Proangiogenic scaffolds as functional templates for cardiac tissue engineering

TLDR

The study presents a cardiac tissue‑engineering strategy that organizes multicellular components and provides directional cues to rebuild functional heart muscle architecture. The authors micro‑template a poly(2‑hydroxyethyl methacrylate‑co‑methacrylic acid) hydrogel scaffold with parallel channels and porous architecture, seed it with human ES‑cell‑derived cardiomyocytes, and culture it in vitro to promote organized tissue formation. Cardiomyocytes survived and proliferated to adult densities in the scaffold, while acellular scaffolds with 30–40 µm pores promoted angiogenesis, reduced fibrosis, and shifted macrophages to an M2 phenotype, demonstrating a platform for spatially controlled cardiac tissue engineering.

Abstract

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30–40 μm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.