skip to main content

Title: 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.  more » « less
Award ID(s):
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Journal of Cardiovascular Development and Disease
Page Range / eLocation ID:
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Cardiovascular diseases, including myocardial infarction (MI), persist as the leading cause of mortality and morbidity worldwide. The limited regenerative capacity of the myocardium presents significant challenges specifically for the treatment of MI and, subsequently, heart failure (HF). Traditional therapeutic approaches mainly rely on limiting the induced damage or the stress on the remaining viable myocardium through pharmacological regulation of remodeling mechanisms, rather than replacement or regeneration of the injured tissue. The emerging alternative regenerative medicine-based approaches have focused on restoring the damaged myocardial tissue with newly engineered functional and bioinspired tissue units. Cardiac regenerative medicine approaches can be broadly categorized into three groups: cell-based therapies, scaffold-based cardiac tissue engineering, and scaffold-free cardiac tissue engineering. Despite significant advancements, however, the clinical translation of these approaches has been critically hindered by two key obstacles for successful structural and functional replacement of the damaged myocardium, namely: poor engraftment of engineered tissue into the damaged cardiac muscle and weak electromechanical coupling of transplanted cells with the native tissue. To that end, the integration of micro- and nanoscale technologies along with recent advancements in stem cell technologies have opened new avenues for engineering of structurally mature and highly functional scaffold-based (SB-CMTs) and scaffold-free cardiac microtissues (SF-CMTs) with enhanced cellular organization and electromechanical coupling for the treatment of MI and HF. In this review article, we will present the state-of-the-art approaches and recent advancements in the engineering of SF-CMTs for myocardial repair. 
    more » « less
  2. Abstract

    Tissue engineered grafts show great potential as regenerative implants for diseased or injured tissues within the human body. However, these grafts suffer from poor nutrient perfusion and waste transport, thus decreasing their viability post‐transplantation. Graft vascularization is therefore a major area of focus within tissue engineering because biologically relevant conduits for nutrient and oxygen perfusion can improve viability post‐implantation. Many researchers used microphysiological systems as testing platforms for potential grafts owing to an ability to integrate vascular networks as well as biological characteristics such as fluid perfusion, 3D architecture, compartmentalization of tissue‐specific materials, and biophysical and biochemical cues. Although many methods of vascularizing these systems exist, microvascular self‐assembly has great potential for bench‐to‐clinic translation as it relies on naturally occurring physiological events. In this review, the past decade of literature is highlighted, and the most important and tunable components yielding a self‐assembled vascular network on chip are critically discussed: endothelial cell source, tissue‐specific supporting cells, biomaterial scaffolds, biochemical cues, and biophysical forces. This paper discusses the bioengineered systems of angiogenesis, vasculogenesis, and lymphangiogenesis and includes a brief overview of multicellular systems. It concludes with future avenues of research to guide the next generation of vascularized microfluidic models.

    more » « less
  3. Abstract

    Mechanically flexible and conformable materials and integrated devices have found diverse applications in personalized healthcare as diagnostics and therapeutics, tissue engineering and regenerative medicine constructs, surgical tools, secure systems, and assistive technologies. In order to impart optimal mechanical properties to the (bio)materials used in these applications, various strategies have been explored—from composites to structural engineering. In recent years, geometric cuts inspired by the art of paper‐cutting, referred to as kirigami, have provided innovative opportunities for conferring precise mechanical properties via material removal. Kirigami‐based approaches have been used for device design in areas ranging from soft bioelectronics to energy storage. In this review, the principles of kirigami‐inspired engineering specifically for biomedical applications are discussed. Factors pertinent to their design, including cut geometry, materials, and fabrication, and the effect these parameters have on their properties and configurations are covered. Examples of kirigami designs in healthcare are presented, such as, various form factors of sensors (on skin, wearable), implantable devices, therapeutics, surgical procedures, and cellular scaffolds for regenerative medicine. Finally, the challenges and future scope for the successful translation of these biodesign concepts to broader deployment are discussed.

    more » « less
  4. Load-bearing soft tissues normally show J-shaped stress–strain behaviors with high compliance at low strains yet high strength at high strains. They have high water content but are still tough and durable. By contrast, naturally derived hydrogels are weak and brittle. Although hydrogels prepared from synthetic polymers can be strong and tough, they do not have the desired bioactivity for emerging biomedical applications. Here, we present a thermomechanical approach to replicate the combinational properties of soft tissues in protein-based photocrosslinkable hydrogels. As a demonstration, we create a gelatin methacryloyl fiber hydrogel with soft tissue-like mechanical properties, such as low Young’s modulus (0.1 to 0.3 MPa), high strength (1.1 ± 0.2 MPa), high toughness (9,100 ± 2,200 J/m 3 ), and high fatigue resistance (2,300 ± 500 J/m 2 ). This hydrogel also resembles the biochemical and architectural properties of native extracellular matrix, which enables a fast formation of 3D interconnected cell meshwork inside hydrogels. The fiber architecture also regulates cellular mechanoresponse and supports cell remodeling inside hydrogels. The integration of tissue-like mechanical properties and bioactivity is highly desirable for the next-generation biomaterials and could advance emerging fields such as tissue engineering and regenerative medicine. 
    more » « less
  5. Abstract

    Stem cells have been sought as a promising cell source in the tissue engineering field due to their proliferative capacity as well as differentiation potential. Biomaterials have been utilized to facilitate the delivery of stem cells in order to improve their engraftment and long‐term viability upon implantation. Biomaterials also have been developed as scaffolds to promote stem cell induced tissue regeneration. This review focuses on the latter where the biomaterial scaffold is designed to provide physical cues to stem cells in order to promote their behavior for tissue formation. Recent work that explores the effect of scaffold physical properties, topography, mechanical properties and electrical properties, is discussed. Although still being elucidated, the biological mechanisms, including cell shape, focal adhesion distribution, and nuclear shape, are presented. This review also discusses emerging areas and challenges in clinical translation.

    more » « less