Shape-memory polymer

Abstract

The invention relates to use of a polymer (I) as a precursor of a shape-memory polymer, wherein the polymer (I) comprises a backbone which is end-capped by a crosslinkable end-capping unit comprising a moiety having a crosslinkable functionality, wherein the backbone comprises a copolymer of a cyclic carbonate selected from the group consisting of trimethylene carbonate, ethylene carbonate, propylene carbonate, styrene carbonate and glycerol carbonate and a comonomer selected from the group consisting of ε- caprolactone, α-acetolactone, β-propiolactone, γ-butyrolactone, δ- valerolactone, β-butyrolactone, γ-caprolactone, γ-octalactone, γ-nonalactone, δ- decalactone, γ-decalactone, ω-pentadecalactone, diglycolic anhydride, glycolide,lactide, norcamphor lactone, verbanone lactone, dihydrocarvide, wherein the lactone is unsubstituted or substituted by halogen or C1-C12 alkyl, and combinations thereof.

Description

[0001] SHAPE-MEMORY POLYMER

[0002] The present invention relates to use of a polymer as a precursor of a shape-memory polymer. The invention further relates to a shape-memory polymer obtained from such polymer. The invention further relates to a shape-memory article comprising such shapememory polymer and applications thereof.

[0003] The ability to create biocompatible 3D scaffolds with temporal properties, using a stimulus to trigger shape changes, opens up new possibilities for designing smart biomedical devices. While shape changes of biomedical devices are mainly limited to swelling / shrinking (volume increase / decrease), the use of shape memory materials (SMMs) brings the opportunity to transform completely the material’s shape. This important class of stimuli-responsive materials, with the capability to change the shape in response to an external stimulus, have a great potential for biomedical applications, such as tissue-engineered scaffolds, cardiovascular grafts, stents, and drug delivery systems, among others.

[0004] Shape memory polymers (SMPs) represent the most useful class of SMMs for biomedical applications owing to material properties (e.g. mechanics, hydrophilicity) closer to native tissues and their biocompatibility. A small device made of SMPs can be inserted into the body and then adopt its larger functional shape, facilitating minimally invasive procedures. Furthermore, biodegradable and bioresorbable SMPs can also prevent a second surgery for removing implanted materials, or support tissue formation and integration.

[0005] SMPs have gained even more attention since 4D printing emerged in the last decade. By merging additive manufacturing with SMPs, we are now able to fabricate complex stimuli- responsive structures with programmable morphing changes. Among the additive manufacturing techniques, light-based fabrication like Digital Light Processing (DLP) results in high-resolution and fast printing times. DLP has been recently explored in regenerative medicine owing to high accuracy to print complex scaffolds like vascular branches. However, the lack of customizable biodegradable and biocompatible resins made of shape memory polymers remains a significant bottle-neck. The shape memory properties of polycaprolactone (PCL), together with its biocompatibility and biodegradability, has motivated an increasing number of researchers to explore the macromolecular design for modulating the shape recovery (time and temperature, which trigger the response). Most of the approaches include covalently crosslinked low molecular weighted PCL, where the crosslinks are indispensable to endow the material with shape memory effect.

[0006] WO2021 / 224417 discloses a precursor of a shape-memory polymer, the precursor comprising a polymer backbone connected to crosslinkable end-capping urethane- and / or urea units, wherein the polymer backbone has an amorphous backbone. The polymer backbone comprises polylactic acid (PLA) or co-polymers thereof.

[0007] It is an objective of the present invention to provide a shape memory polymer which can be used for various applications such as biomedical applications.

