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Response of zonal chondrocytes to extracellular matrix-hydrogels.

ABSTRACT: We investigated the biological response of chondrocytes isolated from different zones of articular cartilage and their cellular behaviors in poly (ethylene glycol)-based (PEG) hydrogels containing exogenous type I collagen, hyaluronic acid (HA), or chondroitin sulfate (CS). The cellular morphology was strongly dependent on the extracellular matrix component of hydrogels. Additionally, the exogenous extracellular microenvironment affected matrix production and cartilage specific gene expression of chondrocytes from different zones. CS-based hydrogels showed the strongest response in terms of gene expression and matrix accumulation for both superficial and deep zone chondrocytes, but HA and type I collagen-based hydrogels demonstrated zonal-dependent cellular responses.

SUBMITTER: Hwang NS

PROVIDER: S-EPMC2692751 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Response of zonal chondrocytes to extracellular matrix-hydrogels.

Hwang Nathaniel S NS Varghese Shyni S Lee H Janice HJ Theprungsirikul Parnduangjai P Canver Adam A Sharma Blanka B Elisseeff Jennifer J

FEBS letters 20070731 22

We investigated the biological response of chondrocytes isolated from different zones of articular cartilage and their cellular behaviors in poly (ethylene glycol)-based (PEG) hydrogels containing exogenous type I collagen, hyaluronic acid (HA), or chondroitin sulfate (CS). The cellular morphology was strongly dependent on the extracellular matrix component of hydrogels. Additionally, the exogenous extracellular microenvironment affected matrix production and cartilage specific gene expression o ...[more]

PMID: 17692846

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Hydrogels derived from central nervous system extracellular matrix.

Project description:Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair.

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Elastic, silk-cardiac extracellular matrix hydrogels exhibit time-dependent stiffening that modulates cardiac fibroblast response.

Project description:Heart failure is the leading cause of death in the United States and rapidly becoming the leading cause of death worldwide. While pharmacological treatments can reduce progression to heart failure following myocardial infarction, there still exists a need for new therapies that promote better healing postinjury for a more functional cardiac repair and methods to understand how the changes to tissue mechanical properties influence cell phenotype and function following injury. To address this need, we have optimized a silk-based hydrogel platform containing cardiac tissue-derived extracellular matrix (cECM). These silk-cECM hydrogels have tunable mechanical properties, as well as rate-controllable hydrogel stiffening over time. In vitro, silk-cECM scaffolds led to enhanced cardiac fibroblast (CF) cell growth and viability with culture time. cECM incorporation improved expression of integrin an focal adhesion proteins, suggesting that CFs were able to interact with the cECM in the hydrogel. Subcutaneous injection of silk hydrogels in rats demonstrated that addition of the cECM led to endogenous cell infiltration and promoted endothelial cell ingrowth after 4 weeks in vivo. This naturally derived silk fibroin platform is applicable to the development of more physiologically relevant constructs that replicate healthy and diseased tissue in vitro and has the potential to be used as an injectable therapeutic for cardiac repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3058-3072, 2016.

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Kidney decellularized extracellular matrix hydrogels: Rheological characterization and human glomerular endothelial cell response to encapsulation.

Project description:Hydrogels, highly-hydrated crosslinked polymer networks, closely mimic the microenvironment of native extracellular matrix (ECM) and thus present as ideal platforms for three-dimensional cell culture. Hydrogels derived from tissue- and organ-specific decellularized ECM (dECM) may retain bioactive signaling cues from the native tissue or organ that could in turn modulate cell-material interactions and response. In this study, we demonstrate that porcine kidney dECM can be processed to form hydrogels suitable for cell culture and encapsulation studies. Scanning electron micrographs of hydrogels demonstrated a fibrous ultrastructure with interconnected pores, and rheological analysis revealed rapid gelation times with shear moduli dependent upon the protein concentration of the hydrogels. Conditionally-immortalized human glomerular endothelial cells (GEnCs) cultured on top of or encapsulated within hydrogels exhibited high cell viability and proliferation over a one-week culture period. However, gene expression analysis of GEnCs encapsulated within kidney dECM hydrogels revealed significantly lower expression of several relevant genes of interest compared to those encapsulated within hydrogels composed of only purified collagen I. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2448-2462, 2018.

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Extracellular matrix hydrogels from decellularized tissues: Structure and function.

Project description:Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. STATEMENT OF SIGNIFICANCE:More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel.

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The impact of decellularization methods on extracellular matrix derived hydrogels.

Project description:Tissue-derived decellularized biomaterials are ideal for tissue engineering applications as they mimic the biochemical composition of the native tissue. These materials can be used as hydrogels for cell encapsulation and delivery. The decellularization process can alter the composition of the extracellular matrix (ECM) and thus influence the hydrogels characteristics. The aim of this study was to examine the impact of decellularization protocols in ECM-derived hydrogels obtained from porcine corneas. Porcine corneas were isolated and decellularized with SDS, Triton X-100 or by freeze-thaw cycles. All decellularization methods decreased DNA significantly when measured by PicoGreen and visually assessed by the absence of cell nuclei. Collagen and other ECM components were highly retained, as quantified by hydroxyproline content and sGAG, by histological analysis and by SDS-PAGE. Hydrogels obtained by freeze-thaw decellularization were the most transparent. The method of decellularization impacted gelation kinetics assessed by turbidimetric analysis. All hydrogels showed a fibrillary and porous structure determined by cryoSEM. Human corneal stromal cells were embedded in the hydrogels to assess cytotoxicity. SDS decellularization rendered cytotoxic hydrogels, while the other decellularization methods produced highly cytocompatible hydrogels. Freeze-thaw decellularization produced hydrogels with the overall best properties.

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Tissue extracellular matrix hydrogels as alternative to Matrigel for culturing gastrointestinal organoids

Project description:To determine the performance of the decellularized GI tissue ECM hydrogel, we analyzed differences in mRNA expression levels in native gastric tissues, gastric organoids cultured in Matrigel and those cultured in decellularized gastric ECM hydrogel. We also compared mRNA expression levels of native small intestinal tissues, small intestinal organoids grown in Matrigel and those grown in decellularized intestinal ECM hydrogel.

2022-01-30 | GSE165309 | GEO

Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics.

Project description:In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications.

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Newly synthesized extracellular matrix proteins from chondrocytes

Project description:Proteomic analysis of newly synthesized extracellular matrix secreted by chondrocytes in hydrogels.

2021-07-20 | MSV000087857 | MassIVE

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair.

Project description:Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.

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