Molecularly engineered biodegradable polymer networks with a wide range of stiffness for bone and peripheral nerve regeneration

To satisfy different mechanical requirements in hard and soft tissue replacements, a series of biodegradable and crosslinkable copolymers of poly(propylene fumarate)-co-polycaprolactone (PPF-co-PCL) are synthesized and employed to fabricate 2D disks and 3D scaffolds via photocrosslinking. Thermal properties such as the glass transition temperature (T_g) and melting temperature (T_m) of the PPF-co-PCL networks can be controlled efficiently by varying the PCL composition (φ_PCL). As a result, their mechanical properties vary significantly from hard and stiff materials to soft and flexible ones with increasing φ_PCL, making them attractive candidate materials for bone and peripheral nerve regeneration, respectively. Several PPF-co-PCL formulations are selected to perform in vitro cell studies using mouse pre-osteoblastic MC3T3-E1, rat Schwann cell precursor line (SPL201), and pheochromocytoma (PC12) cells, and in vivo animal testing in the rat femur bone defect model and in the rat sciatic nerve transection model. The formation of new bone in the porous bone scaffolds with a low φ_PCL and guided axon growth through the nerve conduits with a higher φ_PCL suggest that crosslinked PPF-co-PCLs have appropriate compatibility and functionality. Furthermore, the role of surface stiffness in modulating cellular behavior and functions is verified on the crosslinked PPF-co-PCL surfaces without any pretreatments.