[0008] Accordingly, the present invention provides use of a polymer (I) as a precursor of a shapememory polymer, wherein the polymer (I) comprises a backbone which is end-capped by a crosslinkable end-capping unit comprising a moiety having a crosslinkable functionality, wherein the backbone comprises a copolymer of a cyclic carbonate selected from the group consisting of trimethylene carbonate, ethylene carbonate, propylene carbonate, styrene carbonate and glycerol carbonate and a comonomer selected from the group consisting of e-caprolactone, a-acetolactone, - propiolactone, y-butyrolactone, b-valerolactone, p-butyrolactone, y-caprolactone, y- octalactone, y-nonalactone, b-decalactone, y-decalactone, w-pentadecalactone, norcamphor lactone, verbanone lactone, lactide, glycolide, diglycolic anhydride, dihydrocarvide and combinations thereof, wherein the lactone is unsubstituted or is substituted by halogen or C1-C12 alkyl.

[0009] It was surprisingly found that a shape-memory polymer made from a crosslinkable polymer having a backbone comprising a copolymer of the cyclic carbonate according to the invention has desirable properties for biomedical applications, especially applications wherein the shape change due to the shape-memory property is desired at body temperature. Advantageously, the cyclic carbonate used in the copolymer according to the invention has no acidic organic compounds generated during hydrolysis, which is more suitable for biomedical applications. The cyclic carbonate allows for more softness and ductility to be introduced into the networks (low glass transition temperature Tg), increasing the range of applications. Furthermore, the reaction rate and degradation (surface erosion) of the copolymer comprising the cyclic carbonate is different from that of polyester. The physical properties of the cyclic carbonate as a low Tg and flexible backbone enable a wide variety of biomedical uses.

[0010] The invention further relates to a shape-memory polymer obtained by crosslinking the polymer (I).

[0011] Shape-memory polymers (SMPs) are polymers that have the ability to return from a deformed state (temporary shape) to their original (permanent) shape when induced by an external stimulus (trigger), such as temperature change. The polymer is capable of changing its shape in a controlled manner when the temperature increases above what is known as the transition temperature. In a shape-memory polymer, a distinction is made between a permanent and a temporary shape. The polymer is first brought to its permanent shape by a suitable method. The polymer is then brought to its desired temporary shape at an increased temperature and then cooled to fix the temporary shape. The permanent shape is in memory while having the temporary shape. Heating of the polymer to a temperature higher than the transition temperature for a change of morphology triggers the shape memory effect and thus leads to resumption of the permanent shape from memory.

[0012] The term “precursor of a shape memory polymer” is herein understood to mean a polymer which can be crosslinked to obtain a shape memory polymer.

[0013] The polymer (I) has a backbone comprising a copolymer of a cyclic carbonate and a comonomer specified herein. The backbone is end-capped by a crosslinkable endcapping unit comprising a moiety comprising a crosslinkable functionality. It will be appreciated that the polymer (I) may also have end-capping units attached to the backbone that are not crosslinkable, i.e. the polymer (I) may further comprise end-capping units which do not comprise a moiety comprising a crosslinkable functionality.

[0014] Backbone

[0015] The backbone of the polymer (I) comprises a copolymer of a cyclic carbonate.

[0016] The cyclic carbonate is selected from the group consisting of trimethylene carbonate, ethylene carbonate, propylene carbonate, styrene carbonate and glycerol carbonate and combinations thereof. Most preferably, the cyclic carbonate is trimethylene carbonate.

[0017] The comonomer in the polymer (I) is selected from e-caprolactone, a-acetolactone, p- propiolactone, y-butyrolactone, b-valerolactone, p-butyrolactone, y-caprolactone, y- octalactone, y-nonalactone, b-decalactone, y-decalactone, w-pentadecalactone, norcamphor lactone, verbanone lactone, lactide, glycolide, diglycolic anhydride, dihydrocarvide and combinations thereof, wherein the lactone is unsubstituted or is substituted by halogen or C1-C12 alkyl.

[0018] Examples of the substituted lactone include chloro-e-caprolactone and a-alkyl-e- caprolactone. Preferably, the lactone is unsubstituted.

