Biodegradable, Biocompatible, and Implantable Multifunctional Sensing Platform for Cardiac Monitoring.

Cardiac monitoring after heart surgeries is crucial for health maintenance and detecting postoperative complications early. However, current methods like rigid implants have limitations, as they require performing second complex surgeries for removal, increasing infection and inflammation risks, thus prompting research for improved sensing monitoring technologies. Herein, we introduce a nanosensor platform that is biodegradable, biocompatible, and integrated with multifunctions, suitable for use as implants for cardiac monitoring. The device has two electrochemical biosensors for sensing lactic acid and pH as well as a pressure sensor and a chemiresistor array for detecting volatile organic compounds. Its biocompatibility with myocytes has been tested in vitro, and its biodegradability and sensing function have been proven with ex vivo experiments using a three-dimensional (3D)-printed heart model and 3D-printed cardiac tissue patches. Moreover, an artificial intelligence-based predictive model was designed to fuse sensor data for more precise health assessment, making it a suitable candidate for clinical use. This sensing platform promises impactful applications in the realm of cardiac patient care, laying the foundation for advanced life-saving developments.

Post-Maturation Reinforcement of 3D-Printed Vascularized Cardiac Tissues.

Despite advances in biomaterials engineering, a large gap remains between the weak mechanical properties that can be achieved with natural materials and the strength of synthetic materials. Here, a method is presented for reinforcing an engineered cardiac tissue fabricated from differentiated induced pluripotent stem cells (iPSCs) and an extracellular matrix (ECM)-based hydrogel in a manner that is fully biocompatible. The reinforcement occurs as a post-fabrication step, which allows for the use of 3D-printing technology to generate thick, fully cellularized, and vascularized cardiac tissues. After tissue assembly and during the maturation process in a soft hydrogel, a small, tissue-penetrating reinforcer is deployed, leading to a significant increase in the tissue's mechanical properties. The tissue's robustness is demonstrated by injecting the tissue in a simulated minimally invasive procedure and showing that the tissue is functional and undamaged at the nano-, micro-, and macroscales.

Imageable AuNP-ECM Hydrogel Tissue Implants for Regenerative Medicine.

In myocardial infarction, a blockage in one of the coronary arteries leads to ischemic conditions in the left ventricle of the myocardium and, therefore, to significant death of contractile cardiac cells. This process leads to the formation of scar tissue, which reduces heart functionality. Cardiac tissue engineering is an interdisciplinary technology that treats the injured myocardium and improves its functionality. However, in many cases, mainly when employing injectable hydrogels, the treatment may be partial because it does not fully cover the diseased area and, therefore, may not be effective and even cause conduction disorders. Here, we report a hybrid nanocomposite material composed of gold nanoparticles and an extracellular matrix-based hydrogel. Such a hybrid hydrogel could support cardiac cell growth and promote cardiac tissue assembly. After injection of the hybrid material into the diseased area of the heart, it could be efficiently imaged by magnetic resonance imaging (MRI). Furthermore, as the scar tissue could also be detected by MRI, a distinction between the diseased area and the treatment could be made, providing information about the ability of the hydrogel to cover the scar. We envision that such a nanocomposite hydrogel may improve the accuracy of tissue engineering treatment.

Bioengineering approaches to treat the failing heart: from cell biology to 3D printing.

Successfully engineering a functional, human, myocardial pump would represent a therapeutic alternative for the millions of patients with end-stage heart disease and provide an alternative to animal-based preclinical models. Although the field of cardiac tissue engineering has made tremendous advances, major challenges remain, which, if properly resolved, might allow the clinical implementation of engineered, functional, complex 3D structures in the future. In this Review, we provide an overview of state-of-the-art studies, challenges that have not yet been overcome and perspectives on cardiac tissue engineering. We begin with the most clinically relevant cell sources used in this field and discuss the use of topological, biophysical and metabolic stimuli to obtain mature phenotypes of cardiomyocytes, particularly in relation to organized cytoskeletal and contractile intracellular structures. We then move from the cellular level to engineering planar cardiac patches and discuss the need for proper vascularization and the main strategies for obtaining it. Finally, we provide an overview of several different approaches for the engineering of volumetric organs and organ parts - from whole-heart decellularization and recellularization to advanced 3D printing technologies.

Drug-Eluting Rubber Bands for Tissue Ligation.

