaining the 3D shape of the printed constructs due to its rapid gelation properties.
[322] Extracellular matrix-based materials for regenerative medicine — The extracellular matrix is nature's template for an ideal biomaterial to guide tissue homeostasis and repair. In this Review, matrix-mimicking biomaterials and decellularized matrices are
[324] The Overview of Porous, Bioactive Scaffolds as Instructive Biomaterials ... — Many researchers used to generate porous scaffolds for tissue regeneration where the scaffold acts as an extracellular matrix (ECM) substitute for cells allowing them to adhere, proliferate, and to differentiate while the scaffold is gradually degraded and replaced by a new tissue. ... the controlled release of bioactive molecules is still a
[325] Extracellular Matrix as a Bioscaffold for Tissue Engineering — The mechanisms by which ECM scaffolds facilitate a constructive remodeling response in tissues are partially understood and include relatively rapid and complete degradation, the release of bioactive molecules that are resident within normal mammalian ECM, and the release of bioactive cryptic peptide molecules with diverse activities promoting the recruitment of endogenous stem and progenitor
[326] Bioactive Decellularized Extracellular Matrix Derived from 3D Stem Cell ... — Scaffolds for tissue engineering aim to mimic the native extracellular matrix (ECM) that provides physical support and biochemical signals to modulate multiple cell behaviors. However, the majority of currently used biomaterials are oversimplified and therefore fail to provide a niche required for the stimulation of tissue regeneration.
[327] Bioactive scaffolds for tissue engineering: A review of decellularized ... — [6-9] Decellularized extracellular matrix (dECM) contains an abundance of tissue-specific growth factors and signaling molecules, which play a piv-otal role in the development of the cellular microenviron-ment niche and offer broad prospects for decellularized tissue biomaterials as natural, bioactive grafts to regulate
[328] Advances, challenges, and future directions in the clinical translation ... — The clinical translation of next generation formulations ECM scaffolds faces predictable challenges such as manufacturing, manageable regulatory pathways, surgical implantation, and the cost required to address these challenges. The current status of ECM-based biomaterials, including clinical translation, novel formulations and therapies
[330] Clinical applications of decellularized extracellular matrices for ... — In a clinical trial performed on 120 chronic leg ulcer cases, the group treated with this product demonstrated 60% of complete healing by the end of the 12 week period, compared to 35% healing in the standard treatment group. ... Lin C H et al. 2014 Evaluation of decellularized extracellular matrix of skeletal muscle for tissue engineering Int
[331] Decellularized extracellular matrix-based hydrogels for cartilage ... — Decellularized extracellular matrix (dECM) materials have emerged as promising tools in tissue engineering due to their low immunogenicity, biomimetic microenvironment, and ability to closely mimic the physicochemical properties of native tissues. ... ensuring their safety and effectiveness in clinical applications . ... Clinical trials for
[332] Research progress in decellularized extracellular matrix-derived ... — In clinical and preclinical research, biological scaffolds composed of extracellular matrix (ECM) have been used to promote the repair and reconstruction of various tissues. The clinical use of such scaffolds may be limited by the geometric and mechanical properties of the tissue or organ from which the ECM is harvested.
[333] Recent development and biomedical applications of decellularized ... — In natural tissue, the extracellular matrix is a 3D structure that contains various extracellular macromolecules, which are mainly proteins such as polysaccharides, collagen, and proteoglycans [, , ].The ECM provides physical support for cell adhesion and significantly influences cell behaviors including migration, proliferation, and differentiation.
[352] Recent development and biomedical applications of decellularized ... — With the development of technology, dECM based biomaterials have achieved tremendous success in regenerative medicine and tissue engineering .Along with that, scientists also motivated to develop a new status for the use of dECM biomaterials, for example, construct a biocompatible delivery system for the cell, drug and other therapeutic agents [1, , , ].
[353] Decellularization in Tissue Engineering and Regenerative Medicine ... — The application of dECM as wound healing products and surgical mesh devices has been reported (Damodaran and Vermette, 2018; ... Cell-derived Matrices for Tissue Engineering and Regenerative Medicine Applications. Biomater. Sci. 3 (1), 12-24. 10.1039/c4bm00246f [PMC free article] [Google Scholar]
[354] Decellularized extracellular matrix biomaterials for regenerative ... — Decellularized extracellular matrix biomaterials for regenerative therapies: Advances, challenges and clinical prospects - ScienceDirect Decellularized extracellular matrix biomaterials for regenerative therapies: Advances, challenges and clinical prospects In this review, we explore the emerging frontiers of decellularized tissue-derived and cell-derived biomaterials and bio-inks in the field of tissue engineering and regenerative medicine. This article underscores the potential of dECM biomaterials to stimulate in situ tissue repair through chemotactic effects for the development of growth factor and cell-free tissue engineering strategies. The article also identifies the challenges and opportunities in developing sterilization and preservation methods applicable for decellularized biomaterials and grafts and their translation into clinical products. For all open access content, the relevant licensing terms apply.
[355] Decellularized extracellular matrix for organoid and ... - PubMed — However, the clinical application of these techniques remained a big challenge because current commercial matrix does not represent the complexity of native microenvironment, thereby limiting the optimal regenerative capacity. Decellularized extracellular matrix (dECM) is expected to maintain key native matrix biomolecules and is believed to