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Bioengineered tissues have become increasingly more sophisticated owing to recent advancements in the fields of biomaterials, microfabrication, microfluidics, genetic engineering, and stem cell and developmental biology. In the coming years, the ability to engineer artificial constructs that accurately mimic the compositional, architectural, and functional properties of human tissues, will profoundly impact the therapeutic and diagnostic aspects of the healthcare industry. In this regard, bioengineered cardiac tissues are of particular importance due to the extremely limited ability of the myocardium to self-regenerate, as well as the remarkably high mortality associated with cardiovascular diseases worldwide. As novel microphysiological systems make the transition from bench to bedside, their implementation in high throughput drug screening, personalized diagnostics, disease modeling, and targeted therapy validation will bring forth a paradigm shift in the clinical management of cardiovascular diseases. Here, we will review the current state of the art in experimental in vitro platforms for next generation diagnostics and therapy validation. We will describe recent advancements in the development of smart biomaterials, biofabrication techniques, and stem cell engineering, aimed at recapitulating cardiovascular function at the tissue- and organ levels. In addition, integrative and multidisciplinary approaches to engineer biomimetic cardiovascular constructs with unprecedented human and clinical relevance will be discussed. We will comment on the implementation of these platforms in high throughput drug screening, in vitro disease modeling and therapy validation. Lastly, future perspectives will be provided on how these biomimetic platforms will aid in the transition towards patient centered diagnostics, and the development of personalized targeted therapeutics.

Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

The design of new hydrogel-based biomaterials with tunable physical and biological properties is essential for the advancement of applications related to tissue engineering and regenerative medicine. For instance, interpenetrating polymer network (IPN) and semi-IPN hydrogels have been widely explored to engineer functional tissues due to their characteristic microstructural and mechanical properties. Here, we engineered IPN and semi-IPN hydrogels comprised of a tough pectin grafted polycaprolactone (pectin-g-PCL) component to provide mechanical stability, and a highly cytocompatible gelatin methacryloyl (GelMA) component to support cellular growth and proliferation. IPN hydrogels were formed by calcium ion (Ca2+)-crosslinking of pectin-g-PCL chains, followed by photocrosslinking of the GelMA precursor. Conversely, semi-IPN networks were formed by photocrosslinking of the pectin-g-PCL and GelMA mixture, in the absence of Ca2+ crosslinking. IPN and semi-IPN hydrogels synthesized with varying ratios of pectin-g-PCL to GelMA, with and without Ca2+-crosslinking, exhibited a broad range of mechanical properties. For semi-IPN hydrogels, the aggregation of microcrystalline cores led to formation of hydrogels with compressive moduli ranging from 3.1 to 10.4 kPa. For IPN hydrogels, the mechanistic optimization of pectin-g-PCL, GelMA, and Ca2+ concentrations resulted in hydrogels with comparatively higher compressive modulus, in the range of 39 kPa-5029 kPa. Our results also showed that IPN hydrogels were cytocompatible in vitro and could support the growth of three-dimensionally (3D) encapsulated MC3T3-E1 preosteoblasts in vitro. The simplicity, technical feasibility, low cost, tunable mechanical properties, and cytocompatibility of the engineered semi-IPN and IPN hydrogels highlight their potential for different tissue engineering and biomedical applications.

Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5-56 kPa by changing the concentrations of the initiator, co-initiator and co-monomer in the precursor formulation. In addition, the average pore sizes (26-103 μm) and swelling ratios (7-13%) were also shown to be tunable by varying the hydrogel formulation. In vitro studies showed that visible light crosslinked GelMA hydrogels supported the growth and function of primary cardiomyocytes (CMs). In addition, the engineered materials were shown to be biocompatible in vivo, and could be successfully delivered to the heart after myocardial infarction in an animal model to promote tissue healing. The developed visible light crosslinked hydrogel could be used for the repair of various soft tissues such as the myocardium and for the treatment of cardiovascular diseases with enhanced therapeutic functionality.

Conventional methods to engineer electroconductive hydrogels (ECHs) through the incorporation of conductive nanomaterials and polymers exhibit major technical limitations. These are mainly associated with the cytotoxicity, as well as poor solubility, processability, and biodegradability of their components. Here, we describe the engineering of a new class of ECHs through the functionalization of non-conductive polymers with a conductive choline-based bio-ionic liquid (Bio-IL). Bio-IL conjugated hydrogels exhibited a wide range of highly tunable physical properties, remarkable in vitro and in vivo biocompatibility, and high electrical conductivity without the need for additional conductive components. The engineered hydrogels could support the growth and function of primary cardiomyocytes in both two dimentinal (2D) and three dimensional (3D) cultures in vitro. Furthermore, they were shown to be efficiently biodegraded and possess low immunogenicity when implanted subcutaneously in rats. Taken together, our results suggest that Bio-IL conjugated hydrogels could be implemented and readily tailored to different biomedical and tissue engineering applications.