Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering

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.

Biofabrication of Collagen Tissue-Engineered Blood Vessels with Direct Co-Axial Extrusion

“…An important consideration to take into account for TEBV development is the mimicking of the extracellular matrix composition [ 18 ]. In this study, we aimed to extrude TEBVs with high concentration of collagen type I as the unique biomaterial composition, to assess if vascular cells were able to survive within them and if they had enough mechanical properties to withstand perfusion equivalent to arterial shear stress.…”

Progress in Bioengineering Strategies for Heart Regenerative Medicine

“…Biomaterial-based strategies for tissue engineering have recently attracted much attention in cardiac biology and medicine, since they are known to be effective for not only promoting the maturation of hPSC-CMs in vitro but also improving the cardiac regenerative effects of cell-based and/or cell-free therapies against heart disease models in vivo [ 11 , 12 ]. Biomaterials, represented by hydrogels and decellularized scaffolds, have various advantages for regenerative therapies, including enhancing cell survival and cell retention/engraftment into the host tissue; promoting protective paracrine signaling responses by containing and releasing functional bioactive molecules such as angiogenic, anti-apoptotic, and/or immunomodulatory factors; and providing mechanical support for the damaged tissues [ 64 , 67 , 68 ]. Ideal biomaterials in tissue engineering are usually considered as being biocompatible, biodegradable, less immunogenic, and biomimetic products resembling properties of the target native tissue.…”

“…Other concerns around the use of biomaterial-based hydrogels include low availability of the required clinical-grade biomaterials, batch–batch variability, difficulty for sterilization and standardization operating procedures, and uncertainty of the optimal time window and delivery route. For a more in-depth review about this subject, we direct the readers to other reviews [ 67 , 124 , 125 , 126 ].…”

“…Although such personalized bioengineering technologies and medicine are expected to become reality in the near future, continuous efforts are needed to assure the accuracy, relevance, reproducibility, and robustness in these engineered technologies and constructs. Since the cardiac tissue engineering field holds interdisciplinary aspects, the clinical translation and medical application of the engineered heart tissues will require tight collaborations across many disciplines, involving stem cell biology, material science, biofabrication technology, cardiovascular medicine, and also business administration [ 67 , 68 , 237 ].…”

A Biohybrid Material With Extracellular Matrix Core and Polymeric Coating as a Cell Honing Cardiovascular Tissue Substitute

“…Cell seeding and in-vitro mechanical preconditioning were tried, but such attempts have also not yielded tangible outcomes that could improve their clinical translation ( 13 , 14 ). The failure mechanisms are often attributed to weak mechanical properties, residual detergents, and remnant cellular materials that cause structural degeneration and calcification and prevents active remodeling ( 15 – 17 ). Synthetic grafts made from polymers, such as Gore-Tex and Dacron, have gained significant use in the past few decades due to excellent mechanical properties, and some success in achieving hemocompatibility ( 2 , 3 , 18 ).…”