![]() Stem cells are further incorporated within this hypoxic model to unwind the role of cellular cross-talk in cancer metastasis to secondary sites such as bone. This improves the understanding of cell-ECM interaction in disease progression and therapeutic response. Porous silk sponges are able to serve as ECM support for breast and liver carcinoma, leading to development of functional solid hypoxic tumors with drug sensitivity. Structural homology with naïve disease ECM and ability to adapt different morphologies as per prerequisites of application, enhances its prospect to be explored for cancer modelling and therapy. ![]() Silk protein fibroin is structurally homologous with collagen. The most abundant cancerous ECM is collagen, playing critical role in cancer metastasis. In situ, cancer microenvironment contains extracellular matrix (ECM) and diverse cells (stem and immune cells). Thus 3D culture systems are adapted to unwind true structural and functional cancerous microenvironment. Taken together, this study showed that GelMA/Bio-IL scaffolds could be readily tailored to different tissue engineering applications particularly cardiac tissue regeneration.ĢD models are failing to predict the accuracy and efficiency of cancer therapeutics. The subcutaneous implantation of the engineered scaffolds in rats exhibited high biocompatibility and biodegradation in vivo. The in vitro 2D and 3D culture of primary rat cardiomyocytes (CMs) showed that the engineered hydrogels were highly biocompatible and could promote CM growth and function. Our results exhibited that the scaffolds possessed high conductivity in vitro and ex vivo as well as remarkable mechanical stability and strength. In this study, the electroconductive scaffolds were fabricated using two techniques: i) bulk fabrication through photopolymerization and ii) electrospinning. Bio-IL, an organic salt high water solubility and ionic conductivity, and electrochemical stability, was also used due to its biocompatibility and conductivity. GelMA, a naturally derived photocrosslinkable biopolymer, was selected due to its tunable mechanical properties, favorable biodegradation, and the presence of cell binding sites, which promote cell adhesion and proliferation. Here, we engineered highly biocompatible and conductive hydrogels for cardiac tissue regeneration by combining gelatin methacryloyl (GelMA) prepolymer and a choline-based bio-ionic liquid (Bio-IL). Tissue engineering (TE) approaches utilize different natural and synthetic materials to develop scaffolds for cardiac tissue regeneration. ![]() This issue is due to the inability of myocardium to regenerate, leaving behind a fibrous scar tissue that is unable to contract or propagate electrical impulses. Heart failure following myocardial infarction (MI) is a leading cause of death in the United States. The cardiobundle injury model is thus a realistic 3-D system to test new small molecule and gene therapies targeting CM regeneration in the terminally differentiated heart, with higher throughput than in vivo studies on the intact heart.Īcknowledgments: NIH grant HL134764, Foundation Leducq grant, NSF GRF # 2013126035. Electrical stimulation of injured cardiobundles results in partial yet incomplete regeneration and recovery of contractile force. Furthermore, we establish various injury methods (e.g., cardiotoxin, hydrogen peroxide, calcium ionophores) that result in CM death and a 60-80% decline in the cardiobundles' active contractile force, enabling studies of CM regeneration and functional recovery after cardiac injury. Here, we show that CM in cardiobundles stop proliferating (<1% turnover per day) after 2 weeks in standard culture conditions, representing a high-fidelity in vitro model to test potential therapies for re-activation of the cell cycle in post-mitotic myocardium. We have previously engineered 3-dimensional cylindrical tissues (“cardiobundles”) made from neonatal rat CM embedded in fibrin-based hydrogel (∼16 cardiobundles derived from 1 neonatal heart), which accurately mimic the dense and anisotropic cellular structure of native myocardium while also displaying tissue-level functional properties comparable to the adult or adolescent heart. Thus, therapies to induce endogenous regeneration of the heart would significantly improve cardiac function in the setting of heart disease. Cardiomyocytes (CM) in the adult mammalian heart have limited capacity to proliferate following injury.
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