Cleavable Silyl Ether Monomers with Elevated Thermomechanical Properties for Bone Regeneration

Over the last years, stereolithography has developed to be one of the most promising fabrication techniques in tissue engineering. Posing the possibility of fabricating patient-specific, porous implants, it became especially attractive for scaffold fabrication for the treatment of critical sized bone defects. State-of-the-art photopolymer systems mostly consist of potentially cytotoxic compounds, such as (meth)acrylates, that furthermore show insufficient degradation and lead to acidic degradation products that could induce adverse tissue reactions. Herein, we introduced trifunctional monomers comprising cleavable silyl ether groups for thiol-ene photopolymerization to enlarge the material platform for printed bone grafts. Polymer networks comprising a high number of silyl ether moieties typically tend to be mechanically weak and exhibit low T_g values, especially when combined with thioether bonds, which are a direct result of polymerization via thiol-ene click reaction. To push thermomechanical properties to a level where they are sufficient for bone grafting (T_g > 37 °C), we introduced rigid bridged alicyclic structures in the form of norbornane-derived motifs into the silyl ether monomers, resulting in a norbornene-containing double bond monomer and a norbornane-derived thiol monomer. Together with noncleavable comonomers, we were able to demonstrate a substantial increase in T_g up to 62 °C, which is well above the values reported until now for similar thiol-ene networks. Furthermore, in this study, we demonstrated high photoreactivity for some of the monomers and also successfully performed proof-of-concept printing using a DLP setup. Besides excellent thermomechanical behavior, the mechanical strength of the silyl ether-based polymer network was shown to be outstanding. Cleavability of the silyl ethers was displayed with a quasi-linear degradation rate of 6.5% per month with moderate swelling. Additionally, the degradation product of the silyl ether-based network was isolated and shown to exhibit no relevant cytotoxicity to mouse fibroblast cells.