Extrusion printing of biocompatible scaffolds
Compositions and methods for making biocompatible articles are provided. A method includes preparing a 3D printable mixture and depositing successive layers of the mixture in a predetermined pattern to form a porous biocompatible article. The predetermined pattern has a porosity suitable for a bone or cartilage scaffold. Associated 3D printable compositions and porous articles made from the described methods are also described. The preparing a 3D printable mixture can comprise conjugating an alkyne-terminated polymer to a peptide to form a peptide-containing composite, or providing a mixture that comprises a ceramic material and a binder, and wherein the 3D printable mixture comprises from 50 wt. % to 80 wt. % of the ceramic material.
1 . A method of making a biocompatible article comprising:
preparing a 3D-printable mixture, wherein the preparing comprises conjugating an alkyne-terminated polymer to a peptide to form a peptide-containing composite, and wherein the peptide is a tissue-specific bioactive peptide selected from the group consisting of an osteogenic bone morphogenetic protein mimetic peptide comprising a peptide having the sequence of SEQ ID NO:1, an osteogenic glycine-histidine-lysine peptide comprising a peptide having the sequence of SEQ ID NO:2 or SEQ ID NO:4, a chondrogenic N-cadherin peptide comprising a peptide having the sequence of SEQ ID NO:3 or SEQ ID NO;5, and combinations thereof; and
depositing successive layers of the mixture in a predetermined pattern to form a porous biocompatible article,
wherein the predetermined pattern comprises a porosity suitable for a bone or cartilage scaffold.
2 . The method of claim 1 , wherein the conjugating comprises mixing the alkyne-terminated polymer, the peptide and a catalyst in an aqueous medium at a temperature of from 20 to 70° C. for a time of from 12 to 48 hours.
3 . The method of claim 1 , wherein the alkyne-terminated polymer is alkyne-terminated poly(ε-caprolactone).
4 . The method of claim 1 , wherein the alkyne-terminated polymer has a molecular weight of from 4 to 50 kDa.
5 . The method of claim 1 , wherein the catalyst is chloro(pentamethylcyclopentadienyl)(cycloocta-diene)ruthenium(II).
6 . The method of claim 1 , wherein the depositing comprises extruding the peptide-containing composite at a temperature of from 70 to 100° C.
7 . The method of claim 1 , further comprising cell seeding of the biocompatible article.
8 . The method of claim 1 , wherein the porosity is from 60 to 85%.
9 . The method of claim 1 , wherein the biocompatible article comprises an average pore size of from 300 to 600 μm.
10 . The method of claim 1 , wherein the 3D printable mixture comprises a ceramic material and a binder, and wherein the 3D printable mixture comprises from 50 wt. % to 80 wt. % of the ceramic material.
11 . The method of claim 10 , wherein the ceramic material is selected from the group consisting of hydroxyapatite, alpha-tricalcium phosphate, beta-tricalcium phosphate, and combinations thereof.
12 . The method of claim 10 , wherein the ceramic material is a powder.
13 . The method of claim 12 wherein the powder has an average particle size of from 50 nm to 50 μm.
14 . The method of claim 10 , wherein the binder comprises tetrahydrofurfuryl methacrylate, urethane dimethacrylate, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, and combinations thereof.
15 . The method of claim 10 , wherein the depositing comprises:
extruding the mixture at a temperature of from 10 to 40° C. and a pressure of from 0.3 to 5 bar to form a layer;
applying ultraviolet radiation to the layer; and
repeating the extruding and applying steps until a desired number of layers is achieved.
16 . The method of claim 10 further comprising:
sintering the article at a temperature of from 1000 to 1400° C. for 3 to 12 hours to form a sintered article.
17 . The method of claim 15 further comprising rotating the article by about 90 degrees after a predetermined number of depositing steps.
18 . The method of claim 10 , wherein the porosity is from 20 to 55%.
19 . The method of claim 10 , wherein the biocompatible article comprises an average pore size of from 600 to 1000 μm.
20 . The method of claim 1 , wherein the peptide is a tissue-specific bioactive peptide, the depositing comprises 3D-printing the successive layers of the 3D-printable mixture and the porous biocompatible article comprises a tissue-specific bioactivity suitable for a bone or cartilage scaffold.
21 . The method of claim 20 , wherein the alkyne-terminated polymer is an alkyne-terminated poly(ε-caprolactone).
22 . An article formed from the method of claim 1 .
23 . The article of claim 22 , wherein the article is selected from the group consisting of a vascularized graft, a tendon implant and a ligament implant.
24 . A biocompatible 3D printable ink composition comprising:
a biocompatible ceramic material;
a peptide-containing composite comprising a polymer and a peptide conjugated to the polymer; and
a binder;
wherein the peptide is a tissue-specific bioactive peptide selected from the group consisting of an osteogenic bone morphogenetic protein mimetic peptide comprising a peptide having the sequence of SEQ ID NO:1, an osteogenic glycine-histidine-lysine peptide comprising a peptide having the sequence of SEQ ID NO:2 or SEQ ID NO:4, a chondrogenic N-cadherin peptide comprising a peptide having the sequence of SEQ ID NO:3 or SEQ ID NO;5, and combinations thereof;
wherein the composition comprises from 50 wt. % to 80 wt. % of the ceramic material; and
wherein the ceramic material is selected from the group consisting of hydroxyapatite, alpha-tricalcium phosphate, beta-tricalcium phosphate, and combinations thereof.
25 . The composition of claim 24 , wherein the ceramic material is a powder.
26 . The composition of claim 24 , wherein the powder has an average particle size of from 50 nm to 50 μm.
27 . The composition of claim 24 , wherein the binder comprises tetrahydrofurfuryl methacrylate, urethane dimethacrylate, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, and combinations thereof.