[0019] Preferably, the comonomer is selected from e-caprolactone, a-acetolactone, p- propiolactone, y-butyrolactone, b-valerolactone, p-butyrolactone, y-caprolactone, y- octalactone, y-nonalactone, b-decalactone, y-decalactone, w-pentadecalactone, norcamphor lactone, verbanone lactone, glycolide, diglycolic anhydride, dihydrocarvide and combinations thereof, wherein the lactone is unsubstituted or is substituted by halogen or C1-C12 alkyl.

[0020] More preferably, the comonomer is selected from E- caprolactone, y-butyrolactone, 6- valerolactone, p-butyrolactone, y-caprolactone, y-octalactone, y-nonalactone, 6- decalactone, y-decalactone, diglycolic anhydride, glycolide, norcamphor lactone, wherein the lactone is unsubstituted or substituted by halogen or C1-C12 alkyl, and combinations thereof. Preferably, the comonomer is selected from e-caprolactone, lactide and glycolide, more preferably selected from e-caprolactone and glycolide. Most preferably, the comonomer is e-caprolactone.

[0021] Most preferably, the backbone of the polymer (I) comprises a copolymer of trimethylene carbonate and e-caprolactone.

[0022] Preferably, the weight ratio between the comonomer and the cyclic carbonate in the polymer (I) is 10:90 to 90:10, more preferably 50:50 to 90:10, more preferably 70:30 to 90:10, more preferably 70:30 to 80:20. An increase in the amount of the cyclic carbonate in the copolymer results in a lower melting temperature of the copolymer or the melting temperature not being observed. This may result in the shape-memory article according to the invention to have a switching temperature not suitable for desired applications.

[0023] Preferably, the polymer (I) and / or the backbone of the polymer (I) has Mn of 1.0 to 15 kDa as determined by 1 H NMR.

[0024] More preferably, the polymer (I) and / or the backbone of the polymer (I) has Mn of 1.0 to 10 kDa as determined by 1 H NMR. This ensures that the shape-memory polymer obtained from the polymer (I) can be formed into a desired shape by various methods such as DLP without the problem of removing it from the equipment.

[0025] End-capping unit

[0026] Preferably, the moiety comprising the crosslinkable functionality is selected from the group consisting of (meth)acrylate, (meth)acrylamide, coumarin, thiol, norbornene, vinyl ether, vinyl ester, (meth)acryloyl and combinations thereof.

[0027] Preferably, the moiety comprising the crosslinkable functionality is (meth)acrylate, (meth)acrylamide or (meth)acryloyl, most preferably (meth)acrylate or (meth)acryloyl.

[0028] Particularly preferably, the (meth)acrylate or the (meth)acrylamide is selected from the list consisting of

[0029] 2- hydroxyethyl acrylate, 2- hydroxyethyl methacrylate, ethoxylated and / or propoxylated pentaerythritol tri(meth)acrylate (EPPETA), pentaerythritol tri(meth)acrylate (PETA), dipentaerythritol penta(meth)acrylate (DPEPA), propoxylated glycerol di(meth)acrylate (PGDA), glyceroldiacrylate (GDA), oligo(ethylene oxide) (meth)acrylate (PEA), poly(s-caprolactone) (meth)acrylate (PCLA) or the corresponding (meth)acrylamides and combinations thereof.

[0030] In some embodiments, the moiety comprising the crosslinkable functionality is directly bonded to the backbone. This has an advantage that it can increase crosslink density and impact mechanical properties (e.g. toughness) for a wider range of applications.

[0031] In particularly preferred embodiments, the polymer (I) is obtained by reacting a (meth)acryloyl halide such as acryloyl chloride with the backbone. This has an advantage that it provides less synthetic steps to the desired product.

[0032] In some embodiments, the end-capping unit comprises a urethane- and / or urea- containing moiety between the backbone and the moiety comprising the crosslinkable functionality. Preferably, the end-capping unit comprises a urethane-containing moiety between the backbone and the moiety comprising the crosslinkable functionality. This has advantages that the degradation profile can be altered, reinforcing supramolecular hydrogen bonds can be added, the biobased content of the resin can be increased, and functional groups on the urethane spacer can be used for post-fabrication functionalization of the surface with (for example) bioactive molecules.

