31 - Novel, Injectable, Biocompatible and Tunable Polymer for Vertebral Augmentation

The standard material used for vertebral augmentation is polymethyl methacrylate (PMMA) cement. Unfortunately, PMMA is stiffer than native bone, which is thought to contribute to adjacent level fractures in treated patients. The purpose of this project was to develop a novel injectable polymer with tunable mechanics to match bone stiffness to mitigate adjacent fracture risk as well as provide a substrate for new bone growth.

Materials and Methods:

Poly(allyl glycidyl ether succinate) (PAGES) was synthesized via ring-opening copolymerization of succinic anhydride and allyl glycidyl with a propargyl alcohol initiator and then crosslinked with 3-mercaptopropionate. BaSO₄, SrCO₃, or alpha tricalcium phosphate (αTCP) was added to make PAGES radio-opaque and increase strength. Different degrees of polymerization (chain lengths) were tested. Gelation time (analogous to setting time for PMMA) and compressive mechanical properties were determined. Rat mesenchymal stem cells were cultured for 17 days on thin layers of PAGES and stained for osteocalcin to determine osteogenesis. Statistical analysis was performed in Excel using t-tests or ANOVA.

Results: The length of PAGES polymers was adjusted to have clinically relevant cure times. Further testing was performed on polymers containing an average of either 29 or 48 monomers. Cure time for 29 monomer PAGES was found to range from 25 ± 4 to 49 ± 7 (average ± standard deviation) minutes compared to 39 ± 6 to 161 ± 24 minutes for 48 monomer PAGES at 25 C across different volumes of added crosslinker (N=3, p< 0.05). Cure times were significantly shorter at 37 C (N=3, p< 0.05). The peak stress of the 29 monomer PAGES was 1.9 ± 0.5 MPa at day 1 with a strain at break of 33.4 ± 3.5%. PAGES exhibited significant stiffening between Day 1 and Day 7.  The addition of 50% w/w BaSO₄ or SrCO₃ significantly increased ultimate stress for 29 monomer PAGES blocks (1.9 ± 0.5 MPa for no additive vs 3.3 ± 0.6 MPa for 50% SrCO₃, N=6, p< 0.001). The ultimate stress was similar to reported values for human vertebra (1-6 MPa), compared to 66-77 MPa for PMMA {1,2}  The addition of SrCO₃ also significantly increased the percentage of osteoblasts compared to no additive or BaSO₄ PAGES.

Conclusion: PAGES is a novel bone augmentation polymer with tunable properties that can allow it to better match the mechanical characteristics of native vertebral bodies and allow for improved biocompatibility, which could lead to improved long-term patient outcomes, particularly reduced adjacent-level fracture.