Proangiogenic scaffolds as functional templates for 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. Surfacemodified 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.angiogenesis | cardiomyocyte | human embryonic stem cell | hydrogel

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

“…In recent literature, higher ratios of M2/M1 macrophages concomitantly with an absence of a foreign body response have been found with scaffolds having 30-40-mm pores when compared to hosts with nonporous implants. 47 In this study, TiO 2 -HAP-GEL scaffolds had 34% porosity with 1.52 -0.8-mm pores and were not engineered in vitro as in other studies 48 reporting a M1 predominant immune response (to engineered in vitro matrices); therefore, we would expect to have no foreign body response and a predominant M2 macrophage activity. Moreover, human MAPCs were recently found safe for clinical trials for treatment of graftversus-host disease (ClinicalTrials.gov NCT00677859, NCT00677222).…”

The Biocompatibility Manifesto: Biocompatibility for the Twenty-first Century

“…This pore structure allowed us to accurately assess the effect of pore size on the FBR. We found that when the pores were 30-40 μm in diameter, there was considerable angiogenesis and much reduced capsule formation (loose, open collagen fibrils, in contrast to highly oriented, dense collagen) [24][25][26][27]. When pores were larger or smaller, the classic FBR was observed.…”

“…The solid slab will heal with the classic FBR, a dense capsule surrounding the implant. The same polymer with 30-μm pores will show little or no fibrosis, excellent vascularization, and reconstruction of the original tissue [25]. We have in the two specimens described here the same biomaterial used in the same specific application.…”

“…However, these sphere-templated polymers do not degrade to bioactive fragments like SIS. We believe they function by mechanically guiding the macrophage, because of the confinement within the pores, to a pro-regenerative phenotype (often called M2) in contrast to a pro-inflammatory phenotype (M1) [25,28,29]. In the case of the SIS and sphere-templated polymer, by controlling the fate of the macrophage, the FBR is deflected, and regenerative healing occurs.…”

Hydrogels for Cardiac Tissue Repair and Regeneration

“…In one study, it was used a fi brin patch seeded with swine kDa and it can be crosslinked in the presence of calcium ions to form a gel structure and has recently been applied in myocardial tissue engineering, as an injectable cell delivery vehicle [48][49][50][51]. Due to its biocompatibility has been approved by FDA for human use as wound dressing material [52].…”