Nanofibrous polyester-polypeptide block copolymer scaffolds with high porosity and controlled degradation promote cell adhesion, proliferation and differentiation

The nanofibrous ultrastructure of native extracellular matrix (ECM) provides topological cues for specific cellular behavior, therefore, serves as a physical template for bio-scaffolds design and fabrication. Poly(gamma-benzyl-cglutamate) (PBLG) is a commonly used polypeptide, which often self-assembles into nanofibers. However, the slow degradation of PBLG limits its application in tissue engineering. Herein, poly(D,L-lactide)-b-poly(gamma-benzyl-cglutamate) (PDLLA-b-PBLG) was successfully synthesized. This polyester-polypeptide copolymer underwent nanofibrous self-assembly through quenched thermally induced phase separation (TIPS) and alpha-helix formation of PBLG segment. It was noted that this block copolymer degraded much faster than PBLG homopolymer, since the degradation mostly occurred to PDLLA segments. A three-dimensional PDLLA-b-PBLG scaffold was then obtained with larger nanofiber sizes and higher porosity than the PBLG scaffold, which was highly cytocompatible and conducive to cell adhesion, spreading and proliferation. For neural tissue engineering applications, the copolymer scaffold was found capable of facilitating neural stem cells differentiation into neuron-like cells. These results suggested that the scaffolds fabricated from PDLLA-b-PBLG with nanofibrous structures held great potential for stem cell transplantation and neural tissue engineering.