Biocompatible materials

Abstract

A resin composition, the resin composition comprising a prepolymer (209) and optionally one or more diluent(s) (FIG. 3A), the prepolymer (209) comprising repeating units having at least one carbonate linkage and at least one unsaturated side-chain, the at least one optional diluent(s) comprising at least one unsaturated side-chain, wherein either or both of the prepolymer (209) and the at least one optional diluent(s) comprises at least one O═C—N linkage, preferably a urethane linkage.

Claims

1. A resin composition, the resin composition comprising a prepolymer and at least one diluent, the prepolymer comprising repeating units having at least one carbonate linkage and at least one unsaturated side-chain, said at least one diluent(s) comprising at least one unsaturated side chain, wherein either the prepolymer comprises at least one O═C—N linkage or said at least one diluent comprises at least one O═C—N linkage but not both the prepolymer and said at least one diluent comprises at least one O═C—N linkage.

2. A resin composition according to claim 1, wherein the prepolymer comprises at least one O═C—N linkage.

3. A resin composition according to claim 1, wherein the at least one O═C—N linkage is a urethane linkage.

4. A resin composition according to claim 1, the prepolymer comprising repeating units having at least one carbonate linkage, at least one urethane linkage, and at least one unsaturated side-chain.

5. A resin composition according to claim 2, further comprising a cross-linker, the cross-linker comprising a moiety that is capable of reacting with the at least one unsaturated side-chain of the prepolymer and/or the at least one diluent.

6. A resin composition according to claim 5, wherein the cross-linker has the formula (vi): ##STR00008##

7. A resin composition according to claim 2, wherein the at least one diluent comprises plural unsaturated side-chains.

8. A resin composition according to claim 2, wherein the at least one diluent is selected from the following (ii) to (v): ##STR00009##

9. A resin composition according to claim 1, wherein the prepolymer has the formula (vii): ##STR00010## wherein R group is an aliphatic or an aromatic moiety, R.sup.1 is an aliphatic or an aromatic moiety, R.sup.2 is an aliphatic or an aromatic moiety, R.sup.3 is an aliphatic or an aromatic moiety, and R.sup.4 is an aliphatic or an aromatic moiety, and wherein x is a number that is less than one hundred.

10. A resin composition, the resin composition comprising a prepolymer, the prepolymer comprising repeating units having at least one carbonate linkage and at least one unsaturated side-chain, wherein the prepolymer comprises at least one O═C—N linkage and has the formula (viii): ##STR00011## wherein R group is an aliphatic or an aromatic moiety, R.sup.1 is an aliphatic or an aromatic moiety, R.sup.2 is an aliphatic or an aromatic moiety, R.sup.3 is an aliphatic or an aromatic moiety, and R.sup.4 is an aliphatic or an aromatic moiety, and wherein x is a number that is less than one hundred.

11. A resin composition according to claim 1, wherein the prepolymer is fabricated from components comprising the formulae (ix): ##STR00012## wherein R group is an aliphatic or an aromatic moiety, R.sup.1 is an aliphatic or an aromatic moiety, R.sup.2 is an aliphatic or an aromatic moiety, R.sup.3 is an aliphatic or an aromatic moiety, and R.sup.4 is an aliphatic or an aromatic moiety, and wherein x is a number that is less than one hundred.

12. A resin composition according to claim 5, wherein the prepolymer is present in a quantity of between 10 and 100 w/w % of the total composition, the diluent is present in a quantity of between 0 and 50 w/w % of the total composition, and the cross-linker is present in a quantity of between 0 and 50 w/w % of the total composition.

13. A cross-linked polymer comprising a resin composition of claim 1 which has been cross linked.

14. A method of fabricating a cross-linked polymer, the method comprising: i. providing a resin composition according to claim 1.

15. A method according to claim 14, comprising: ii. contacting the resin composition with a initiator; and iii. providing an energy source to activate the initiator.

16. A method according to claim 15, comprising contacting the resin composition with a photoinitiator and exposing the resin composition to a light source, for example, UV light.

17. A method according to claim 15, wherein the initiator is present in a quantity of between 0 and 5 w/w% of the total composition.

18. A method according claim 15, comprising forming the cross-linked polymer by stereolithography.

19. A method according to claim 15, the method further comprising step iv. providing a reagent for halogenation of the at least one unsaturated side chain.

20. A method according to claim 15, further comprising a further step selected from one or more of the following group: step v. providing a reagent for alkylation of the at least one unsaturated side chain; step vi. providing a reagent for functionalising the at least one unsaturated side chain with a hydrophobic moiety; step vii. providing a reagent for functionalising the at least one unsaturated side chain with a cell adhesion moiety.

21. A resin composition according to claim 1, wherein said at least one diluent comprises at least one O═C—N linkage.

22. A resin composition, the resin composition comprising a prepolymer and at least one diluent, said at least one diluent(s) comprising at least one unsaturated side chain and at least one O═C—N linkage, the prepolymer comprising repeating units having at least one carbonate linkage and at least one unsaturated side-chain, wherein the prepolymer is fabricated by polymerisation of monomer 202; ##STR00013## and wherein the prepolymer comprises the repeating unit shown in formula; ##STR00014##

Description

(1) Embodiments of the invention will now be described by way of example only with reference to the accompanying drawings in which:

(2) FIG. 1 is a synthetic route to a prepolymer of the prior art for use in a resin composition for the fabrication of a polycarbonate cross-linked polymer;

(3) FIG. 2A is a synthetic route to a prepolymer for use in a resin composition for use in forming a cross-linked polymer, according to embodiments of the invention;

(4) FIG. 2B is the .sup.1H NMR spectrum of the first cyclic carbonate 202;

(5) FIG. 2C is the .sup.1H NMR spectrum of the second cyclic carbonate 206;

(6) FIG. 2D is the .sup.1H NMR spectrum the .sup.13C NMR spectrum of the polycarbonate prepolymer 604, which was synthesised via polymerisation of the first cyclic carbonate monomer 202;

(7) FIG. 3A is a selection of different types of diluent for use in the resin composition according to embodiments of the invention;

(8) FIG. 3B is the .sup.1H NMR spectrum and the .sup.13C NMR spectrum of the diluent 303;

(9) FIG. 4 is a cross-linker for use in the resin composition according to embodiments of the invention;

(10) FIG. 5 shows a series of schematic reaction mechanisms that may be used to cross-link the pre-polymer with the cross-linker, according to some embodiments of the invention;

(11) FIG. 6 shows a graph of the distribution of molecular weights of prepolymers for use in resin compositions according to embodiments of the invention;

(12) FIG. 7 is a graph showing the glass transition temperatures (T.sub.g) of the cross-linked polymers, according to some embodiments of the invention;

