Design Approaches to Myocardial and Vascular Tissue Engineering

Abstract

Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.

Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with Therapeutic Potential

“…This hydrogel-based, responsive depot is promising for the controlled delivery of FGF-2 in a number of biomedical applications, such as cardiovascular tissue engineering and vascular graft surgeries: release profiles that are sustained (in healthy tissues), responsive (in GSH-enriched tissues), or pulsatile (upon application of light) can be achieved to drive a variety of cellular processes when and where needed. [34] The presented approach could also be easily translated for the release of other heparin-binding proteins of comparable molecular weight and heparin binding affinity, such as the immune activating cytokine IL-2. [17, 18] In summary, the results of our study indicate that incorporation of receptor-host interactions along with chemistries that respond to endogenous and exogenous stimuli can be utilized to control the release of low molecular weight proteins.…”

3D bioprinting for cardiovascular regeneration and pharmacology

“…The blood vessels have complex unique structures in multi-scale and multilayer arrangements in this complex tissue. The inner diameters of blood vessels range from microscopic size, ~5–10μm for the smallest capillaries, to 30mm, for the largest artery (aorta) [16,51]. On the cellular level, a mammalian heart is composed of ≈20% to 30% CMs (roughly 75% of the heart volume) and 70% to 80% nonmyocytes (ECs, SMCs, and fibroblasts (FBs)) [2,15,52].…”

“…An alternative interventional approach involves stem cell therapy, such as cell injection into the myocardium. This approach is surgically less invasive, but has been shown to have low viability and weak host cell integration [51,58–60]. Therefore, there is an urgent need to address these challenges to effective CVD treatment through the development of new therapeutic strategies.…”

“…Although some additional techniques such as biomechanical stimulation and/or electrical stimulation have been applied to improve 2D cultures, they lack many essential anatomical and physiological features of cardiovascular micro-environments. Thereby, these 2D culturing methodologies fail to offer an effective strategy for regenerating cardiac tissue and by extension, are not suitable for developing disease model/drug screening platforms [2,12,51]. …”

“…Hemodynamics are an essential epigenetic factor in the development of the electrical conduction (His-Purkinje) system in the heart [51,146,149]. Many studies have compared static and perfusable culture conditions during the generation of various vascularized constructs, especially for engineered cardiac tissue.…”