Biomaterial-driven in situ cardiovascular tissue engineering—a multi-disciplinary perspective

Abstract

There is a persistent and growing clinical need for readily-available substitutes for heart valves and small-diameter blood vessels. In situ tissue engineering is emerging as a disruptive new technology, providing ready-to-use biodegradable, cell-free constructs which are designed to induce regeneration upon implantation, directly in the functional site. The induced regenerative process hinges around the host response to the implanted biomaterial and the interplay between immune cells, stem/progenitor cell and tissue cells in the microenvironment provided by the scaffold in the hemodynamic environment. Recapitulating the complex tissue microstructure and function of cardiovascular tissues is a highly challenging target. Therein the scaffold plays an instructive role, providing the microenvironment that attracts and harbors host cells, modulating the inflammatory response, and acting as a temporal roadmap for new tissue to be formed. Moreover, the biomechanical loads imposed by the hemodynamic environment play a pivotal role. Here, we provide a multidisciplinary view on in situ cardiovascular tissue engineering using synthetic scaffolds; starting from the state-of-the art, the principles of the biomaterial-driven host response and wound healing and the cellular players involved, toward the impact of the biomechanical, physical, and biochemical microenvironmental cues that are given by the scaffold design. To conclude, we pinpoint and further address the main current challenges for in situ cardiovascular regeneration, namely the achievement of tissue homeostasis, the development of predictive models for long-term performances of the implanted grafts, and the necessity for stratification for successful clinical translation.

Cardiac Progenitor Cells: The Matrix Has You

“…One possible approach to repair the tissue in all its components is to provide an exogenous matrix as an ideal substrate and support for cell transplantation. Several biomaterials, either natural or synthetic, have been used as ECM substitutes thus far . Undoubtedly, collagen, gelatin, alginate, and fibrin are the most used among natural polymers, as they are naturally charged with numerous cell binding sites while ensuring high biocompatibility and biodegradability.…”

Fabrication, characterization, and in vitro evaluation of electrospun polyurethane‐gelatin‐carbon nanotube scaffolds for cardiovascular tissue engineering applications

“…Blending of polyurethane by natural biological polymer like gelatin is followed by two aims: (1) increment of biological properties of composite scaffolds especially for cell adhesion and proliferation, (2) adjusting biodegradation rate of the scaffolds to help effective formation of neo tissue (Baheiraei et al, ; Wissing, Bonito, Bouten, & Smits, ).…”

In situ Enabling Approaches for Tissue Regeneration: Current Challenges and New Developments

“…This approach takes advantage of the surrounding biological microenvironment, directing the fate of cells to regenerate new tissue without complicated prior in vitro cell manipulation . Several reviews can be found in the literature describing what is currently known about the mechanisms and strategies used to induce in situ cell differentiation and tissue regeneration (Chen et al, 2011;Yang et al, 2014;Talacua et al, 2015;Dhand et al, 2016;Murdock and Stephen, 2017;Wissing et al, 2017).…”