(13) FIG. 8A is a graph showing the curing kinetics of components of resin compositions;

(14) FIG. 8B is a graph showing the viscosity of the resin composition when using different concentrations of diluent, according to some embodiments of the invention;

(15) FIG. 8C is a graph showing the viscosity of the resin composition versus time, when using different concentrations of photoinitiator, according to some embodiments of the invention;

(16) FIG. 8D is a graph showing the viscosity of the resin composition versus concentration of photoinitiator, according to some embodiments of the invention;

(17) FIG. 9 is a device comprising a cross-linked polymer with shape memory properties, according to embodiments of the invention;

(18) FIG. 10A is a schematic reaction showing iodination post-polymerisation functionalisation of the cross-linked polymer, according to embodiments of the invention;

(19) FIG. 10B is a graph comparing the x-ray density of non-iodinated and iodinated cross-linked polymer, according to embodiments of the invention;

(20) FIG. 11A is a schematic reaction showing alkylation post-polymerisation functionalisation of the cross-linked polymer, according to embodiments of the invention;

(21) FIG. 11B is a photograph of a comparison of two cross-linked polymers showing the effect of alkylation post-polymerisation functionalisation to increase the hydrophobicity, according to an embodiment of the invention;

(22) FIG. 12A is computed tomography (CT) reconstruction of a 3D printed cross-linked polymer according to an embodiment of the invention, and a comparative example showing the porosity of a gas blown foam;

(23) FIG. 12B is a graph showing the porosity and surface area versus the pore size of a 3D printed cross-linked polymer, according to an embodiment of the invention;

(24) FIG. 13 is an experimental set-up and a graph showing the compressive mechanical properties of a 3D printed cross-linked polymer, according to an embodiment of the invention;

(25) FIG. 14 is an experimental set-up and a graph showing analysis of the shape memory behaviour of a 3D printed cross-linked polymer, according to an embodiment of the invention;

(26) FIG. 15 is a series of photographs showing the shape recovery of a model SMP over the course of 9 minutes, according to an embodiment of the invention;

(27) FIG. 16A is a graph showing the degradation of a series of cross-linked polymers, according to some embodiments of the invention;

(28) FIG. 16B is a graph showing the degradation of a cross-linked polymer, according to some embodiments of the invention;

(29) FIG. 16C is a graph showing the storage modulus versus time of a series of cross-linked polymers, according to some embodiments of the invention;

(30) FIG. 17A is graph showing the cytocompatibility testing using pre-osteoblasts of the cross-linked polymer, according to some embodiments of the invention;

(31) FIG. 17B is a selection of images showing the spread of cells across the cross-linked polymer, according to some embodiments of the invention.

(32) Referring first to FIG. 1, there is shown a synthetic route 1 to a prepolymer 102 of the prior art for use in a resin composition (I A Barker et. al., Biomaterials Science, 2014, 2, 472-475). The prepolymer 102 is an oligomer of a linear polycarbonate homopolymer comprising carbonate monomers 101. Polymerisation of the carbonate monomer 101 was achieved in an organocatalyzed reaction using a DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) initiator 103 in water. The prepolymer 102 was formulated into a resin composition (not shown) further comprising a photoinitiator (not shown) and a thiol crosslinker (not shown). The prepolymer 102 of the resin composition underwent cross-linking to fabricate a polycarbonate cross-linked polymer (not shown) in a microstereolithographic process. The polycarbonate cross-linked polymer was degradable, and was suitable for use as a tissue scaffold. However, the polycarbonate cross-linked polymer did not exhibit shape memory properties.

(33) Referring now to FIG. 2A, there is shown a synthetic route 2 to a prepolymer 209 for use in a resin composition, according to an embodiment of the invention. In this embodiment, the prepolymer 209 was fabricated in chain extension reaction (e) from a polycarbonate oligomer 207 and a diisocyanate 208 to produce the prepolymer 209, which is a mixed polycarbonate polyurethane oligomer. In this embodiment, the diisocyanate 208 is isophorone diisocyanate (IPDI) 208. The prepolymer 209 had molecular weights of less than or equal to 3 kDa and polydispersity indices (PDI) of 1.4.

(34) The polycarbonate 207 was synthesised in ring opening polymerisation reaction (d) from first cyclic carbonate 202 and second cyclic carbonate 206 in the presence of water and a DBU initiator 103. The reaction (d) of first cyclic carbonate 202 and second cyclic carbonate 206 yielded oligomers of polycarbonate 207 with lengths of below 1.2 kDa with PDIs of below 1.2.

(35) In this embodiment, first cyclic carbonate 202 is 5-[(allyloxy)methyl]-5-ethyl-1,3-dioxan-2-one, and second cyclic carbonate 206 is 9-(5-norbornen-2-yl)-2,4,8,10-tetraoxa-3-spiro[5.5]undecanone, which were synthesised in accordance with the protocols described in IA Barker et. al., Biomaterials Science, 2014, 2, 472-475; and also in Y He et. al., Reactive and Functional Polymers, Vol. 71, Issue 2, February 2011, p. 175-186.

(36) First cyclic carbonate 202 was synthesised in one step, in reaction (a) from diol 201 and propionyl chloride in the presence of triethylamine at 0° C. In this embodiment, diol 201 is 2-[(allyloxy)methyl]-2-ethyl-1,3-propanediol.

(37) Second cyclic carbonate 206 was synthesised in two steps, using polyol 203 as the starting material. In reaction (b), polyol 203 and aldehyde 204 underwent reaction in the presence of hydrochloric acid to produce diol 205. Diol 205 underwent subsequent reaction, in reaction (c), with propionyl chloride in the presence of triethylamine at 0° C. to produce the second carbonate 206. In this embodiment, polyol 203 is pentaerythritol, aldehyde 204 is bicyclo[2.2.1]hept-5-ene-2-carboxaldehyde, and diol 205 is [5-(hydroxymethyl)-2-(5-norbornen-2-yl)-1,3-dioxan-5-yl]methanol.

(38) Referring also to FIG. 2B and FIG. 2C, there is shown the .sup.1H NMR spectrum of the first cyclic carbonate 202 (FIG. 2B), and the .sup.1H NMR spectrum of the second cyclic carbonate 206 (FIG. 2C).

(39) In alternative embodiments, a prepolymer (prepolymer 604, not shown) may be fabricated by polymerisation the first cyclic carbonate 202 only. The .sup.1H NMR spectrum the .sup.13C NMR spectrum for this prepolymer is shown in FIG. 2D.

(40) In alternative embodiments, a prepolymer (not shown) may be fabricated by polymerisation of the second cyclic carbonate 206 only.

(41) In embodiments, polycarbonate 207 may be used as a prepolymer in a resin composition according to the invention.

