Development of an in-process UV-crosslinked, electrospun PCL/aPLA-co-TMC composite polymer for tubular tissue engineering applications

Abstract

Cardiovascular diseases remain the largest cause of death worldwide, and half of these deaths are the result of failure of the vascular system. Tissue engineering promises to provide new, and potentially more effective therapeutic strategies to replace damaged or degenerated vessels with functional vessels. However, these engineered vessels have substantial performance criteria, including vessel-like tubular shape, structure and mechanical property slate. Further, whether implanted without or with prior in vitro culture, such tubular scaffolds must provide a suitable environment for cell adhesion and growth and be of sufficient porosity to permit cell colonization. This study investigates the fabrication of slowly degradable, composite tubular polymer scaffolds made from polycaprolactone (PCL) and acrylated l-lactide-co-trimethylene carbonate (aPLA-co-TMC). The addition of acrylate groups permits the ‘in-process’ formation of crosslinks between aPLA-co-TMC chains during electrospinning of the composite system, exemplifying a novel process to produce multicomponent, elastomeric electrospun polymer scaffolds. Although PCL and aPLA-co-TMC were miscible in a co-solvent, a criteria for electrospinning, due to thermodynamic incompatibility of the two polymers as melts, solvent evaporation during electrospinning drove phase separation of these two systems, producing ‘core-shell’ fibres, with the core being composed of PCL, and the shell of crosslinked elastomeric aPLA-co-TMC. The resulting elastic fibrous scaffolds displayed burst pressures and suture retention strengths comparable with human arteries. Cytocompatibility testing with human mesenchymal stem cells confirmed adhesion to, and proliferation on the three-dimensional fibrous network, as well as alignment with highly-organized fibres. This new processing methodology and resulting mechanically-robust composite scaffolds hold significant promise for tubular tissue engineering applications. Statement of SignificanceAutologous small diameter blood vessel grafts are unsuitable solutions for vessel repair. Engineered solutions such as tubular biomaterial scaffolds however have substantial performance criteria to meet, including vessel-like tubular shape, structure and mechanical property slate. We detail herein an innovative methodology to co-electrospin and ‘in-process’ crosslink composite mixtures of Poly(caprolactone) and a newly synthesised acrylated-Poly(lactide-co-trimethylene-carbonate) to create elastomeric, core-shell nanofibrous porous scaffolds in a one-step process. This novel composite system can be used to make aligned scaffolds that encourage stem cell adhesion, growth and morphological control, and produce robust tubular scaffolds of tunable internal diameter and wall thickness that possess mechanical properties approaching those of native vessels, ideal for future applications in the field of vessel tissue engineering.