A Multicomponent Bioactive Tissue-Engineered Blood Vessel: Fabrication, Mechanical Evaluation and Biological Evaluation with Physiological-Relevant Conditions

The high long-term failure rate of synthetic vascular grafts in the replacement of small vessels is known to be associated with the lack of physiological signals to vascular cells causing adverse hemodynamic, inflammatory or coagulatory events. Current studies focus on developing engineered vascular devices with ability of directing cell activity in vitro and in vivo for tissue regeneration. It is also known that controlled molecule release from scaffolds can dramatically increase the scaffold ability of directing cell activities in vitro and in vivo for tissue regeneration. To address the mechanical and biological problems associated with graft materials, we demonstrated a degradable polyester-fibroin composite tubular scaffolds which shows well-integrated nanofibrous structure, endothelial-conducive surface and anisotropic mechanical property, suitable as engineered vascular constructs. Tissue regeneration needs not only functional biomolecules providing signaling cues to cells and guide tissue remodeling, but also an adequate modality of molecule delivery. In fact, healthy tissue formation requires specific signals at well-defined place and time. To develop scaffolds with multi-modal presentation of biomolecules, we patterned electrospun nanofibers over the thickness of the 3-dimensional scaffolds by programming the deposition of interpenetrating networks of degradable polymers poly(ε-caprolactone) and poly(lactide-co-glycolide) acid in tailored proportion. Fluorescent model molecules, drug and growth factors were embedded in the polymeric fibers with different techniques and release profiles were obtained and discussed. Fabrication process resulted in precise gradient patterns of materials and functional biomolecules throughout the thickness of the scaffold. These graded materials showed programmable spatio-temporal control over the release. Molecule release profiles on each side of the scaffolds were used to determine the separation efficiency of molecule delivery, which achieved >90% for proteins in 200µm scaffolds. Gradient-patterned scaffolds were also used to program simultaneous release of two proteins to the opposite sides of the scaffold and sequential release of proteins to a defined space, which further demonstrate the ability of patterned nanofibers to spatially and temporally confine sustained release. Moreover, results showed that temporal release kinetics could be altered by the structural patterns. Thus, the hierarchically-structured scaffolds presented here may enable development of novel multifunctional scaffolds with defined 3D dynamic microenvironments for tissue regeneration.