Abstract
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.
Highlights
Vascular diseases such as atherosclerosis, aortic aneurysm, and peripheral arterial disease are a major cause of mortality and loss of quality of life [1]
Besides the extracellular matrix (ECM) found in the basement membrane, the ECMs found in other parts of blood vessels include elastin that provides elasticity and collagen for structural integrity
We previously demonstrated using arrayed ECM microenvironments that human induced pluripotent stem cell-derived endothelial cells (ECs) cultured on multi-component
Summary
Vascular diseases such as atherosclerosis, aortic aneurysm, and peripheral arterial disease are a major cause of mortality and loss of quality of life [1]. The ECM plays a vital role in vascular tissue engineering by providing both a physical scaffold for structural integrity and 3D shape, as well as relaying intrinsic biochemical and mechanical cues that regulate cellular function. There has been tremendous progress in the field of vascular tissue engineering and regenerative medicine in the past decades, notably with the development of biomaterials derived from ECM proteins that provide mechanical support and biochemical signals that modulate vascular cell attachment, phenotype, and behavior. ECM-derived biomaterials were initially used as two-dimensional (2D) coatings for the improved cell adhesion to tissue culture polystyrene dishes. We highlight major developments in biomaterials derived from mammalian ECM in the field of vascular tissue engineering and regenerative medicine, with a focus on translational applications. We discuss the efficacy of ECM-derived biomaterials to regenerate and repair tissues, along with the progression of therapies from in vitro to preclinical studies, and towards clinical translation
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