In vitro cardiac tissue models: Current status and future prospects

Abstract

Cardiovascular disease is the leading cause of death worldwide. Achieving the next phase of potential treatment strategies and better prognostic tools will require a concerted effort from interdisciplinary fields. Biomaterials-based cardiac tissue models are revolutionizing the area of preclinical research and translational applications. The goal of in vitro cardiac tissue modeling is to create physiological functional models of the human myocardium, which is a difficult task due to the complex structure and function of the human heart. This review describes the advances made in area of in vitro cardiac models using biomaterials and bioinspired platforms. The field has progressed extensively in the past decade, and we envision its applications in the areas of drug screening, disease modeling, and precision medicine.

Keywords: Biomaterials; Cardiac tissue models; Disease modeling; Drug screening; In vitro cardiac tissue engineering; Regenerative medicine; Tissue engineering.

Figure 1

Overview of in vitro cardiac tissue model. New in vitro biomaterial-based cardiac tissue models have the potential to be used for fundamental research and translational applications. In particular, the areas of drug discovery, disease modeling, and precision medicine could benefit immensely from these emerging technologies.

Figure 2

Micropatterned 2D cardiac models. Topographical alignment of CMs with (A) microfabricated nanostructured surface [50]; (B) prestressed thermoplastic shrink film with tunable multi-scaled wrinkles [49]; and (C) microcontact-printed patterns of pattern CMs into (D) aligned stripes to mimic adult cardiac tissue structure [55] and (E) circular colonies for high-throughput screening [64]. (F) Using oxygen plasma to etch PEG surfaces under a PDMS stencil protection allows micropatterning hiPSCs and determining stem cell fate during cardiac differentiation [72].

Figure 3

Biomaterial-based 3D cardiac models. (A) Engineered heart mini-tissues (millimeter scale) were made from fibrin and hiPSCs for implantation [78] and drug-screening purpose [79]. (B) Engineered heart micro-tissue (micron scale) made from collagen were used to model the dilated cardiomyopathy caused by titin mutation [82]. (C) Fibrin-based cardiac tissue patch was generated by soft lithography with controllable size and architecture and its drug response to isoproterenol [85]. (D) A biowires platform combining architectural and electrical cues generated a microenvironment conducive to the maturation of hiPSC-derived cardiac tissues [95]. (E) Electrospun nanofiber scaffolds were made for creating the continuous anisotropic cardiac tissue [89]. (F) Aligned nanofiber scaffolds made by rotary jet spinning promoted better sarcomere formation in CMs [91]. (G) High-defined filamentous scaffolds made by two-photon initiated polymerization were used to create an aligned hiPSC-CMs-based cardiac model for drug screening [92].

Figure 4

Microdevice-based 3D cardiac models. (A) PIPAAm-based ‘heart-on-chip’ microsystem [97] can measure the deformation of the elastomeric thin film to characterize the contractility of cardiac tissue derived from various cell types and assess the drug response to isoproterenol [98]. (B) A stacked-paper culture system containing CMs was used to mimic the pathological microenvironment occurring during cardiac ischemia [101]. (C) A microfluidic-based microphysiological system was designed to recapitulate a minimal organoid of the human myocardium with highly aligned tissue architecture and anisotropic beating behavior, allowing for accurate prediction of drug cardiotoxicity [102].