Customized Heparinized Alginate and Collagen Hydrogels for Tunable, Local Delivery of Angiogenic Proteins.

Therapeutic protein delivery has ushered in a promising new generation of disease treatment, garnering more recognition for its clinical potential than ever. However, proteins' limited stability, extremely short average half-lives, and evidenced toxicity following systemic delivery continue to undercut their efficacy. Biomaterial-based protein delivery, however, demonstrates the potential to overcome these obstacles.

Wet-Spun Polycaprolactone Scaffolds Provide Customizable Anisotropic Viscoelastic Mechanics for Engineered Cardiac Tissues.

Myocardial infarction is a leading cause of death worldwide and has severe consequences including irreversible damage to the myocardium, which can lead to heart failure. Cardiac tissue engineering aims to re-engineer the infarcted myocardium using tissues made from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to regenerate heart muscle and restore contractile function via an implantable epicardial patch. The current limitations of this technology include both biomanufacturing challenges in maintaining tissue integrity during implantation and biological challenges in inducing cell alignment, maturation, and coordinated electromechanical function, which, when overcome, may be able to prevent adverse cardiac remodeling through mechanical support in the injured heart to facilitate regeneration.

Stimulating Calcium Handling in hiPSC-Derived Engineered Cardiac Tissues Enhances Force Production.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have profound utility in generating functional human engineered cardiac tissues (ECT) for heart repair. However, the field at large is concerned about the relative immaturity of these hiPSC-CMs as we aim to develop clinically relevant models for regenerative therapy and drug testing. Herein, we develop a novel calcium (Ca2+) conditioning protocol that maintains ECTs in a physiological range of Ca2+ and assesses contractility in increasing calcium environments.

Engineering a collagen matrix for cell-instructive regenerative angiogenesis.

Engineering an angiogenic material for regenerative medicine requires knowledge of native extracellular matrix remodeling by cellular processes in angiogenesis. Vascularization remains a key challenge in the field of tissue engineering, one that can be mitigated by developing platforms conducive to guiding dynamic cell-matrix interactions required for new vessel formation. In this review, we highlight nuanced processes of angiogenesis and demonstrate how materials engineering is being used to interface with dynamic type I collagen remodeling, Notch and VEGF signaling, cell migration, and tissue morphogenesis.

Optimizing Blended Collagen-Fibrin Hydrogels for Cardiac Tissue Engineering with Human iPSC-derived Cardiomyocytes.

Natural polymer hydrogels are used ubiquitously as scaffold materials for cardiac tissue engineering as well as for soft tissue engineering more broadly because of FDA approval, minimal immunogenicity, and well-defined physiological clearance pathways. However, the relationships between natural polymer hydrogels and resident cell populations in directing the development of engineered tissues are poorly defined. This interaction is of particular concern for tissues prepared with iPSC-derived cell populations, in which population purity and batch-to-batch variability become additional critical factors to consider.