[0033] Preferably, said urethane- and / or urea-containing moiety is a polyisocyanate moiety, such as diisocyanate moieties and trimers of polyisocyanates.

[0034] Suitable examples of diisocyanate moieties include L-lysine diisocyanate ethyl ester.

[0035] Other examples of diisocyanate moieties include cycloaliphatic diisocyanates, aliphatic diisocyanates and aromatic diisocyanates; preferably 5-isocyanato-1-isocyanatomethyl-1 ,3,3- trimethylcyclohexane (IPDI), 1 ,T-methylene bis[4-isocyanatocyclohexane] (H12MDI), L-2,6- Diisocyanatohexanoic acid ethyl ester (LDI), 1 ,6-diisocyanatohexane (HDI), 1 ,6-diisocyanato- 2,4,4-trimethylhexane (TMDI), 2,4-diisocyanatotoluene (TDI), 1 ,4- diisocyanatobenzene (BDI), 1 ,3- meta-tetramethylxylylene diisocyanate (TMXDI), and 1 ,T- Methylenebis(4- isocyanatobenzene) (MDI); and derivatives thereof, such as 1 ,6- diisocyanatohexane biuret and isocyanurate.

[0036] Suitable examples of trimers of polyisocyanates include a trimer of 5-isocyanato-1- isocyanatomethyl-1,3,3-trimethylcyclohexane (trimer of isophorone diisocyanate, IPDI).

[0037] Preferably, the end-capping unit comprises L-lysine diisocyanate ethyl ester bonded to the backbone.

[0038] In some embodiments, the moiety comprising the crosslinkable functionality is directly bonded to the urethane- and / or urea-containing moiety.

[0039] In some embodiments, the end-capping unit may comprise a spacer between the urethane- and / or urea-containing moiety and the moiety comprising the crosslinkable functionality.

[0040] Suitable examples of the spacer include (saturated) oligo-ethers (such as ethylene oxide and propylene oxide) and (saturtated) oligo-esters. In accordance with the present embodiment, the spacers can comprise heteroatoms (atoms other than carbon atoms), such as O, S or N, and have multiple carbon atoms.

[0041] In particularly preferred embodiments, the polymer (I) is obtained by reacting a reaction product of the urethane- and / or urea-containing moiety (such as L-lysine diisocyanate ethyl ester) with the moiety comprising the crosslinkable functionality (such as 2- hydroxyethyl acrylate) with the backbone. This has an advantage that the polymer synthesis provides more steps for quality control and allows characterization of the LDI- HEA adduct to decrease chain extension. A further advantage is its biobased character and ability to be post polymerization functionalized.

[0042] Preferably, the polymer (I) has a degree of acrylation of 35 to 95 %, preferably 50 to 90%, more preferably 60 to 85%. This has an advantage that the gel content of the network is high, while also allowing a degree of freedom for tuning the crosslink density. In the context of the present invention, by means of the term “degree of acrylation”, as used herein, unless indicated otherwise, reference is made to the content of (meth)acrylic moieties measured as (meth)acrylate density, which was determined by quantitative NMR. For example, triethylene glycol (TEG) was used as an internal reference to determine the acrylate content (M) through the following formula: where luindicates the integration of the NMR peak between 5.8-6.5ppm, which peaks correspond to the acrylate. Nuis the amount of hydrogens associated with the peak of the acrylate group. While ITEG and NTEG indicate the integration of the peaks between 3.5- 3.8 ppm, and the number of hydrogels associated with those peaks, respectively. The formula for the determination of the methacrylate can be obtained in a similar way, in accordance with known methodologies.

