Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Abstract

Bioprinting holds great promise toward engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, a novel and mechanically robust biomaterial‐ink based on nonmulberry silk fibroin protein is developed. The silk‐based ink demonstrates suitable mechanical properties required in terms of elasticity and stiffness (≈40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allows the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which are able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin‐43, and maintain synchronously beating of cardiomyocytes. The printed constructs are found to be nonimmunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue‐on‐a‐chip, the silk‐based ink is used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC‐CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. The ability is confirmed of silk‐based supporting hydrogel toward maturation and viability of hiPSC‐CSs and endothelial cells, and for applications in evaluating drug toxicity.

Light‐Controlled Growth Factors Release on Tetrapodal ZnO‐Incorporated 3D‐Printed Hydrogels for Developing Smart Wound Scaffold

“…1 cm diameter samples with 600 µm thickness with different concentrations of t‐ZnO and VEGF coated t‐ZnO were prepared by using the previously described protocol. [ 51 ] Hydrogel samples were stored in 1.5 mL centrifuge tubes and frozen during 24 h at −20 °C. After this procedure, the samples underwent lyophilization for 24 h, and several transversal cuts were performed in different sections of the hydrogels.…”

3D Printing Techniques and Their Applications to Organ-on-a-Chip Platforms: A Systematic Review

“…Recently, Mehrotra et al [ 51 ] developed an innovative biomaterial-ink based on non-mulberry silk fibroin (nSF) protein. n-SF protein is mechanically robust and can be utilized as an ink component in order to improve the mechanical strength of inks, while maintaining their unique physical and biological properties.…”

“…Despite the outstanding properties of gelatin-based hydrogels, bioinks composed of other biomaterials have been proposed, as silk-based ink [ 51 ]. This new ink showed excellent properties for developing viable cardiac muscle tissues in vitro, while maintaining its functionality.…”

“…Although gelatin-based hydrogels are the most commonly used, other formulations should be developed, for instance, by creating composite bioinks, combining the advantages of different materials, or making some modifications of the existing ones. An important finding in this field was presented by Mehrotra et al [ 51 ], in which a non-mulberry silk fibroin was developed for engineering myocardial tissues.…”

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery

“…Some of these immature properties have been proven to be difficult to overcome, such as the development of t-tubules and abolition of immature spontaneous membrane potential oscillation (Lundy et al, 2013;Keung et al, 2014;Karakikes et al, 2015). Despite the existence of these immature traits, we and others have utilized hiPSC/hESC derived cardiomyocytes to study the effects of doxorubicin and were able to demonstrate its cardiotoxic effects in vitro (Sirenko et al, 2013;Holmgren et al, 2015;Burridge et al, 2016;Cheung et al, 2020) as well as assess and predict cardiotoxicity in patients (Cheung et al, 2020) by measuring a number of parameters that can directly or indirectly assess the functionality and viability of hiPSC-CMs, including cell viability, contractility, single cell electrophysiology and calcium transients, as well as the detection of biomarkers such as cardiac troponins, micro-RNAs (Cheung et al, 2020;Mehrotra et al, 2020), creatine kinase (Shin et al, 2016) etc, often in high content fashion and longitudinal measurements. Burridge et al demonstrated that patient-specific hiPSC-CMs can recapitulate predilection of breast cancer patients to AIC at the single cell level (Burridge et al, 2016).…”