Rubber band ligation is a commonly used method for the removal of tissue abnormalities. Most often, rubber band ligation is performed to remove internal hemorrhoids unresponsive to first line treatments to avoid surgery. While the procedure is considered safe, patients experience mild to significant pain and discomfort until the tissue sloughs off. As patients often require multiple bandings and sessions, reducing these side effects can have a considerable effect on patient adherence and quality of life. To reduce pain and discomfort, we developed drug-eluting rubber bands for ligation procedures. We investigated the potential for a band to elute anesthetics and drug combinations to durably manage pain for a period of up to 5 days while exhibiting similar mechanical properties to conventional rubber bands. We show that the rubber bands retain their mechanical properties despite significant drug loading. Lidocaine, released from the bands, successfully altered the calcium dynamics of cardiomyocytes in vitro and modulated heart rate in zebrafish embryos, while the bands exhibited lower cytotoxicity than conventional bands. Ex vivo studies demonstrated substantial local drug release in enteric tissues. These latex-free bands exhibited sufficient mechanical and drug-eluting properties to serve both ligation and local analgesic functions, potentially enabling pain reduction for multiple indications.

Injectable Nanocomposite Implants Reduce ROS Accumulation and Improve Heart Function after Infarction.

In a myocardial infarction, blood supply to the left ventricle is abrogated due to blockage of one of the coronary arteries, leading to ischemia, which further triggers the generation of reactive oxygen species (ROS). These sequential processes eventually lead to the death of contractile cells and affect the integrity of blood vessels, resulting in the formation of scar tissue. A new heart therapy comprised of cardiac implants encapsulated within an injectable extracellular matrix-gold nanoparticle composite hydrogel is reported. The particles on the collagenous fibers within the hydrogel promote fast transfer of electrical signal between cardiac cells, leading to the functional assembly of the cardiac implants. The composite hydrogel is shown to absorb reactive oxygen species in vitro and in vivo in mice ischemia reperfusion model. The reduction in ROS levels preserve cardiac tissue morphology and blood vessel integrity, reduce the scar size and the inflammatory response, and significantly prevent the deterioration of heart function.

Nanoengineered Peptide-Based Antimicrobial Conductive Supramolecular Biomaterial for Cardiac Tissue Engineering.

Owing to their dynamic nature and ordered architecture, supramolecular materials strikingly resemble organic components of living systems. Although short-peptide self-assembled nanostructured hydrogels are regarded as intriguing supramolecular materials for biotechnology, their application is often limited due to their low stability and considerable challenge of combining other desirable properties. Herein, a di-Fmoc-based hydrogelator containing the cell-adhesive Arg-Gly-Asp (RGD) fragment that forms a mechanically stable, self-healing hydrogel is designed. Molecular dynamics simulation reveals the presence of RGD segments on the surface of the hydrogel fibers, highlighting their cell adherence capacity. Aiming to impart conductivity, the 3D network of the hydrogel is further nanoengineered by incorporating polyaniline (PAni). The composite hydrogels demonstrate semiconductivity, excellent antibacterial activity, and DNA binding capacity. Cardiac cells grown on the surface of the composite hydrogels form functional synchronized monolayers. Taken together, the combination of these attributes in a single hydrogel suggests it as an exceptional candidate for functional supramolecular biomaterial designed for electrogenic tissue engineering.

Transparent support media for high resolution 3D printing of volumetric cell-containing ECM structures.

3D bioprinting may revolutionize the field of tissue engineering by allowing fabrication of bio-structures with a high degree of complexity, fine architecture and heterogeneous composition. The printing substances in these processes are mostly based on biomaterials and living cells. As such, they generally possess weak mechanical properties and thus must be supported during fabrication in order to prevent the collapse of large, volumetric multi-layered printouts. In this work, we characterize a uniquely formulated media used to support printing of extracellular matrix-based biomaterials. We show that a hybrid material, comprised of calcium-alginate nanoparticles and xanthan gum, presents superb qualities that enable printing at high resolution of down to 10 microns, allowing fabrication of complex constructs and cellular structures. This hybrid also presents an exclusive combination of desirable properties such as biocompatibility, high transparency, stability at a wide range of temperatures and amenability to delicate extraction procedures. Moreover, as fabrication of large, volumetric biological structures may require hours and even days to accomplish, we have demonstrated that the hybrid medium can support prolonged, precise printing for at least 18 h. All these qualities make it a promising support medium for 3D printing of tissues and organs.