[0043] The invention further provides a shape-memory article comprising the shape-memory polymer, wherein the shape memory-article is obtained by a process comprising the steps of: i) providing the polymer (I), ii) forming the polymer (I) into a first article having a first shape, iii) crosslinking the polymer (I) of the first article such that the fist shape is maintained, iv) heating the first article and deforming the first article to obtain a second, deformed article having a second shape different from the first shape and v) cooling the second, deformed article such that the second shape is maintained.

[0044] The process for obtaining the shape-memory article according to the invention comprises the step of i) providing the polymer (I).

[0045] The polymer (I) may be provided by a process comprising the steps of: a) copolymerizing the cyclic carbonate and the comonomer to obtain the copolymer and b) end-capping the copolymer by the crosslinkable end-capping unit comprising a moiety having a crosslinkable functionality.

[0046] Step ii) The process for obtaining the shape-memory article according to the invention further comprises the step of ii) forming the polymer (I) into a first article having a first shape. The first shape is the ‘permanent’ shape to which the shape-memory returns at temperatures above the transition temperature.

[0047] Step ii) may comprise the step of mixing the polymer (I) with a photo-initiator and an optional diluent to obtain a crosslinkable composition and forming the crosslinkable composition into the first article. A diluent can be used for increasing the viscosity of the crosslinkable composition. A diluent desirably has a relatively low volatility with a boiling point of at least 200 °C and is capable of solubilizing the polymer (I) to form a homogeneous solution.

[0048] The amount of the photo-initiator may be 0.1 to 3.0 wt% of the total of the polymer (I) and the diluent. Suitable examples of the photo-initiator are known and are described e.g. in WO2021 / 224417, p.15, I.34- p.16, 1.15.

[0049] The diluent may be a reactive diluent or a non-reactive diluent.

[0050] The use of a reactive diluent has an advantage that the diluent becomes part of the shape-memory polymer and a solvent waste can be avoided. The reactive diluent is advantageously a compound which has ethylenic unsaturation. Examples of the reactive diluent include 2-(2-ethoxyethoxy)ethyl acrylate (EOEOEA), hydroxyethylmethacrylate and N-vinyl pyrrolidinone. According to the invention, the polymer used as a precursor of the shape-memory polymer is end-capped since mixing of a reactive diluent with the polymer (I) without the end-capping group will not result in a free standing object.

[0051] Examples of the non-reactive diluent include tetrahydrofuran (THF).

[0052] The weight ratio of the polymer (I) to the diluent may be selected such that the resulting composition has a suitable viscosity for processing while avoiding a large increase in the mechanical properties of the crosslinked polymer. The weight ratio of the polymer (I) to the diluent may be 10:90 to 90:10, for example 50:50 to 80:10. Step ii) may involve various methods such as extrusion, injection molding, compression molding, blow molding, sheet extrusion, coating (e.g. spin coating, dip coating, spray coating), wet spinning, electrospinning, fused deposition modelling, multiphoton lithography, stereolithography (SLA printing), Digital Light Processing (DLP), film casting, porogen leaching, extrusion based 3D-printi ng , inkjet 3D- printing, spray drying, cryogenic treatment, crosslinkable micelles, electro-spraying, melt-electro writing, doctor blading. Examples of extrusion based 3D-printing include Fused Filament Fabrication (FFF), syringe printing, bioplotting. These methods are per se known and are described e.g. in WO2021 / 224417, p.14, 1. 18 — p.15, 1.32, incorporated herein by reference.

[0053] Preferably, step ii) is performed by Digital Light Processing.

[0054] The process further comprises the step of iii) crosslinking the polymer (I) of the first article such that the fist shape is maintained. This may be performed by irradiating the first article by electromagnetic irradiation e.g. UV-Vis, near IR, IR.

[0055] The process further comprises the step of iv) heating the first article and deforming the first article to obtain the deformed article having a second shape different from the first shape.

