ECM roles and biomechanics in cardiac tissue decellularization.

Natural biomaterials hold enormous potential for tissue regeneration. The rapid advance of several tissue-engineered biomaterials, such as natural and synthetic polymer-based scaffolds, has led to widespread application of these materials in the clinic and in research. However, biomaterials can have limited repair capacity; obstacles result from immunogenicity, difficulties in mimicking native microenvironments, and maintaining the mechanical and biochemical (i.e., biomechanical) properties of native organs/tissues. The emergence of decellularized extracellular matrix (ECM)-derived biomaterials provides an attractive solution to overcome these hurdles since decellularized ECM provides a nonimmune environment with native three-dimensional structures and bioactive components. More importantly, decellularized ECM can be generated from the tissue of interest, such as the heart, and keep its native macro- and microstructure and tissue-specific composition. These decellularized cardiac matrices/scaffolds can then be reseeded using cardiac cells, and the resulting recellularized construct is considered an ideal choice for regenerating functional organs/tissues. Nonetheless, the decellularization process must be optimized and depends on tissue type, age, and functional goal. Although most decellularization protocols significantly reduce immunogenicity and deliver a matrix that maintains the tissue macrostructure, suboptimal decellularization can change ECM composition and microstructure, which affects the biomechanical properties of the tissue and consequently changes cell-matrix interactions and organ function. Herein, we review methods of decellularization, with particular emphasis on cardiac tissue, and how they can affect the biomechanics of the tissue, which in turn determines success of reseeding and in vivo viability. Moreover, we review recent developments in decellularized ECM-derived cardiac biomaterials and discuss future perspectives.

Novel Techniques Targeting Fibroblasts after Ischemic Heart Injury.

The great plasticity of cardiac fibroblasts allows them to respond quickly to myocardial injury and to contribute to the subsequent cardiac remodeling. Being the most abundant cell type (in numbers) in the heart, and a key participant in the several phases of tissue healing, the cardiac fibroblast is an excellent target for treating cardiac diseases. The development of cardiac fibroblast-specific approaches have, however, been difficult due to the lack of cellular specific markers. The development of genetic lineage tracing tools and Cre-recombinant transgenics has led to a huge acceleration in cardiac fibroblast research. Additionally, the use of novel targeted delivery approaches like nanoparticles and modified adenoviruses, has allowed researchers to define the developmental origin of cardiac fibroblasts, elucidate their differentiation pathways, and functional mechanisms in cardiac injury and disease. In this review, we will first characterize the roles of fibroblasts in the different stages of cardiac repair and then examine novel techniques targeting fibroblasts post-ischemic heart injury.