Synthesis and characterization of bioresorbable in situ crosslinkable ultra low molecular weight poly(lactide) macromer.

Reactive low molecular weight poly(L-lactide) (PLA) is required to produce in situ hardened scaffolds with fast rate of crosslinking, high crosslink density, and adequate mechanical strength. The objective of this work was to synthesize unsaturated ultra low molecular weight PLA (ULMW PLA) as an injectable in situ crosslinkable macromer for biomedical applications. Low molecular weight PLA was synthesized by ring-opening polymerization of L-lactide (LA) using diethylene glycol (DEG) as the initiator. The molar ratio of the LA to DEG ranged from 5 to 20. Non-solvents methanol, ether, and hexane were used for purification and fractionation. The PLA samples that were precipitated in methanol and ether had narrow distributions (PDI=1.2) and resulted in a powder with M(n) of 4.8 and a wax with M(n) of 3.6 kDa, respectively. The PLA sample in which the supernatant from ether was re-precipitated in hexane produced a viscous ULMW PLA with M(n) and PDI of 1.2 kDa and 1.2, respectively. The ULMW PLA was reacted with fumaryl chloride to produce unsaturated in situ crosslinkable poly(lactide fumarate) (PLAF) macromer. Porous scaffolds were produced after injection and in situ crosslinking of the PLAF macromer with NVP crosslinker in the presence of a porogen. New bone was formed in the scaffold when it was implanted in nude mice which demonstrated that the scaffold was osteoconductive. PLAF is potentially useful as a reactive macromer in fabrication of bioresorbable injectable in situ crosslinkable scaffolds for tissue regeneration.