Cardiovascular human organ-on-a-chip platform for disease modeling, drug development, and personalized therapy.

Cardiovascular organ-on-a-chip (OoC) devices are composed of engineered or native functional tissues that are cultured under controlled microenvironments inside microchips. These systems employ microfabrication and tissue engineering techniques to recapitulate human physiology. This review focuses on human OoC systems to model cardiovascular diseases, to perform drug screening, and to advance personalized medicine. We also address the challenges in the generation of organ chips that can revolutionize the large-scale application of these systems for drug development and personalized therapy.

Engineering Spatiotemporal Control in Vascularized Tissues.

A major challenge in engineering scalable three-dimensional tissues is the generation of a functional and developed microvascular network for adequate perfusion of oxygen and growth factors. Current biological approaches to creating vascularized tissues include the use of vascular cells, soluble factors, and instructive biomaterials. Angiogenesis and the subsequent generation of a functional vascular bed within engineered tissues has gained attention and is actively being studied through combinations of physical and chemical signals, specifically through the presentation of topographical growth factor signals. The spatiotemporal control of angiogenic signals can generate vascular networks in large and dense engineered tissues. This review highlights the developments and studies in the spatiotemporal control of these biological approaches through the coordinated orchestration of angiogenic factors, differentiation of vascular cells, and microfabrication of complex vascular networks. Fabrication strategies to achieve spatiotemporal control of vascularization involves the incorporation or encapsulation of growth factors, topographical engineering approaches, and 3D bioprinting techniques. In this article, we highlight the vascularization of engineered tissues, with a focus on vascularized cardiac patches that are clinically scalable for myocardial repair. Finally, we discuss the present challenges for successful clinical translation of engineered tissues and biomaterials.

Advances in three-dimensional bioprinted stem cell-based tissue engineering for cardiovascular regeneration.

Three-dimensional (3D) bioprinting of cellular or biological components are an emerging field to develop tissue structures that mimic the spatial, mechanochemical and temporal characteristics of cardiovascular tissues. 3D multi-cellular and multi-domain organotypic biological constructs can better recapitulate in vivo physiology and can be utilized in a variety of applications. Such applications include in vitro cellular studies, high-throughput drug screening, disease modeling, biocompatibility analysis, drug testing and regenerative medicine. A major challenge of 3D bioprinting strategies is the inability of matrix molecules to reconstitute the complexity of the extracellular matrix and the intrinsic cellular morphologies and functions. An important factor is the inclusion of a vascular network to facilitate oxygen and nutrient perfusion in scalable and patterned 3D bioprinted tissues to promote cell viability and functionality. In this review, we summarize the new generation of 3D bioprinting techniques, the kinds of bioinks and printing materials employed for 3D bioprinting, along with the current state-of-the-art in engineered cardiovascular tissue models. We also highlight the translational applications of 3D bioprinting in engineering the myocardium cardiac valves, and vascular grafts. Finally, we discuss current challenges and perspectives of designing effective 3D bioprinted constructs with native vasculature, architecture and functionality for clinical translation and cardiovascular regeneration.

Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering.

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs. In this review, we summarize the in vitro, pre-clinical, and clinical research models that have been employed in the design of ECM-based biomaterials for cardiovascular regenerative medicine. We highlight the research advancements in the incorporation of ECM components into biomaterial-based scaffolds, the engineering of increasingly complex structures using biofabrication and spatial patterning techniques, the regulation of ECMs on vascular differentiation and function, and the translation of ECM-based scaffolds for vascular graft applications. Finally, we discuss the challenges, future perspectives, and directions in the design of next-generation ECM-based biomaterials for cardiovascular tissue engineering and clinical translation.

Surface modification of polypropylene surgical meshes for improving adhesion with poloxamine hydrogel adhesive.

Tissue adhesive has notable clinical benefits in hernia repair fixation. A novel poloxamine tissue adhesive was previously shown to successfully bond collagen tissue with adequate adhesive strength. In application related to attachment of polypropylene (PP) mesh, the adhesive strength between the mesh and poloxamine hydrogel adhesive is limited by the hydrophobicity of PP monofilaments and lack of covalent bond formation. The purpose of this study was to compare two different surface modifications [bovine serum albumin (BSA) adsorption and poly-glycidyl methacrylate/human serum albumin (PGMA/HSA) grafting] of PP mesh for improving the adhesive strength between poloxamine hydrogel adhesive and PP mesh. The PGMA/HSA surface modification significantly improved the adhesive strength for meshes attached with poloxamine hydrogel tissue adhesive compared with unmodified meshes and meshes modified by BSA adsorption. An area of 1 cm2 adhesive provided for a maximum adhesive strength of 65-70 kPa for meshes modified by PGMA/HSA, 4-13 kPa for meshes modified by BSA, and 22-45 kPa for unmodified meshes. Optical microscopy and infrared spectroscopy (FTIR) confirmed the improved adhesive strength was achieved through mechanical interlock of the hydrogel tissue adhesive into the PP mesh pores and chemical bonding of the albumin after successful PGMA/HSA grafting onto the PP monofilaments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1047-1055, 2019.