Low-Initial-Modulus Biodegradable Polyurethane Elastomers for Soft Tissue Regeneration

The mechanical match between synthetic scaffold and host tissue remains challenging in tissue regeneration. The elastic soft tissues exhibit low initial moduli with a J-shaped tensile curve. Suitable synthetic polymer scaffolds require low initial modulus and elasticity. To achieve these requirements, random copolymers poly­(δ-valerolactone-co-ε-caprolactone) (PVCL) and hydrophilic poly­(ethylene glycol) (PEG) were combined into a triblock copolymer, PVCL–PEG–PVCL, which was used as a soft segment to synthesize a family of biodegradable elastomeric polyurethanes (PU) with low initial moduli. The triblock copolymers were varied in chemical components, molecular weights, and hydrophilicities. The mechanical properties of polyurethanes in dry and wet states can be tuned by altering the molecular weights and hydrophilicities of the soft segments. Increasing the length of either PVCL or PEG in the soft segments reduced initial moduli of the polyurethane films and scaffolds in dry and wet states. The polymer films are found to have good cell compatibility and to support fibroblast growth in vitro. Selected polyurethanes were processed into porous scaffolds by a thermally induced phase-separation technique. The scaffold from PU–PEG_1K–PVCL_6K had an initial modulus of 0.60 ± 0.14 MPa, which is comparable with the initial modulus of human myocardium (0.02–0.50 MPa). In vivo mouse subcutaneous implantation of the porous scaffolds showed minimal chronic inflammatory response and intensive cell infiltration, which indicated good tissue compatibility of the scaffolds. Biodegradable polyurethane elastomers with low initial modulus and good biocompatibility and processability would be an attractive alternative scaffold material for soft tissue regeneration, especially for heart muscle.