The Influence of Fibrous Elastomer Structure and Porosity on Matrix Organization

Fibrous scaffolds are finding wide use in the field of tissue engineering, as they can be designed to mimic many native tissue properties and structures (e.g., cardiac tissue, meniscus). The influence of fiber alignment and scaffold architecture on cellular interactions and matrix organization was the focus of this study. Three scaffolds were fabricated from the photocrosslinkable elastomer poly(glycerol sebacate) (PGS), with changes in fiber alignment (non-aligned (NA) versus aligned (AL)) and the introduction of a PEO sacrificial polymer population to the AL scaffold (composite (CO)). PEO removal led to an increase in scaffold porosity and maintenance of scaffold anisotropy, as evident through visualization, mechanical testing, and mass loss studies. Hydrated scaffolds possessed moduli that ranged between ∼3-240 kPa, failing within the range of properties (<300 kPa) appropriate for soft tissue engineering. CO scaffolds were completely degraded as early as 16 days, whereas NA and AL scaffolds had ∼90% mass loss after 21 days when monitored in vitro. Neonatal cardiomyocytes, used as a representative cell type, that were seeded onto the scaffolds maintained their viability and aligned along the surface of the AL and CO fibers. When implanted subcutaneously in rats, a model that is commonly used to investigate in vivo tissue responses to biomaterials, CO scaffolds were completely integrated at 2 weeks, whereas ∼13% and ∼16% of the NA and AL scaffolds, respectively remained acellular. However, all scaffolds were completely populated with cells at 4 weeks post-implantation. Polarized light microscopy was used to evaluate the collagen elaboration and orientation within the scaffold. An increase in the amount of collagen was observed for CO scaffolds and enhanced alignment of the nascent collagen was observed for AL and CO scaffolds compared to NA scaffolds. Thus, these results indicate that the scaffold architecture and porosity are important considerations in controlling tissue formation.