(42) The prepolymers for use in the resin compositions of the invention may comprise only carbonate linkages, for example, those prepolymers fabricated from either first cyclic carbonate 202 or second cyclic carbonate 206 only. Alternatively, the polycarbonate prepolymers may be further reacted in a chain extension reaction using a diisocyanate (e.g. diisocyanate 208) to produce alternative prepolymers comprising one or more urethane linkages.

(43) Referring now to FIG. 3A, there is shown different types of diluent 3, according to embodiments of the invention. There is shown a first diluent 301, a second diluent 302, a third diluent 303, and a fourth diluent 304. The first diluent 301 is 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione, the second diluent 302 is 6-(allyloxycarbonylamino)hexylamino 3-butenoate, the third diluent 303 is 3-[(allyloxycarbonylamino)methyl]-3,5,5-trimethylcyclohexylamino 3-butenoate, and the fourth diluent 304 is diallyl phthalate.

(44) Referring also to FIG. 3B, there is shown the .sup.1H NMR spectrum and the .sup.13C NMR spectrum of the diluent 303.

(45) Each of the first, second, third, and fourth diluent 301, 302, 303 and 304 comprise two or more unsaturated side-chains. In this embodiment, in each case the unsaturated side-chains comprise an alkene moiety.

(46) Referring now to FIG. 4, there is shown a cross-linker 4 according to an embodiment of the invention. In this embodiment, the cross-linker 401 is pentaerythritol tetrakis(3-mercaptopropionate). The thiol moieties of the cross-linker 401 are capable of reacting with unsaturated moieites, specifically unsaturated side-chains of the prepolymer 209 and of the first, second, third, and fourth diluent 301, 302, 303, and/or 304.

(47) In embodiments, the prepolymer 209 is combined with the cross-linker 401, and one or more of the first, second, third, and fourth diluent 301, 302, 303 and/or 304, to produce a range of resin compositions.

(48) In alternative embodiments, a prepolymer (not shown) may be fabricated from the first cyclic carbonate 202 only. In alternative embodiments, a prepolymer (not shown) may be fabricated from the second cyclic carbonate 206 only. In embodiments, the prepolymer (not shown) may comprise a copolymer of the first cyclic carbonate 202 and the second cyclic carbonate 206. These may or may not be chain extended using a diisocyanate (e.g. diisocyanate 208).

(49) One or more of the prepolymers described may be combined with the cross-linker 401, and one or more of the first, second, third, and fourth diluent 301, 302, 303 and/or 304, to produce a range of resin compositions according to the invention, for fabrication into cross-linked polymers according to the invention.

(50) The components of the resin compositions, i.e. the prepolymer, the diluents, and/or the cross-linker, for fabricating the cross-linked polymers of the invention may be added in different amounts to tune or vary the properties, e.g. degradability, shape memory properties, of the resulting cross-linked polymer. In embodiments wherein the prepolymer comprises a urethane linkage, the quantity of the diluent in the resin composition may be 0 wt. %. In this case, the prepolymer may be capable of directly cross-linking to moieties on or within the prepolymer itself and/or to a cross-linker.

(51) Advantageously, the type of prepolymer and/or reactive diluent and/or cross-linker that is added to the resin composition to fabricate the cross-linked polymers of the invention may be varied to tune the properties of the cross-linked polymer. For example, the structure of the prepolymer may be varied by using different types and/or concentrations of monomer to fabricate the prepolymer. In embodiments, the prepolymer is fabricated from one type of carbonate monomer. In other embodiments, the prepolymer is fabricated from more than one type of carbonate monomer. The concentration of each monomer in the prepolymer may be adjusted or varied to tune the properties of the resulting cross-linked polymer. In embodiments, the prepolymer may be chain extended using an isocyanate to provide a urethane linkage in the prepolymer. The type of isocyanate in the prepolymer may be varied to tune the properties of the resulting cross-linked polymer that is fabricated from a resin composition containing the prepolymer.

(52) The cross-linked polymer of the invention comprises one or more urethane and/or urea linkage. The origin of the urethane linkage is from one or more of a urethane linkage in the prepolymer and/or one or more diluents 302 and/or 303. For example, the prepolymer need not comprise a urethane linkage, e.g. the prepolymer may be a polycarbonate that consists of carbonate linkages only. In this case, the origin of the urethane and/or urea linkage(s) is from the diluents 302 and/or 303 only.

(53) Alternatively, the prepolymer for use in the resin compositions of the invention may comprise carbonate linkages in addition to one or more urethane linkages. In this case, the origin of the urethane and/or urea linkage(s) is from the prepolymer (e.g. prepolymer 209) and may also be (but need not be) from the diluents 302 and/or 303.

(54) The resin compositions were combined with a photoinitiator and were printed using a microstereolithographic apparatus to produce cross-linked polymers.

(55) Referring now to FIG. 5, there is shown a series of schematic reaction mechanisms 5 that may be used to cross-link the prepolymer, e.g. 209, with the cross-linker, e.g. 401, according to embodiments of the invention. There is shown a radical alkene mechanism 5A, a radical alkyne mechanism 5B, a nucleophilic alkene mechanism 5C, and a nucleophilic alkyne mechanism 5D.

(56) In embodiments, the cross-linker, e.g. cross-linker 401, comprises multiple thiol moieties. The thiol moieties of the cross-linker, e.g. cross-linker 401, may react with the unsaturated side-chains of the prepolymer, e.g. 209, and/or the diluent(s) 301, 302, 303, and/or 304. Wherein the unsaturated side-chains comprise an alkene moiety, and the resin composition is combined with a radical initiator, e.g. a photoinitiator, then the cross-linking reaction between oligomer chains of the prepolymer, e.g. 209 and the cross-linker, e.g. 401, and/or the diluents, e.g. 301, 302, 303 and/or 304, may proceed via the radical alkene mechanism 5A.

(57) Wherein the unsaturated side-chains comprise an alkyne moiety, and the resin composition is combined with a radical initiator, e.g. a photoinitiator, then the cross-linking reaction between oligomer chains of the prepolymer, e.g. 209 and the cross-linker, e.g. 401, and/or the diluents, e.g. 301, 302, 303 and/or 304, may proceed via the radical alkene mechanism 5B.

(58) In contrast, the unsaturated side-chains of a prepolymer and/or a or the diluent(s) may comprise an alkene moiety comprising an electron withdrawing group, which may undergo a nucleophilic addition reaction with the cross-linker, for example, a nucleophilic addition of a thiol moiety of a cross-linker, e.g. cross-linker 401, in nucleophilic alkene mechanism 5C.

