An Alternating Copolymer of Degradable Polar/Hydrophobic/Ionic Polyurethane for Improved Anti-Inflammatory Response

Zhao, Spencer 1, 2, 3 ; Battiston, Kyle G 1, 2, 4, 5 ; Santerre, J. Paul 1, 2, 5;

 1.  Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2.  Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research; 3.  Division of Engineering Science, University of Toronto; 4.  Polumiros, Inc.; 5.  Faculty of Dentistry, University of Toronto


The inflammatory response plays a critical role in the ability of biomaterials to function in vivo. A degradable polar/hydrophobic/ionic (D-PHI) polyurethane has been demonstrated to reduce pro-inflammatory immune cell activation. This ability is dependent on the presence of all three hydrophobic (methyl methacrylate, MMA), ionic (methacrylic acid, MAA) and polar (divinyl oligomer, DVO) D-PHI monomers. It is unknown if the monomer sequencing (random vs. alternating) is important in determining anti-inflammatory character. The similar electronic nature of DVO, MAA and MMA suggests propagation proceeds in a random order. However regular monomer order, and thus even distribution of chemical functionality, may be achieved through an alternating copolymerization.


The objective is to synthesize an alternating D-PHI copolymer using maleic acid (MA) (ionic) and ethyl vinyl ether (EVE) (hydrophobic), with opposite electrophilic and nucleophilic alkene functionality, and assess for its anti-inflammatory character relative to original D-PHI using an IgG marker assay.


Traditional D-PHI (DVO-MAA-MMA) and alternating copolymer formulations (DVO-MA-EVE) were synthesized using a UV light photopolymerization in five feed molar ratios 1:5:X respectively (X=15, 22.5, 30, 37.5, 45). Elemental analysis and ATR-FTIR were used to determine elemental composition and monomer ratios to characterize sequence structure. Elastic modulus was determined with compression testing. Immunomodulatory properties were tested with an immunoglobulin-G Fab-region specific ELISA.

Results & Discussion

Tripling the MMA:DVO molar feed ratio in DVO-MAA-MMA results in a 32.6±0.3% increase in relative MMA:DVO FTIR signal ratio; however in DVO-MA-EVE tripling the EVE:DVO ratio did not change the EVE:DVO signal ratio (99±5% of the original value). DVO-MAA-MMA possesses lower nitrogen content (1.59±0.14%) consistent with random stoichiometric addition of monomers whereas DVO-MA-EVE systems have higher nitrogen contents (2.73±0.16%), 1.5±0.1 times the upper limit for random addition Therefore, DVO-MA-EVE is believed to undergo a reaction selective for monomer order and possess regularly-spaced polar, hydrophobic and ionic functionalities while DVO-MAA-MMA undergoes a random polymerization. DVO-MA-EVE features a lower elastic modulus than DVO-MAA-MMA (1.18±0.26 vs.12.71±3.09MPa), possibly due to its higher molar DVO:non-DVO ratio. The ELISA results suggest a lower total Fab exposure (0.028±0.010, abs. units) in DVO-MA-EVE compared to DVO-MAA-MMA (0.115±0.016, abs. units).


D-PHI has been modified into an alternating copolymer using MA and EVE, in contrast with random-order DVO-MAA-MMA. The new material was found to have a lower Fab exposure, indicating potentially a lower inflammatory character, and a lower elastic modulus. Introduction of monomer sequence control could be a useful tool for modifying D-PHI chemistry to tailor interactions with immune cells.