Multivalent network modifier upregulates bioactivity of multispecies biofilm-resistant polyalkenoate cement

Polyalkenoate cement (PAC) is a promising material for regenerative hard tissue therapy. The ionically rich glass component of PAC encourages bioactive interaction via. the release of essential ions. However, PAC bioactivity is restricted owing to (i) structurally inherent cationic network formers and (ii) surface bacterial biofilm formation. These two factors cause a deficiency in ion release, further complicated by secondary infections and premature therapeutic failure. Here, a multivalent zwitterionic network modifier (mZM) is presented for upregulation of ionic exchange and bioactivity enhancement. By introducing a non-zero charged mZM into PACs, an increase in the proportion of non-bridging oxygen occurs. The network modification promotes ion channel formation, causing a multiple-fold increase in ion release and surface deposition of hydroxy-carbonate apatite (ca. 74%). Experiments ex vivo and animal models also demonstrate the efficient remineralization ability of the mZM. Furthermore, divalent cationic interaction results in bacterial biofilm reduction (ca. 68%) while also influencing a shift in the biofilm species composition, which favors commensal growth. Therefore, PAC modification with mZM offers a promising solution for upregulation of bioactivity, even aiding in customization by targeting site-specific regenerative therapy in future applications.