(59) Alternatively, unsaturated side-chains of a prepolymer and/or a or the diluent(s) may comprise an alkyne moiety comprising an electron withdrawing group, which may undergo a nucleophilic addition reaction with the cross-linker, for example, a nucleophilic addition of a thiol moiety of a cross-linker, e.g. cross-linker 401, in nucleophilic alkyne mechanism 5D.

(60) The cross-linking processes described above may be performed on an apparatus for microstereolithography (not shown), which 3D prints each layer of the cross-linked polymer, by providing a initiator, e.g. a photoinitiator and a light source, to cure the cross-linked polymer.

(61) Advantageously, the quantity of prepolymer and/or diluent and/or and/or cross-linker may be altered to afford a range of cross-linked polymer with different properties, e.g. mechanical properties, glass transition temperatures (T.sub.g), degradability, and so on. In this way, the properties of the cross-linked polymer of the present invention may be tuned depending on the application. The type of diluent(s) may also be varied to afford cross-linked polymers with different properties.

(62) Referring now to FIG. 6, there is shown a graph 6 showing the distribution of molecular weights of prepolymers that may be used in resin compositions to fabricate cross-linked polymers according to embodiments of the invention. There is shown the distribution of molecular weights for prepolymers 601, 602, 603, and 604.

(63) The prepolymer 601 was fabricated via chain extension of an oligomer fabricated from first cyclic carbonate 202 (shown in FIG. 2A) with isophorone diisocyanate 208 (shown in FIG. 2A).

(64) The prepolymer 602 is the prepolymer 209 (shown in FIG. 2A).

(65) Prepolymer 603 is a polycarbonate prepolymer comprising an alternating copolymer of first cyclic carbonate 202 and second cyclic carbonate 206, which underwent iodination. No urethane linkages are present in prepolymer 603.

(66) Prepolymer 604 is a polycarbonate prepolymer was fabricated from a homopolymer of first cyclic carbonate 202. No urethane linkages are present in prepolymer 604.

(67) The molecular weights (M.sub.n) of the prepolymers 601 and 602 are higher than those of the prepolymers 603 and 604. This is because the chains of the prepolymers 601 and 602 have been chain extended using the diisocyanate 208, whereas the cross-linked polymers 603 and 604 are polycarbonates only, and did not undergo chain extension to produce a urethane linkage.

(68) Referring now to FIG. 7, there is shown a graph 7 showing the glass transition temperatures (T.sub.g) of the cross-linked polymers, according to embodiments of the invention. The glass transition temperature (T.sub.g) is shown for the cross-linked polymers 701, 702, 703, 704, 705, and 706.

(69) The cross-linked polymers 701, 702, 703, 704, and 705 were fabricated from a resin composition comprising a prepolymer, the prepolymer being fabricated via chain extension of prepolymer 604 with hexamethylene diisocyanate (HDI). The cross-linked polymers 701, 702, 703, 704, and 705 were fabricated in the absence of diluents.

(70) The cross-linked polymer 706 was fabricated from a resin composition comprising a prepolymer (not shown), the prepolymer being fabricated via chain extension of an oligomer consisting of the second cyclic carbonate 206 reacted with isophorone diisocyanate 208. The cross-linked polymer 706 was fabricated from a resin composition comprising the first diluent 301 and the third diluent 303 (shown in FIG. 3A).

(71) The glass transition temperature (T.sub.g) of the cross-linked polymers 701, 702, 703, 704, and 705 ranged from below 0° C. to above nearly 45° C. In contrast, the cross-linked polymer 706 had a glass transition temperature (T.sub.g) of 86.6° C. Without wishing to be bound any by theory, it is thought that this is a result of the flexible carbonate linkages and plasticising side groups, i.e. the allyl side-chains, in the cross-linked polymers 701, 702, 703, 704, and 705, which comprises the first cyclic carbonate 202. These structural features act to lower the glass transition temperature (T.sub.g).

(72) In contrast, the cross-linked polymer 706 exhibited the highest glass transition temperature (T.sub.g). Without wishing to be bound by any theory, it is thought that provision of first diluent 301 and third diluent 303 (shown in FIG. 3A) in the resin composition used to fabricate cross-linked polymer 706, provide greater steric hindrance, in addition to the more ‘rigid’ second cyclic carbonate 206, both effects of which contribute to increase the glass transition temperature (T.sub.g).

(73) Therefore, the cross-linked polymers of the present invention may be tuned to exhibit different glass transition temperature (T.sub.g) by addition of different types and quantities of diluent.

(74) Referring now to FIG. 8A, there is shown a graph 8A showing the curing kinetics of components of the resin composition of the invention. There is shown the curing kinetics for the reactions 801, 802, 803, 804, and 805.

(75) Reaction 801 comprised the cross-linker 401 and the diluent 304. The ene:thiol ratio was 1:1 with 0.1 wt. % initiator.

(76) Reaction 802 comprised the prepolymer 102 shown in FIG. 1 and the cross-linker 401. The ene:thiol ratio was 1:1 with 0.1 wt. % initiator.

(77) Reaction 803 comprised the cross-linker 401 and the diluent 303. The ene:thiol ratio was 1:1 with 0.1 wt. % initiator.

(78) Reaction 804 comprised the prepolymer 207 and the cross-linker 401. The ene:thiol ratio was 1:1 with 0.1 wt. % initiator.

(79) Reaction 805 comprised the cross-linked 401 and the diluent 301. The ene:thiol ratio was 1:1 with 0.1 wt. % initiator.

(80) In these reactions, stoichiometric amounts of alkenes with the cross-linker 401 (20 mg) were added to 600 microlitres of CDCl.sub.3 with 1% (wt) Irgacure 814 and added to NMR tubes. The samples were cured at 405 nm.

(81) The highest conversion was observed for reaction 805. The curing kinetics shown for reaction 805 in graph 8A indicate that the diluent 301 is most reactive with the cross-linker 401.

(82) The lowest conversion was observed in the reaction 801. This shows that the diluent 304 may be used to decrease the conversion or as a method for spatial temporal control.

(83) Referring now to FIG. 8B, there is shown a graph 8B showing the viscosity of the resin composition when using different concentrations of diluent, according to some embodiments of the invention. The inclusion of solvent was utilized to reduce resin viscosity and achieve higher print resolution, with greater than 40% wt appearing to result in both diminishing returns and reduced print viability due to both shrinkage and mechanical failure. Photoinitiator concentration of less than 0.5% wt was found to provide rapid curing of the polymer system, as determined through rheological testing.

