New block copolymers to form nanofibers with superior mechanical properties and to conjugate signaling molecules directing tissue regeneration

Abstract

Tissue engineering is a multidisciplinary field grown rapidly over the past few decades, whose success most often requires bioactive scaffolds to structurally support and biologically direct cell fate and tissue regeneration. Poly(l-lactic acid) (PLLA) is a widely used tissue engineering material with high strength, biocompatibility, biodegradability, and the capability of nanofiber formation through thermally induced phase separation (TIPS). To enable biomolecule conjugation, a new PLLA-based block copolymer, poly(spiro-lactic-co-lactic acid)-block-poly(l-lactic acid) or PSLA-b-PLLA, was developed in this study. The new polymer PSLA-b-PLLA could also form nanofibers through TIPS, and excitingly greatly improved the mechanical properties over PLLA nanofibers, with up to 1.2 times tensile modulus, 12.1 times strain at break, 2.1 times ultimate strength and 35.1 times toughness of PLLA, while being able to conjugate bioactive molecules covalently using click reactions. Its degradation rate was also accelerated to facilitate tissue regeneration. The tissue engineering potential of the new polymer scaffold was evaluated using a mouse critical-sized bone regeneration model, showing 3.6 times more vascularized bone volume regeneration when covalently conjugated with a bone-morphogenetic-protein-2-derived peptide. The block copolymer satisfies multiple criteria for tissue engineering with tunable mechanical properties, degradation rate, and conjugation densities. It can be utilized to impart specific biomolecular signals and mechanical properties potentially for various other tissue engineering applications.