Cardiac tissue-derived extracellular matrix scaffolds for myocardial repair: advantages and challenges

AbstractDecellularized extracellular matrix (dECM) derived from myocardium has been widely explored as a nature scaffold for cardiac tissue engineering applications. Cardiac dECM offers many unique advantages such as preservation of organ-specific ECM microstructure and composition, demonstration of tissue-mimetic mechanical properties and retention of biochemical cues in favor of subsequent recellularization. However, current processes of dECM decellularization and recellularization still face many challenges including the need for balance between cell removal and extracellular matrix preservation, efficient recellularization of dECM for obtaining homogenous cell distribution, tailoring material properties of dECM for enhancing bioactivity and prevascularization of thick dECM. This review summarizes the recent progresses of using dECM scaffold for cardiac repair and discusses its major advantages and challenges for producing biomimetic cardiac patch.

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Tunable Human Myocardium Derived Decellularized Extracellular Matrix for 3D Bioprinting and Cardiac Tissue Engineering

Gels ◽

10.3390/gels7020070 ◽

2021 ◽

Vol 7 (2) ◽

pp. 70

Author(s):

Gozde Basara ◽

S. Gulberk Ozcebe ◽

Bradley W. Ellis ◽

Pinar Zorlutuna

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Extracellular Matrix ◽

Connexin 43 ◽

Cardiac Tissue ◽

Myocardial Infarct ◽

Cardiac Tissue Engineering ◽

3D Bioprinting ◽

Decellularized Extracellular Matrix ◽

Order Of Magnitude

The generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA-methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability, and biocompatibility properties. Composite GelMA–MeHA–dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude compared to the GelMA–dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cell derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modeling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over the mechanical properties along with the cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.

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Tunable human myocardium derived decellularized extracellular matrix for 3D bioprinting and cardiac tissue engineering

10.1101/2021.03.30.437600 ◽

2021 ◽

Author(s):

Gozde Basara ◽

S. Gulberk Ozcebe ◽

Bradley W. Ellis ◽

Pinar Zorlutuna

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Extracellular Matrix ◽

Connexin 43 ◽

Cardiac Tissue ◽

Myocardial Infarct ◽

Cardiac Tissue Engineering ◽

3D Bioprinting ◽

Decellularized Extracellular Matrix ◽

Order Of Magnitude

AbstractThe generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA- methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial Transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability and biocompatibility properties. Composite GelMA-MeHA-dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude, compared to GelMA-dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cells derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and Connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modelling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over mechanical properties along with cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.

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Mechanical properties of decellularized extracellular matrix coated with TiCaPCON film

Biomedical Materials ◽

10.1088/1748-605x/aa6fc0 ◽

2017 ◽

Vol 12 (3) ◽

pp. 035014 ◽

Cited By ~ 8

Author(s):

I V Sukhorukova ◽

A N Sheveyko ◽

K L Firestein ◽

Ph V Kiryukhantsev-Korneev ◽

D Golberg ◽

...

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Decellularized Extracellular Matrix

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Reinforcement of a decellularized extracellular matrix-derived hydrogel using nanofibers for cardiac tissue engineering

International Journal of Advanced Biological and Biomedical Research ◽

10.33945/sami/ijabbr.2020.3.8 ◽

2020 ◽

Vol 8 (3) ◽

pp. 302-313

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Cardiac Tissue ◽

Cardiac Tissue Engineering ◽

Decellularized Extracellular Matrix

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Abstract 396: 3d-Engineered Aligned Co-axial Nanofibrous Cardiac Patch for Drug Screening and Cardiac Repair Applications

Circulation Research ◽

10.1161/res.127.suppl_1.396 ◽

2020 ◽

Vol 127 (Suppl_1) ◽

Author(s):

Mahmood Khan ◽

Divya Sridharan ◽

Naresh Kumar ◽

Arunumar Palaniappan ◽

Julie A Dougherty ◽

...