(84) Referring now to FIG. 8C, there is shown a graph 8C of the viscosity of the resin composition versus time, when using different concentrations of photoinitiator, according to some embodiments of the invention. Referring also to FIG. 8D, there is shown a graph 8D of the viscosity of the resin composition versus concentration of photoinitiator, according to some embodiments of the invention. A photoinitiator concentration of less than 0.5 wt. % was shown to provide rapid curing of the polymer system, as determined through rheological testing. The viscosity of the resin composition increased as the concentration of the photoinitiator was increased within the resin composition.

(85) Advantageously, the resin compositions of the present invention exhibit viscosities that are highly processable in additive manufacturing techniques, for example, on stereolithographic apparatus. This enables the resin compositions of the present invention to be used to fabricate devices with highly complex microarchitectures, such devices with as uniform porosity.

(86) Referring now to FIG. 9, there is shown a device 9 comprising a cross-linked polymer with shape memory properties, according to embodiments of the invention. The device 9 was printed using a microstereolithographic process. The resin composition was contacted with a photoinitiator, and the microstereolithography apparatus provided the UV light necessary to cure the resin composition into a cross-linked polymer of device 9. The device 9 is porous, and may be used as tissue scaffold, for example.

(87) Advantageously, when the resin compositions were printed using microstereolithography, no photoinhibitor was needed to achieve the desired resolution, and print times were averaged at 10 to 30 seconds per slice, with more porous, i.e. smaller struts and lower porosity, materials required longer exposure times.

(88) The device 9 was printed with a range of pore sizes ranging from 200 μm to 1500 μm. Advantageously, this has been shown to provide an ideal pore size range for a range of biomedical applications, e.g. wherein the device 9 is a tissue scaffold, for cell growth. Porosities ranging from 0.7 to 0.95 were achievable based on 10.3 tessellation geometry.

(89) Advantageously, using a microstereolithographic process with the resin compositions of the present invention, the design of the device 9 may be manipulated to provide different surface area, pore interconnectivity, specific morphology. More advantageously, the intricacy of the design of the device 9 is not limited or constrained by the processability of the resin composition, or the mechanical properties of the resulting cross-linked polymer. The design manipulation of device 9 for fabrication using a microstereolithographic process may be achieved using image manipulation and freeware design software. Advantageously, this method of fabricating device 9 was reproducible using resin compositions, e.g. cross-linked polymers fabricated from prepolymers and cross-linker 401 in a ratio of 1:1 ene to thiol, the prepolymers fabricated from first cyclic carbonate 202, wherein the only variable was the exposure time of the UV light to the resin composition to cure the cross-linked polymer.

(90) Referring now to FIG. 10A, there is shown a schematic reaction 10A of iodination post-polymerisation functionalisation of the cross-linked polymer 1000, according to embodiments of the invention. In the schematic reaction 10A, there is shown the cross-linked polymer 1000, and an iodinated cross-linked polymer 1001. The cross-linked polymer 1000 comprises a functional group FG, which in this embodiment is an alkene side-chain. Post-polymerisation, i.e. after the resin composition comprising prepolymer 209 was fabricated into the cross-linked polymer 1000 using the stereolithography apparatus, the cross-linked polymer 1000 underwent reaction with iodine, I.sub.2, across the functional group FG to produce the iodinated cross-linked polymer 1001.

(91) Referring also to FIG. 10B, there is shown a graph 10B comparing the x-ray density of the cross-linked polymer 1000 and the functionalised cross-linked polymer 1001, according to embodiments of the invention. The graph 10B shows that the iodinated cross-linked polymer 1001 exhibits a greater x-ray density in comparison with the non-iodinated cross-linked polymer 1000. Therefore, the iodinated cross-linked polymer 1001 is visible under clinical imaging such as angiography. This is advantageous for applications wherein the iodinated cross-linked polymer 1001 is a tissue scaffold so that the device, e.g. device 9, can be located within the patient, for example, to determine the degradation rate of the iodinated cross-linked polymer 9 within the device 9.

(92) In addition, the iodinated cross-linked polymer 1001 has the following properties in comparison with the non-iodinated cross-linked polymer 1000: (i) the polymer density is increased; (ii) the iodinated cross-linked polymer 1001 is more mechanically stable in comparison with the non-iodinated cross-linked polymer 1000; (iii) reduced rates of mass loss and swelling are observed in comparison with the non-iodinated cross-linked polymer 1000.

(93) Referring now to FIG. 11A, there is shown is a schematic reaction 11A showing alkylation post-polymerisation functionalisation of the cross-linked polymer 1000, according to embodiments of the invention. In the schematic reaction 11A, there is shown the cross-linked polymer 1000, and an alkylated cross-linked polymer 1002. The cross-linked polymer 1000 comprises a functional group FG, which in this embodiment is an alkene side-chain. Post-polymerisation, i.e. after the resin composition 209 was printed into the cross-linked polymer 1000 using the stereolithography apparatus, the cross-linked polymer 1000 underwent reaction with dodecane thiol RSH, across the functional group FG to produce the alkylated cross-linked polymer 1002. This reaction occurred across the surface of the cross-linked polymer 1000.

(94) Referring also to FIG. 11B, there is shown a photograph 11B of a comparison the cross-linked polymer 1000 and the alkylated cross-linked polymer 1002, illustrating the increase in the hydrophobicity upon alkylation, according to an embodiment of the invention. There is shown the cross-linked polymer 1000, which was not alkylated or modified post-polymerisation, and the alkylated cross-linked polymer 1002. The cross-linked polymer 1000 and the alkylated cross-linked polymer 1002 were soaked in water, removed, and the strain recovery was monitored over a period of ten minutes to produce cross-linked polymer after ten minutes 1000T and alkylated cross-linked polymer after ten minutes 1002T. The photograph 11B shows that the rate of strain recovery in the alkylated cross-linked polymer after ten minutes 1002T was slowed in comparison with the rate of strain recovery in the cross-linked polymer after ten minutes 1000T.

(95) The introduction of an alkyl chain moiety to produce the alkylated cross-linked polymer 1002, e.g. a dodecane alkyl chain moieties, had the following effects in comparison to the cross-linked polymer 1000: (i) the glass transition temperature (T.sub.g) did not change upon alkylation, i.e. the glass transition temperature (T.sub.g) of the cross-linked polymer 1000 is substantially the same as that of the alkylated cross-linked polymer 1002; (ii) the hydrophobicity increased, i.e. the influx of water was altered. Therefore, the rate of strain recovery, shape memory, volume recovery, and/or shape recovery of the cross-linked polymer may be tuned with alkylation.

(96) Advantageously, the functionalisation of the unsaturated side-chain of the cross-linked polymer, e.g. cross-linked polymer 1000, allows for further functionality to be introduced to the cross-linked polymer that may not be otherwise compatible with stereolithography, or other 3D printing techniques. Moreover, the functionalisation of the cross-linked polymer 1000 is not limited to iodination or alkylation. Other functionalisation may be performed on the unsaturated side-chain, e.g. addition of bromine to an alkene moiety, click chemistry of an azide to an alkyne moiety, and any other functionalisation of an unsaturated side-chain.

