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

Abstract

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, low mechanical stability of dECM 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 mechanical, rheological, swelling, printability and biocompatibility properties of the bioinks. 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.

Mechanobiology of the female reproductive system

“… 217 Another study developed tunable printable hydrogels composed of decellularized human heart ECM using either methacrylated gelatin (GelMA) or GelMA‐methacrylated hyaluronic acid (MeHA) hydrogels, which were dual crosslinked using UV and microbial transglutaminase, to create cardiac tissue‐like constructs. 218 By altering the concentrations of GelMA and MeHA individually and mixing them at different ratios, the Young's modulus values can be adjusted over a wide range. 218 …”

“… 218 By altering the concentrations of GelMA and MeHA individually and mixing them at different ratios, the Young's modulus values can be adjusted over a wide range. 218 …”

A Recombinant Dimethylarginine Dimethylaminohydrolase-1–Based Biotherapeutics to Pharmacologically Lower Asymmetric Dimethyl Arginine, thus Improving Postischemic Cardiac Function and Cardiomyocyte Mitochondrial Activity

“…To further examine the direct effect of ADMA lowering on cardiomyocytes, we used induced pluripotent stem cell (iPSC) derived cardiomyocytes (iCM). Our group has previously characterized human iCMs and their beating response in vitro in both 2D and 3D cardiac models (Basara et al, 2021;Ellis et al, 2021;Ozcebe et al, 2021). iCMs were subjected to hypoxia and ADMA to mimic the condition that may occur during myocardial infarction.…”

Multimaterial bioprinting and combination of processing techniques towards the fabrication of biomimetic tissues and organs

“…Several studies have reported the use of multinozzle microextrusion bioprinting for the 3D printing of soft tissues, such as the heart [30][31][32]. Lee et al developed a dual nozzle microextrusion technique enabling the high-resolution printing of collagen filaments along with cell-laden inks to engineer different components of the human heart at various scales ranging from capillaries to the full organ [30].…”