[0056] The heating may be performed up to a temperature at which deformation to a desired second shape can occur. This temperature may be slightly above the glass transition temperature of the polymer (I). A mechanical stress is applied to deform the first shape into the second shape.

[0057] The process further comprises the step of v) cooling the second, deformed article such that the second shape is maintained.

[0058] The deformed article having a second shape is cooled while the stress is maintained during cooling. Once the shape is cooled below the glass transition temperature, the shape will be maintained when the stress is removed. This shape is the temporary shape. Use of shape memory article

[0059] The shape memory article having the temporary shape (second shape) returns to the first shape by subjecting the deformed article to a temperature above a transition temperature such as the glass transition temperature.

[0060] Preferably, the shape memory article has a transition temperature of 0 to 150 °C, more preferably 20 to 120 °C. For medical applications, transition temperatures of 35 to 55 °C are most preferred.

[0061] Herein, “transition temperature” may be understood as a temperature at which the article returns from the second shape to the first shape within 2 hours, within 1 hour, within 30 minutes, within 10 minutes or within 5 minutes.

[0062] In some preferred embodiments, the shape memory article returns to the first shape after a period of 1 second to 5 minutes at 35 to 55 °C, for example 2 seconds to 3 minutes, 3 seconds to 2 minutes or 5 seconds to 60 seconds. Such relatively fast shape transition may be particularly beneficial for use of the shape memory article in a sensor, a device, stent, or scaffold in support of a minimally invasive procedure or a self-tightening degradable suture, self-folding packages, soft robotics, a cell traction force structure, shape memory stent, shape memory device to treat embolization, staples for wound closure, spinal disk structural reinforcement.

[0063] In other preferred embodiments, the shape memory article returns to the first shape after a period of 5 minutes to 2 hours at 35 to 55 °C, for example 10 minutes to 1.5 hours or 30 minutes to 1 hour. Such relatively slow shape transition may be particularly beneficial for use the shape memory article in a drug delivery system, a scaffold for the formation of artificial tissue, reconfigurable architectures for cell growth, foldable sheet for cell delivery.

[0064] The shape memory article can be used in various applications such as medical applications.

[0065] The invention provides a drug delivery system, a sensor, a device, stent, or scaffold in support of a minimally invasive procedure or a self-tightening degradable suture, a scaffold for the formation of artificial tissue, self-folding packages, soft robotics, reconfigurable architectures for cell growth, a cell traction force structure, shape memory stent, foldable sheet for cell delivery, shape memory device to treat embolization, staples for wound closure, spinal disk structural reinforcement, comprising the shape memory polymer or the shape memory article according to the invention.

[0066] Examples of minimally invasive procedure include laproscopic surgeries, delivery of stents via catheter, delivery of mesh patches via cather, delivery of cell sheets.

[0067] In some specific embodiments, the invention provides a drug delivery system, a selftightening degradable suture, a scaffold for the formation of artificial tissue, self-folding packages, soft robotics, reconfigurable architectures for cell growth, shape memory stent, foldable sheet for cell delivery, shape memory device to treat embolization, comprising the shape memory polymer or the shape memory article according to the invention.

[0068] It is noted that the invention relates to the subject-matter defined in the independent claims alone or in combination with any possible combinations of features described herein, preferred in particular are those combinations of features that are present in the claims. It will therefore be appreciated that all combinations of features relating to the composition according to the invention; all combinations of features relating to the process according to the invention and all combinations of features relating to the composition according to the invention and features relating to the process according to the invention are described herein.

[0069] It is further noted that the term ‘comprising’ does not exclude the presence of other elements. However, it is also to be understood that a description on a product / composition comprising certain components also discloses a product / composition consisting of these components. The product / composition consisting of these components may be advantageous in that it offers a simpler, more economical process for the preparation of the product / composition. Similarly, it is also to be understood that a description on a process comprising certain steps also discloses a process consisting of these steps. The process consisting of these steps may be advantageous in that it offers a simpler, more economical process. When values are mentioned for a lower limit and an upper limit for a parameter, ranges made by the combinations of the values of the lower limit and the values of the upper limit are also understood to be disclosed.

