Speaker
Description
Introduction:
Injectability is one of the most desirable features of biomaterials. The combination of injectability and photocuring can provide materials to be easily and safely delivered using minimally invasive procedures. This is especially important for tissue sealants which allow to exclude the use of sutures or staples or for patches supporting the weakened tissue. Therefore, the aim of presented work is to create new injectable amphiphilic polymer-polymer hybrid system, which can be UV-cured in situ in vivo to form flexible patches for soft tissue regeneration. Such systems, with sufficient adhesive properties can be used without the need of using sutures or tacks and by applying them via minimally invasive procedures to provide support for the tissue.
Materials and Methods:
The polymer-polymer hybrid networks were prepared from fatty acid-modified precursors (Pr) bearing methacrylic groups and from PEGylated fibrinogen. For the synthesis of telechelic fatty acid-based macromonomers, three catalytic systems were tested: bismuth tris(2-ethylhexanoate) (BiHex) and zinc (II) acetyloacetonate (ZnAc), both in 4 mol%, and organo-Mg-Ti catalyst (1 mol%). The obtained liquid monomers were characterized by NMR and GPC. The UV-curing has been performed at the wavelength λmax of 385 nm (LED source) turning the liquids into flexible solids with use of 2% w/w photoinitiator (Omnirad 819). The gel fraction has been determined by refluxing materials in DCM. Cytotoxicity tests were performed on extracts using L929 cell line. Cell viability was then assessed using light microscopy and the resazurin viability assay on samples UV-cured in air and in argon. The PEG-ylation of fibrinogen was performed in two steps. In the first step, fibrinogen was dissolved in 50mM PBS with 8M urea (protein concentration 7mg/ml) and TCEP HCl was added and then stirred for 2h. After that, PEG-DA 4kDa was added (145:1 PEG-DA: fibrinogen) and reaction was continued overnight. Obtained product was purified and characterized by NMR (Bruker DPX HD-400 MHz). The hybrid was prepared using telechelic macromonomers and PEG-ylated fibrinogen with photoinitiator followed by solvent evaporation. Photocuring was performed in air atmosphere with use of the same UV-light source.
Results and Discussion:
New catalytic systems allowed to obtain telechelic macromonomers at the shortest reaction times for bismuth (7h) and magnesium-titanium catalysts (9h). Rection yield was similar for all of the materials (65-57%). The cell viability study showed that the use of nontoxic catalysts resulted in high cell viability, regardless of gel fraction. PEGylation of fibrinogen has reached high yield of 88%. The use of co-solvents, here ethyl acetate and/or dichloromethane and/or dimethylsulfoxide allowed to prepare amphiphilic hybrids. Their characteristics and adhesive properties will be discussed during the lecture.
Conclusions:
Photocurable macromonomers were synthesized with new catalysts, being non-toxic as revealed by high cell viability. The use of co-solvents allowed to prepare amphiplilic networks from hydrophobic macromonomer and hydrophilic PEGylated fibrinogen with the use of UV light. Obtained hybrid networks showed also high cell viability and elastomeric properties thus manifesting their suitability as patches for soft tissue engineering.
Acknowledgements:
This work has been financially supported by Polish National Science Center (Grant number: UMO-2019/33/B/ST5/01445).
73296353379