Keyword(s):

Drug Screening ◽

Connexin 43 ◽

Cardiac Tissue ◽

Cardiac Repair ◽

Confocal Imaging ◽

Test Machine ◽

Similar Response ◽

Calcium Cycling ◽

Tissue Model ◽

Cardiac Patch

Introduction: Recent studies have demonstrated the great potential of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for testing the efficacy of various cardiac drugs. Additionally, studies have shown that the hiPSC-CMs grown in a 3D environment express better physiological characteristics than 2D cultures. The convergence of polymeric cardiac patch technology with hiPSC-CMs has opened up innovative ways for generating biomimetic 3D cardiac tissues. Hypothesis: The central hypothesis of this study was to develop a 3D cardiac tissue model for pharmacological testing of various cardiac drugs on a 3D nanofibrous aligned co-axial cardiac patch. Methods: A co-axial (Co-A) PCL-gelatin aligned nanofibrous patch was fabricated using the electrospinning technique and its mechanical properties were assessed using Universal Test Machine. Then, the hiPSC-CMs were cultured on this Co-A patch for 2 weeks and the LDH assay was performed to determine the cell viability. The functionality of the cardiac patch was determined by an assessment of calcium cycling in hiPSC-CMs. Further, particle image velocimetry (PIV) and microelectrode array (MEA) was used to evaluate the physiological functionality of the cardiac patch in response to various cardiac drugs. Results: Our studies showed that the mean diameter and thickness of aligned Co-A nanofibrous patch was 578±184 nm and 115±11 μm respectively, while its tensile strength was 0.780 ± 0.098 MPa. Further, confocal imaging confirmed the core-shell structure of the Co-A patches with a core diameter of 2.21 ± 0.50 μm. Additionally, The hiPSC-CMs cultured on these aligned Co-A patches showed an aligned morphology and expressed Troponin-T, GATA4, α-sarcomeric actinin, and connexin-43. The hiPSC-CMs seeded on a 3D scaffold showed efficient calcium cycling properties, which were similar to the hiPSC-CMs cultured in 2D scaffold. Furthermore, PIV and MEA analysis showed that hiPSC-CMs cultured in 2D and 3D showed a similar response to various cardiac drugs, isoproterenol, verapamil and E4031. Conclusions: Overall, this study demonstrated a successful fabrication of aligned Co-A nanofibrous cardiac patch and its evaluation as a 3D cardiac tissue model in-vitro, which could be applied towards drug screening, toxicity studies and cardiac repair applications for ischemic heart disease.

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Digital image correlation-based point-wise inverse characterization of heterogeneous material properties of gallbladder in vitro

Proceedings of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rspa.2014.0152 ◽

2014 ◽

Vol 470 (2167) ◽

pp. 20140152 ◽

Cited By ~ 24

Author(s):

Katia Genovese ◽

Luciana Casaletto ◽

Jay D. Humphrey ◽

Jia Lu

Keyword(s):

Mechanical Properties ◽

Extracellular Matrix ◽

Material Properties ◽

Soft Tissues ◽

Applied Pressure ◽

Heterogeneous Material ◽

Image Correlation ◽

Surface Geometry ◽

Stress Strain ◽

Full Field

Continuing advances in mechanobiology reveal more and more that many cell types, especially those responsible for establishing, maintaining, remodelling or repairing extracellular matrix, are extremely sensitive to their local mechanical environment. Indeed, it appears that they fashion the extracellular matrix so as to promote a ‘mechanical homeostasis’. A natural corollary, therefore, is that cells will try to offset complexities in geometry and applied loads with heterogeneous material properties in order to render their local environment mechanobiologically favourable. There is a pressing need, therefore, for hybrid experimental–computational methods in biomechanics that can quantify such heterogeneities. In this paper, we present an approach that combines experimental information on full-field surface geometry and deformations with a membrane-based point-wise inverse method to infer full-field mechanical properties for soft tissues that exhibit nonlinear behaviours under finite deformations. To illustrate the potential utility of this new approach, we present the first quantification of regional mechanical properties of an excised but intact gallbladder, a thin-walled, sac-like organ that plays a fundamental role in normal digestion. The gallbladder was inflated to a maximum local stretch of 120% in eight pressure increments; at each pressure pause, the entire three-dimensional surface was optically extracted, and from which the surface strains were computed. Wall stresses in each state were predicted from the deformed geometry and the applied pressure using an inverse elastostatic method. The elastic properties of the gallbladder tissue were then characterized locally using point-wise stress–strain data. The gallbladder was found to be highly heterogeneous, with drastically different stiffness between the hepatic and the serosal sides. The identified material model was validated through forward finite-element analysis; both the configurations and the local stress–strain patterns were well reproduced.

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