(97) Referring now to FIG. 12A, there is shown two computed tomography (CT) images 12A; a reconstruction of a 3D printed cross-linked polymer 12A1 according to an embodiment of the invention, and an example showing the porosity of a gas blown foam polymer 12A2. Both the 3D printed polymer and the gas blown foam polymer were fabricated from an identical resin composition comprising a polycarbonate prepolymer, which was chain extended using IPDI, cross-linked with cross-linker 401, using propylene carbonate was used as a diluent. Referring also to FIG. 12B, there is shown a graph of the porosity (%), P, and also the surface area (cm.sup.−1), SA, versus the pore size of the 3D printed cross-linked polymer 12A1 of FIG. 12A. The 3D printed cross-linked polymer 12A1 was printed using a microstereolithography process, which allows for a specific and ordered pore morphology to be controlled during the design and fabrication. In contrast, the example showing the porosity of a gas blow foam polymer 12A2, shows irregular pore morphology. The gas blown foam polymer 12A2 comprises a cross-linked polymer that is low density, has good shape memory performance, and has good biocompatibility. However, the morphological disparity throughout a single foam sample introduces numerous problems for long term usage in biomedical applications.

(98) Advantageously, the cross-linked polymers of the present invention, comprise high porosity, high surface area, regular geometries and controlled physical attributes, which allow for their use in a wide range of applications, particularly medical applications.

(99) Referring now to FIG. 13, there is shown an experimental set-up 13A and a graph 13B showing the compressive mechanical properties of a 3D printed cross-linked polymer, according to an embodiment of the invention. In the experimental set-up 13A, there is shown a cross-linked polymer sample 1301 and a rig 1302 for applying stress to measure the compressive strain (%) of the cross-linked polymer sample 1301. In the graph 13B, there is shown the compressive strain (%) plotted against the stress (MPa) for a series of examples of the cross-linked polymer sample 1301, cross-linked polymers 1301A, 1301B, 1301C, 1301D, and 1301E. The cross-linked polymers 1301A, 1301B, 1301C, 1301D, and 1301E were tested wet at 37° C.

(100) Cross-linked polymer 1301A was fabricated from the prepolymer 207.

(101) Cross-linked polymer 1301B was fabricated from the prepolymer 209.

(102) Cross-linked polymer 1301C was fabricated from the prepolymer 209.

(103) Cross-linked polymer 1301D was fabricated from a prepolymer (not shown), the prepolymer comprising the prepolymer 102 and isophorone diisocyanate 208.

(104) Cross-linked polymer 1301E was fabricated from a prepolymer (not shown), the prepolymer comprising the prepolymer 102 and hexamethylene diisocyanate.

(105) Referring now to FIG. 14, there is shown an experimental rig 14A and a graph 14B showing analysis of the shape memory behaviour of a 3D printed cross-linked polymer, according to an embodiment of the invention. In the experimental set-up 14A, there is shown a cross-linked polymer sample 1401 and a rig 1402 for applying stress (Pa). The cross-linked polymer sample 1401 was produced from a resin composition comprising the prepolymer comprising second cyclic carbonate 206 (shown in FIG. 2A) and the diluent 303 according to an embodiment of the invention.

(106) The experimental set-up 14A comprises four different stages; (i) heat, no load, wherein the cross-linked polymer sample 1401 is heated with no stress applied; (ii) load under heat, wherein the cross-linked polymer sample 1401 is heated with stress applied; (iii) unload while cool, wherein the cross-linked polymer sample 1401 is cooled with no stress applied; (iv) heat and recover, wherein the cross-linked polymer sample 1401 is heated and no stress is applied, in which time it is allowed to recover to its original shape. The graph 14B shows the data from the experimental set-up 14A through stages (i) to (iv).

(107) Advantageously, the cross-linked polymer sample 1401 exhibits shape memory properties. More advantageously, the glass transition temperature (T.sub.g) of the cross-linked polymers of the present invention is tunable. Therefore, wherein the cross-linked polymer sample 1401 is used as a medical device, the glass transition temperature (T.sub.g) can be tailored for shape restoration/self-deployment of different clinical devices when inserted into the human body. For example, above the T.sub.g, the polymer may enter a rubbery state in which it may be deformed into any shape. When the material is cooled below the T.sub.g, the deformation is fixed and the shape remains stable. At this stage, the material lacks the rubbery elasticity and is rigid. However, the original shape may be recovered by heating the material above the T.sub.g. In medical applications, this is useful because devices made of SMPs may be fitted at a temperature below the T.sub.g, but when in place, the devices become softer and more comfortable inside the human body.

(108) Referring also to FIG. 15, there is shown a series of photographs 15 illustrating the shape recovery of a model SMP over the course of 9 minutes, according to an embodiment of the invention. The series of photographs 15 were taken at intervals over the course of 540 seconds to show the shape recovery of a model SMP 1501. In this case, the model SMP was fabricated from a prepolymer, the prepolymer being fabricated from prepolymer 102 (FIG. 1), which was chain extended with isophorone diisocyanate 208 and cross-linked with diluent 303.

(109) Advantageously, the cross-linked polymers 1301, 1401, and 1501 that were tested demonstrated greater than 99% strain recovery, with stresses on the order of less than 180 kPa when measured in compression using dynamic mechanical analysis with strains of approximately 40%. It was shown that strain fixity was dependent on the thermomechanical properties, as those compositions with lower glass transition temperatures (T.sub.g) are not capable of maintaining a fixed shape at ambient conditions.

(110) It was shown that prepolymers comprising only the second cyclic carbonate 206 became brittle and more likely to suffer a failure during shape memory testing under dry conditions. While this limitation disappears during solvated testing, it is a possible limitation for shape setting for applications requiring high recoverable strains. Greater compressive strains were tested using compressive mechanical testing, with these materials possessing compressibility up to ca 90% without compromising the strain recoveries.

(111) Without wishing to be bound by any theory, it is thought that the cross-linked polymer structure (e.g. bonded covalently) defines the original or primary shape of the polymer. The presence of urethane linkages advantageously further allows the formation of hydrogen bonds within the cross-linked polymer structure. This drives fixation of the secondary shape, which enables the cross-linked polymers of the present invention to exhibit shape memory properties.

(112) Referring now to FIG. 16A, there is shown a graph 16A for the degradation of the cross-linked polymers 1601, 1602, 1603, 1604, 1605 according to some embodiments of the invention. The graph 16A shows the mass remaining (%100) of the cross-linked polymers 1601, 1602, 1603, 1604, 1605 versus time in hours, from zero to one hundred hours. The cross-linked polymers 1601, 1602, 1603, 1604, 1605 were incubated in a solution at 37° C. unless being dried or weighed.

