Final Report Summary - VINDOBONA (VINyl photopolymer Development Of BONe replacement Alternatives)
Summary
In this project, new photopolymers for use as potential bone replacement materials have been developed which can be fabricated by 3D printing. Since the material itself and its degradation products should exhibit very low cytotoxicity, acrylate based reactive diluents have been replaced by a new generation of monomers with exceptionally low toxicity (vinyl carbonates and vinyl esters). Making use of the exceptional coreactivity of these vinyl monomers with alkyl thiols, polymers may be formed rapidly as is the case with analogous acrylates and yet with improved mechanical properties and significantly reduced cytotoxicity. The influence of monomer structure and thiol concentration have been investigated along with suitable fillers like hydroxyapatite. This has allowed for the development of a new class of 3D printable material with mechanical properties similar to those of natural bone. In collaboration with biologists and health care professionals, additional in vitro testing has been conducted with new in vivo models expected. New partnerships have been created with multiple European industrial SMEs who wish to commercialize these technologies.
Key points of progress made
>> (WP1 - New Monomers) In the first year, 2 divinyl carbonates and 3 divinyl esters were synthesized.In the second year, synthesis of the 3 divinyl esters was scaled up to provide each in quantities of greater than 30 grams.
>> (WP2 – Characterization of monomers) The techniques of real time FTIR and photo-rheology have been succesfully coupled. The new monomers have been analyzed with the coupled techniques providing simultaneous measurement of evolution of loss and storage modulus with change in monomer conversion. Reactivity of the new monomers has been tested on homopolymers as well as in thiol-ene step growth polymerization. Additional cytotoxicity tests have been performed by I. Vakhrushev at the V.N. Orekhovich Institute of Biomedical Chemistry in Moscow using mesenchymal stem cells from human exfoliated deciduous tooth pulp. These results confirm the cytotoxicty results found in earlier studies. In vitro degradation tests with homopolymers were also carried out. Degradation was found to occur relatively slow and at a steady rate indicating the main pathway to be a desirable surface degradation.
>> (WP3 – Optimization of formulation) Mechanical testing (Dynamic Mechanical Analysis, Nanoindentation, 3-Point bending, Charpy impact tests) of the vinyl ester homopolymers and of the thiol copolymers has also been carried out. Addition of thiol leads to lower modulus and dramatically improved impact resistance. The maximum impact resistance is reached where the ratio of thiol moieties to vinyl ester moities is equal to one. Modulus can be increased by working with tetrafunctional as opposed to trifuntional thiol.
>> (WP4 – 3D Scaffolds by 3D Printing) Rectangular samples of the optimized vinyl ester-thiol copolymer for 3-point bending tests have been fabricated by stereolithography. Optimization of scaffold geometry, which was prescribed for the last six months of the project, was not completed due to the untimely death of the principal investigator.
>> (WP5 – Project Management) Project expenses and other records have been well organized throughout the course of the project. Details are to be found in the separate financial section. This final report has been prepared by S.C. Ligon and R. Liska acting on behalf of B. Husár.
Project website is available at http://www.ias.tuwien.ac.at/staff/11700521/.
In this project, new photopolymers for use as potential bone replacement materials have been developed which can be fabricated by 3D printing. Since the material itself and its degradation products should exhibit very low cytotoxicity, acrylate based reactive diluents have been replaced by a new generation of monomers with exceptionally low toxicity (vinyl carbonates and vinyl esters). Making use of the exceptional coreactivity of these vinyl monomers with alkyl thiols, polymers may be formed rapidly as is the case with analogous acrylates and yet with improved mechanical properties and significantly reduced cytotoxicity. The influence of monomer structure and thiol concentration have been investigated along with suitable fillers like hydroxyapatite. This has allowed for the development of a new class of 3D printable material with mechanical properties similar to those of natural bone. In collaboration with biologists and health care professionals, additional in vitro testing has been conducted with new in vivo models expected. New partnerships have been created with multiple European industrial SMEs who wish to commercialize these technologies.
Key points of progress made
>> (WP1 - New Monomers) In the first year, 2 divinyl carbonates and 3 divinyl esters were synthesized.In the second year, synthesis of the 3 divinyl esters was scaled up to provide each in quantities of greater than 30 grams.
>> (WP2 – Characterization of monomers) The techniques of real time FTIR and photo-rheology have been succesfully coupled. The new monomers have been analyzed with the coupled techniques providing simultaneous measurement of evolution of loss and storage modulus with change in monomer conversion. Reactivity of the new monomers has been tested on homopolymers as well as in thiol-ene step growth polymerization. Additional cytotoxicity tests have been performed by I. Vakhrushev at the V.N. Orekhovich Institute of Biomedical Chemistry in Moscow using mesenchymal stem cells from human exfoliated deciduous tooth pulp. These results confirm the cytotoxicty results found in earlier studies. In vitro degradation tests with homopolymers were also carried out. Degradation was found to occur relatively slow and at a steady rate indicating the main pathway to be a desirable surface degradation.
>> (WP3 – Optimization of formulation) Mechanical testing (Dynamic Mechanical Analysis, Nanoindentation, 3-Point bending, Charpy impact tests) of the vinyl ester homopolymers and of the thiol copolymers has also been carried out. Addition of thiol leads to lower modulus and dramatically improved impact resistance. The maximum impact resistance is reached where the ratio of thiol moieties to vinyl ester moities is equal to one. Modulus can be increased by working with tetrafunctional as opposed to trifuntional thiol.
>> (WP4 – 3D Scaffolds by 3D Printing) Rectangular samples of the optimized vinyl ester-thiol copolymer for 3-point bending tests have been fabricated by stereolithography. Optimization of scaffold geometry, which was prescribed for the last six months of the project, was not completed due to the untimely death of the principal investigator.
>> (WP5 – Project Management) Project expenses and other records have been well organized throughout the course of the project. Details are to be found in the separate financial section. This final report has been prepared by S.C. Ligon and R. Liska acting on behalf of B. Husár.
Project website is available at http://www.ias.tuwien.ac.at/staff/11700521/.