[0070] The invention is now elucidated by way of the following examples, without however being limited thereto.

[0071] Figure 1. Designing PCT copolymers for DLP printing. Schematic of the synthetic route used to obtain the PCT Ac macromonomers

[0072] Figure 2. Resin formulation and DLP printing of resins, (a) Preparation of resins, (b) Scheme of DLP printing and images of PCT Ac75:25 printed structures.

[0073] Figure 3. 3D printed scaffolds based on PCT could changed their shape at body temperature, (a) DSC graph of printed PCT Ac samples, (b) Scheme of heat-cool-heat cycle, (c) Example of heating cycling for PCTAc75:25-based closed box (temporary shape) in a water bath at 37 °C.

[0074] Figure 4. Dynamic mechanical characterization of 3D printed PCT-based scaffolds.

[0075] Storage modulus (E) vs. temperature curves of PCT Ac networks with different polymer architecture.

[0076] Figure 5. Shape-memory programmable printed PCT-based scaffolds could grab, lift and release cargo, (a) Closed box (PCTAc 70:30) released cargo at 37 °C (water bath).

[0077] (b) Gripper (PCTAc 75:25) closed upon application of heat (via heat gun) for grabbing and lifting a screw.

[0078] Materials

[0079] L-lysine diisocyanate ethyl ester (>96%, LDI) was obtained from Actu-AII chemicals, trimethylene carbonate (99%, TMC) was provided by Huizhou Foryou Medical Devices, E- caprolactone (99%, CL) and 2-hyrdroxyethyl acrylate (HEA) were obtained from Alfa Aesar, diphenyl (2, 4, 6-trimethylbezoyl) phosphine oxide (TPO) and calcium hydride (CaH2) were obtained from Sigma Aldrich, Tetrahydrofuran (anhydrous, >99%, THF), tin 2-ethyl hexanoate (92.5%, Sn(ll)Oct), methanol (99.5%) and triethylene glycol (>99%, TEG) and toluene (>99.8%, anhydrous) were obtained from Merck, 2-(2-ethoxy-ethoxy) ethyl acrylate (EOEOEA) was provided by TCI Chemicals and chloroform (98%, CHCI3) was obtained from VWR. CL was dried for 12 h over calcium hydride and distilled under reduced pressure. TMC was lyophilized for 48 h before polymerization, Sn(ll)Oct was distilled under reduced pressure before use. All other chemicals were used as received.

[0080] Synthesis of poly(caprolactone-co-trimethylencarbonate) urethane acrylate (PCTAc)

[0081] The general procedure for photo-polymerizable copolymer synthesis consists of two steps: 1) synthesis of poly(CL-co-TMC) (PCT) copolymer via ring opening polymerization of e-caprolactone and trimethylene carbonate, and 2) acrylation of poly(CL-co-TCM) copolymer. A series of PCTAc with varying monomer ratio, molecular weight, or acrylate end capping groups were synthesized. The general procedure for PCTAc 75:25 is described below as an example.

[0082] Synthesis of poly(CL-co-TMC) 75:25, 4 kDa. Typically, a 100 mL round bottom flask was equipped with a magnetic stir bar and charged with TMC (5.00 g, 49 mmol), CL (17.26 g, 147 mmol), TEG (1.16 g, 7.94 mmol) and Sn(ll)Oct (57.40 mg, 0.14 mmol). The mixture was heated to 140 °C and stirred for 24 h under a nitrogen atmosphere. The final product was then dissolved in CHCh and purified by precipitation in cold methanol (~0 °C). A viscous transparent solid was collected and dried under high vacuum for 48 h (13 g, 60%).

[0083] Acrylation of poly(CL-co-TMC) 75:25. There were two methods of acrylation explored for this formulation (75:25, 4 kDa).