(113) Cross-linked polymer 1601 comprises the cross-linked polymer 604. Cross-linked polymers 1602 and 1603 each comprise a prepolymer, each prepolymer comprising different copolymers of first cyclic carbonate 202 and second cyclic carbonate 206. Cross-linked polymer 1604 comprises a cross-linked polymer comprising a prepolymer comprising second cyclic carbonate 206. Cross-linked polymer 1605 comprises the cross-linked polymer 603.

(114) Referring also to FIG. 16B, there is shown a graph 16B for the degradation of a cross-linked polymer according to some embodiments of the invention. The graph 16B shows the mass remaining (% 100) of the cross-linked polymer versus time in different concentrations of sodium hydroxide, and also in PBS buffer. There is shown the degradation profile of the cross-linked polymer in 5M NaOH (1606), 1M NaOH (1607), 0.1M NaOH (1608), and in PBS buffer solution (1609). The cross-linked polymer incubated in a solution at 37° C. unless being dried or weighed.

(115) Referring also to FIG. 16C, there is shown a graph 16C showing the normalised storage modulus versus time (hours) of a series of the cross-linked polymers 1609, 1610, 1611 according to some embodiments of the invention.

(116) The cross-linked polymer 1609 was fabricated from a prepolymer, the prepolymer comprising the first cyclic carbonate 202. The cross-linked polymer 1610 was fabricated from a prepolymer, the prepolymer comprising the first cyclic carbonate 202 and the second cyclic carbonate 206. The cross-linked polymer 1611 was fabricated from first cyclic carbonate 202 and the second cyclic carbonate 206.

(117) The cross-linked polymers 1609, 1610, 1611 were incubated in a solution at 37° C. unless being dried or weighed. Dynamic mechanical analysis (DMA) was performed on samples in hydrolytic solution. This allowed examination of the cross-linked polymers 1609, 1610, 1611 in a simulated environment, which is advantageous if the cross-linked polymers of the present invention are to be used as load bearing biomaterials.

(118) Advantageously, the rate of degradation, of the cross-linked polymers of the present invention may be tuned or controlled. This is achieved by modifying the resin composition to result in a different cross-linked polymer structure. For example, the diluent composition and concentration may be modified to control the rate of degradation of the resulting cross-linked polymer.

(119) The rate of degradation is also affected by the glass transition temperature (T.sub.g) and the hydrophobicity of the cross-linked polymer, which is in turn controlled by the resin composition. For example, the inclusion of the second cyclic carbonate 206 in the resin composition increases the hydrolytic stability, and also reduces swelling during degradation. In contrast, inclusion of fourth diluent 304, which is diallyl phthalate, increases the hydrolytic stability and also increases the swelling during degradation.

(120) Referring first to FIG. 17A, there is shown a graph 17A showing cytocompatibility testing using pre-osteoblasts of a cross-linked polymer, according to some embodiments of the invention. Cytocompatibility testing of the cross-linked polymers according to some embodiments of the invention was performed by measuring cell viability using pre-osteoblasts on 2D surfaces and 3D surfaces. The 2D surfaces were spin-coated and compared with bare glass slides as well as PLLA films. No statistical differences were found between the surfaces at 7 and 14 days. The control films displayed greater initial compatibility at day 1 and day 3.

(121) Referring also to FIG. 17B, there is shown a selection of images 17B showing the spread of cells across the cross-linked polymer, according to some embodiments of the invention. Porous scaffolds comprising a cross-linked polymer with pore sizes ranging from 200 to 1500 μm were then printed, cleaned, and seeded with cells before incubating for 7 days. A series of images 17B1, 17B2 and 17B3 were taken at 1, 2 and 7 days respectively. The image 17B3 shows proliferation, cell spreading of cells across the porous scaffold comprising cross-linked polymer. This shows that the cross-linked polymers of the present invention have excellent biocompatibility.

(122) Advantageously, the porous scaffolds comprising the cross-linked polymer according to an embodiment of the invention allowed for cellular infiltration and adhesion, with cells climbing the walls over the course of days to completely infiltrate the samples. No pore size was found to be superior, although qualitatively the 500 μm appeared to have the best dispersion of pre-osteoblasts.

(123) Advantageously, the cross-linked polymers of the present invention display dry moduli values that range from 1 MPa to 2 GPa without requiring further additives or composites. At 37° C. in PBS, the moduli values are more representative for medical device applications; the range of moduli values is approximately 1 MPa to 0.8 GPa. Failure of the materials occurred more rapidly in compositions that do not possess shape memory (compositions containing only carbonate as the main chain linkage). Without wishing to be bound by theory, it is thought that the inclusion of the urethane linkages allowed for increase in strain to failure whilst providing a method of finely tuning moduli and glass transition temperature (T.sub.g).

(124) To further exemplify the invention, reference is also made to the following non-limiting Examples.

EXAMPLE 1

(125) A prepolymer of first cyclic carbonate 202 (Prepolymer 604) was synthesised according to the protocols described in IA Barker et. al., Biomaterials Science, 2014, 2, 472-475; and also in Y He et. al., Reactive and Functional Polymers, Vol. 71, Issue 2, February 2011, p. 175-186. The .sup.1H and .sup.13C NMR spectra of Prepolymer 604 are shown in FIG. 2D.

(126) Prepolymer 604 (1.005 g) was added to a vial (80% of ene groups, 0.005 mol). Diluent 301 (1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione), (0.312 g, 20%-ene groups, 0.001 mol) was added to the vial. Cross-linker 401 (pentaerythritol tetrakis(3-mercaptopropionate), (0.734 g, 100% thiol end groups, 0.002 mol) was added to the resin mixture. Propylene carbonate (0.615 g, 30% wt % of final resin, 0.006 mol). The mixture was mixed until homogenous. Irgacure 819® by BASF (0.020 g, 0.01 wt. % of resin composition before propylene carbonate addition) was added to the vial and mixed for 5 minutes. Curing was performed at 405 nm for 1 hour followed by 24 hour cure ramped from room temperature to 120° C. to afford the cross-linked polymer of Example 1.

EXAMPLE 2

(127) Prepolymer 604 (5.000 g, 0.004 mol) was reacted with stoichiometric amounts of isophorone diisocyanates (0.800 g, 0.004 mol) in a chain extension reaction to form a prepolymer comprising a urethane linkage (Prepolymer of Example 2).

