Method comprising contacting tissue with a cross-linkable polyester prepolymer
The present inventions in various aspects provide elastic biodegradable polymers. In various embodiments, the polymers are formed by the reaction of a multifunctional alcohol or ether and a difunctional or higher order acid to form a pre-polymer, which is cross-linked to form the elastic biodegradable polymer. In preferred embodiments, the cross-linking is performed by functionalization of one or more OR groups on the pre-polymer backbone with vinyl, followed by photopolymerization to form the elastic biodegradable polymer composition or material. Preferably, acrylate is used to add one or more vinyls to the backbone of the pre-polymer to form an acrylated pre-polymer. In various embodiments, acrylated pre-polymers are co-polymerized with one or more acrylated co-polymers.
1. A method for forming a biodegradable elastomeric material, comprising the steps of:
(a) reacting a first component comprising two or more functionalities of the general formula —OR, where R of each group is independently hydrogen or alkyl, with a second component comprising two or more acid ester functionalities to form a mixture of pre-polymers having a molecular weight in the range between about 300 Da and about 75,000 Da;
(b) reacting the mixture of pre-polymers with an acrylate to form a mixture of acrylated pre-polymers; and
(c) irradiating the acrylated pre-polymer mixture to cross-link at least a portion of the acrylated pre-polymers and form a biodegradable elastomeric material; wherein the pre-polymer mixture is not heated above about 45° C. during irradiation.
2. The method of claim 1 , wherein the acrylate is a methacrylate or a vinyl methacrylate.
3. The method of claim 1 , wherein the acrylate has a structure as follows:
wherein, R 1 represents methyl or hydrogen;
R 2 , R 2 ′, and R 2 ″ represent independently alkyl, aryl, heterocycles, cycloalkyl, aromatic heterocycles, multicycloalkyl, hydroxyl, ester, ether, halide, carboxylic acid, amino, alkylamino, dialkylamino, trialkylamino, amido, carbamoyl thioether, thiol, alkoxy, or ureido groups, and branched and substituted versions thereof.
4. The method of claim 1 , wherein the acrylate has a structure as follows:
5. The method of claim 1 , wherein the pre-polymer mixture is not heated above about 25° C. during irradiation.
6. The method of claim 1 , wherein step (b) comprises adding to the reaction one or more of an acrylated dextran, acrylated hyaluronic acid, acrylated chitosan, and acrylated poly(ethylene glycol).
7. The method of claim 1 , wherein the second component is a substituted or unsubstituted dioic acid ester.
8. The method of claim 1 , wherein the second component comprises an amino ester functionality and the biodegradable elastomeric material comprises a poly-β-amino ester polymer.
9. The method of claim 1 , wherein, in step (c) the mixture comprises a photoinitiator.
10. The method of claim 9 , wherein the photoinitiator is selected from the group consisting of 2-dimethoxy-2-phenyl-acetophenone, 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone, 1-hydroxycyclohexyl-1-phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2-benzyl-2-(dimehylamino)-1-[4-morpholinyl) phenyl]-1-butanone, methylbenzoylformate, oxy-phenyl-acetic acid-2-[2-oxo-2-phenyl-acetoxy-ethoxy]-ethyl ester, 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone, diphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide, phosphine oxide, phenyl bis(2,4,6-trimethyl benzoyl), and combinations thereof.