Biomaterial property-controlled stem cell fates for cardiac regeneration

Abstract

Myocardial infarction (MI) affects more than 8 million people in the United States alone. Due to the insufficient regeneration capacity of the native myocardium, one widely studied approach is cardiac tissue engineering, in which cells are delivered with or without biomaterials and/or regulatory factors to fully regenerate the cardiac functions. Specifically, in vitro cardiac tissue engineering focuses on using biomaterials as a reservoir for cells to attach, as well as a carrier of various regulatory factors such as growth factors and peptides, providing high cell retention and a proper microenvironment for cells to migrate, grow and differentiate within the scaffolds before implantation. Many studies have shown that the full establishment of a functional cardiac tissue in vitro requires synergistic actions between the seeded cells, the tissue culture condition, and the biochemical and biophysical environment provided by the biomaterials-based scaffolds. Proper electrical stimulation and mechanical stretch during the in vitro culture can induce the ordered orientation and differentiation of the seeded cells. On the other hand, the various scaffolds biochemical and biophysical properties such as polymer composition, ligand concentration, biodegradability, scaffold topography and mechanical properties can also have a significant effect on the cellular processes.

Keywords: Biomaterials; Cardiac differentiation; Cardiac tissue engineering; Myocardial infarction; Stem cell fate.

Graphical abstract

Fig. 1

An overview of cell encapsulated scaffold-based cardiac tissue engineering process: Cells are seeded into scaffolds made of natural-derived or synthetic polymers, and the tissue constructs are then cultured in vitro under specific conditions to develop into mature tissues before implantation in vivo.

Fig. 2

Biochemical and biophysical microenvironment properties that affect the fate of transplanted stem cells .

Fig. 3

Matrix elasticity (A) and differentiation of seeded naive MSCs (B) .

Fig. 4

Different cell cardiac differentiation extents, as indicated by protein expressions of CX43 (b,e) and CTnI (c,f) were observed in CDCs seeded in scaffolds with different fiber densities, fiber orientations and mechanical properties (a, d) .

Fig. 5

Use of biodegradable (a) hydrogels based on NIPAAm, AAc and HEMAPTMC for the treatment of MI. (b) Increased LV wall thickness and capillary density were observed 8 weeks after gel injection; (c) H&E staining; (d) Immunohistochemical staining (blue: nuclear, green: α-SMA). Both of the images indicated the infiltration of cells into the hydrogels (black dots are the injected hydrogel area) .