(128) The resulting prepolymer comprising a urethane linkage (1.005 g) was added to a vial (80% of ene groups, 0.005 mol). Diluent 301 (1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione) (0.312 g, 20%-ene groups, 0.001 mol) was added to the vial. Cross-linker 401 (pentaerythritol tetrakis(3-mercaptopropionate) (0.734 g, 100% thiol end groups, 0.002 mol) was added to the resin composition mixture. Propylene carbonate (0.615 g, 30% wt % of final resin, 0.006 mol) was added and mixed until homogenous.

(129) Irgacure 819® by BASF (0.020 g, 0.01% wt of resin before addition of the propylene carbonate) was added to the vial and mixed for 5 minutes. Curing was performed at 405 nm for 1 hour followed by 24 hour cure ramped from room temperature to 120° C. to afford the cross-linked polymer of Example 2.

EXAMPLE 3

(130) Isophorone diisocyanate (7.655 g, 0.034 mol) was reacted with allyl alcohol (4.000 g, 0.034 mol) and the resulting mixture was purified to produce diluent 303. The .sup.1H NMR spectrum and the .sup.13C NMR spectrum of the diluent 303 is shown in FIG. 3B.

(131) Prepolymer 604 (1.711 g, 0.009 mol) was added to a vial followed by diluent 303 (0.359 g, 0.001 mol) and diluent 301 (0.265 g, 0.001 mol). Cross-linker 401 (1.250 g, 0.003 mol) was added to the vial followed by propylene carbonate (30 wt. %, 1.075 g, 0.010 mol).

(132) Irgacure 819® by BASF (0.018 g, 0.01% wt of resin before addition of the propylene carbonate) was added to the vial. Curing was performed at 405 nm for 1 hour followed by 24 hour cure ramped from room temperature to 120° C. to afford the cross-linked polymer of Example 3.

(133) As described above, the cross-linked polymer of Example 1 and Example 3 were fabricated from a resin composition comprising a prepolymer with carbonate linkages only (the prepolymer had no urethane linkages). The urethane linkages in the cross-linked polymer of Example 1 were provided by reaction of the diluent 301 with the prepolymer 604 only. The urethane linkages in the cross-linked polymer of Example 3 were provided by reaction of diluents 301 and 303 with the prepolymer only (Prepolymer of Example 3).

(134) In contrast, the cross-linked polymer of Example 2 was fabricated from a resin composition comprising a prepolymer with at least one urethane linkage (via the chain extension reaction with a diisocyanate). Further urethane linkages in the cross-linked polymer of Example 2 were provided by reaction of the diluent 301 with the chain extended prepolymer (Prepolymer of Example 2).

(135) Protocol for Post-Polymerisation Functionalisation: Alkylation of Cross-Linked Polymers

(136) The solid prepolymer (100 mg) was completely immersed in acetone in a vial at room temperature. Dodecane thiol (2.000 g) was added to the vial and dissolved. Irgacure 819® by BASF (0.050 g) was dissolved in the solution.

(137) The vial was irradiated using 405 nm for 1 hour. The resulting cross-linked polymer was removed from solution and irradiated for an additional 1 hour before allowing to dry overnight at room temperature to afford the alkylated cross-linked polymer.

(138) Protocol for Halogenation of Cross-Linked Polymers

(139) Protocol A: Iodine monochloride (2.000 g, 0.012 mol) was added to a solution of first cyclic carbonate 202 (2.000 g, 0.010 mol) and stirred at 60° C. for 24 hours. The resulting halogenated product was polymerised to form a prepolymer, which was subsequently used in a resin composition to fabricate a halogenated cross-linked polymer.

(140) Protocol B: Prepolymer, e.g. prepolymer 604 (2.00 g, 0.001 mol) was added to iodine monochloride (2.000 g, 0.012 mol) and stirred at 60° C. for 24 hours. The resulting halogenated prepolymer was subsequently used in a resin composition to fabricate a halogenated cross-linked polymer.

(141) Protocol C: The appropriate solid cross-linked polymer (100 mg) was added to a vial of iodine monochloride (2.000 g) at 50° C. and allowed to sit for 48 hours to afford a halogenated cross-linked polymer.

(142) In summary, the resin compositions and the cross-linked polymers of the present invention exhibit a number of highly advantageous properties including: Degradability—the cross-linked polymers of the present invention are degradable in the human body, i.e. the cross-linked polymers degrade into small molecules, which are non-toxic and may be excreted or metabolised. The rate of degradation is tunable based on the ratio of the components within the resin composition. Biocompatible and non-toxic—advantageously, the cross-linked polymers of the present invention are biocompatible and non-toxic. In addition to the degradation products being non-toxic, the synthesis of any of the components of the resin composition, and/or the synthesis of the cross-linked polymer itself does not use any toxic reagents or catalysts, e.g. tin catalysts and so on. Shape memory properties—the cross-linked polymers of the present invention exhibit shape memory properties. Without wishing to be bound by theory, it is believed that the urethane linkages in the cross-linked polymer impart particularly advantageous shape memory properties, and the polycarbonate linkages impart degradability to the material. These properties are advantageous for use of the cross-linked polymers in devices for medical applications. Processability—the resin compositions of the present invention are suitable for processing into a variety of geometries that allow for spatiotemporal control of their behaviour. The morphology and the porosity, i.e. the pore size, pore density, can be controlled and reproduced. Advantageously, the cross-linked polymers comprise homogeneous structures, both in terms of bulk morphology and composition. The cross-linked polymers can be repeatedly and rapidly manufactured into a range of sizes allowing for the same device to be patterned across a series of sizes. The resin compositions of the present invention exhibit an appropriate viscosity for use in 3D printing using microstereolithographic apparatus. Tunability of properties—The resin composition may be varied to tune the properties of the resulting cross-linked polymer. For example, the type and concentration of the prepolymer and/or the diluent and/or the cross-linker may be adjusted to tune the shape memory properties, the biocompatibility, the glass transition temperature (T.sub.g), the degradation rate, the strain recovery, and other physiochemical and thermomechanical properties of the cross-linked polymer. The structure of the prepolymer may be varied to tune the properties of the resulting cross-linked polymer, i.e. by using different types and/or concentrations of monomer to fabricate the prepolymer. Further functionalisation of the cross-linked polymer—Post-polymerisation, the unsaturated side-chains may be functionalised to introduce functionality that is not compatible with the cross-linking process, e.g. microstereolithography. The post-polymerisation functionality enables the cross-linked polymer to exhibit other advantageous properties, e.g. increased x-ray density, and increase hydrophobicity. The unsaturated side-chains may also be functionalised with biomolecules for recognition, for example.

(143) It will also be appreciated by those skilled in the art that any number of combinations of the aforementioned features and/or those shown in the appended drawings provide clear advantages over the prior art and are therefore within the scope of the invention described herein.