Developing biomaterials with non-linear elasticity using core/shell electrospinning technology

One of the major challenges in the field of biomaterials engineering is the replication of the non-linear elasticity of soft tissues. In this PhD thesis project, non-linearly elastic biomaterials have been successfully fabricated from a chemically cross-linked elastomeric poly (glycerol sebacate) (PGS) and thermoplastic poly (L-lactic acid) (PLLA) or polyvinyl alcohol (PVA). PGS/PLLA fibre mats were fabricated using the core/shell electrospinning technique and the spun fibrous materials, containing a PGS core and PLLA shell, demonstrated J-shaped stress-strain curves, having ultimate tensile strength, rupture elongation, and stiffness constants comparable to muscle tissue properties. In vitro evaluations have shown that the PGS/PLLA fibrous biomaterials possess excellent biocompatibility, and are capable of supporting human stem-cell-derived cardiomyocytes over several weeks in culture or supports, and they can foster the growth of enteric neural crest (ENC) progenitor cells. Controlled enzymatic degradation is a major requirement of polyester implants in vivo and excessively rapid degradation speed is the major drawback for PGS. In vitro degradation of PGS/PLLA core/shell fibre mats were explored in tissue culture medium with and without enzyme, and were compared with cast PGS sheets. Both pH change and weight loss results have proved that the degradation rates of these core/shell fibre mats are much slower than PGS sheet in media with or without enzyme. It has been previously shown that aligned fibre mats can guide neurite and stem cell growth along the aligned fibres. Therefore in this project, aligned PGS/PLLA core/shell fibre mats collected on a rotating drum under different rotational speeds were fabricated, and their alignment and mechanical properties measured. The stiffness of fibre mats dramatically increased with higher rotation speed, while UTS elongation and resilience initially increased with the degree of alignment, but then decreased. PLLA cannot be easily removed by solvent dissolution and so pure PGS fibre mats could not be obtained from PGS/PLLA core/shell fibre mats. However more pure PGS porous mats were fabricated by dissolution of the water soluble poly (vinyl alcohol) shell surrounding the PGS core in core-shell electrospun fibres, and these mats were studied. For these experiments, a different PGS was synthesized with a stoichiometric glycerol:sebacic acid ratio of 2:3 (rather than the more common 1:1 ratio) and it was found that this overcame the rapid degradation kinetics normally found with 1:1 PGS. Tensile tests showed these porous PGS2:3 mats had superior mechanical properties than cast PGS2:3 polymers and they demonstrated J-shaped stress-strain curves when tested in the wet state. In vitro evaluations revealed that the spun porous PGS2:3 have excellent biocompatibility.