[0084] In the first method, the printable copolymer (PCTAc) was prepared by reacting the PCT with the LDI-HEA end capping reagent. Briefly, LDI (3.0 g, 13.33 mmol) was dissolved in anhydrous toluene (5 mL, 47 mmol) then Sn(ll)Oct (60 mg, 0.13 mmol) was added and stirred for 10 min under a stream of dry nitrogen. A solution of HEA (1.28 g, 13.33 mmol) in anhydrous toluene (5 mL, 47 mmol) was added dropwise under vigorous stirring. After the addition of HEA the reaction was heated to 40 °C for 12 h and kept in the dark. The final product was obtained as a yellow liquid, which was used without further purification. On the other hand, PCT 75:25 (Mn: 3700 g mol-1) 10 g (2.7 mmol) was dissolved in chloroform (30 mL). Then, Sn(ll)Oct (23 mg, 0.05 mmol) was added stirred for 10 minutes before the LDI-HEA mixture in toluene (4 ml, 5.4 mmol) was added. The mixture was heated to 40 °C for 24 h. The final product was concentrated under reduced pressure and then purified by precipitation in cold methanol (0 °C). A high-viscous yellow solid (8.9 g, 85%) was obtained after drying under vacuum for 48 hours. In order to compare the effect of the acrylate end capping group on the shape memory properties, a second PCT acrylate was synthesized by reaction of PCT 75:25 with acryloyl chloride. Briefly, 5 grams (1.3 mmol) of PCT 75:254 kDa were dissolved in 30 mL of DCM, under nitrogen atmosphere, and acrylated by reaction with a four molar excess of acryloyl chloride (420 pL, 5.2 mmol), which was added dropwise, in presence of a 2.5 molar excess of TEA (460 pL, 3.25 mmol). The reaction solution was stirred overnight at room temperature. Subsequently, the polymer was precipitated in diethyl ether and filtrated twice, and finally dried under high vacuum (7 g, 75%).

[0085] Characterization

[0086] Nuclear magnetic resonance (1 H-NMR and 13C-NMR) spectra of PCT copolymers were recorded on a Bruker ASCEND™ 700 MHz NMR spectrometer equipped with TCI cryo probe™. 7 mg of the sample were taken and dissolved into 700 pL deuterated chloroform (CDCh). Chemical shifts were studied and correlated to their chemical structure using MestReNova.

[0087] Gel permeation chromatography (GPC) was conducted using / V, / V-dimethylformamide (DMF) containing 0.1 wt% LiBr as eluent and the sample concentration was fixed to 1 g L-1. The GPC Shimadzu system was comprised of an autosampler, a Shodex KD-G 4A guard column (4.6 x 10 mm) with 8 pm beads, followed by two Shodex KD-802 (5 pm, 8 x 300 mm) and KD-804 (7 pm, 8 x 300 mm) columns, a refractive index detector and a photodiode array detector at 50 °C with a flow rate of 1 mL min-1. The GPC system was calibrated against linear poly (methyl methacrylate) standards with molecular weights ranging from Mp = 600 to 265300 Da. The samples were filtered through polytetrafluorethylene (PTFE) membranes with a pore size of 0.2 pm prior to injection.

[0088] Fabrication of 3D scaffolds

[0089] Preparation of printing resins. UV curable resins were prepared by mixing poly(CL-co- TMC) acrylates (70 wt%) with the diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO, 1 wt%) as photo-initiator and 2-(2-ethoxyethoxy)ethyl acrylate (EOEOEA, 29 wt%) as a reactive diluent. The resins were heated to 50 °C and mixed manually until homogenous.

[0090] 3D printing. 3D scaffolds (shapes: open box and gripper) were fabricated using a commercially available Digital Light Projecting DLP printer (ARM 10, Roland, Geel, Belgium) with a customized vat and printhead. The scaffolds were printed at temperatures of around 55 °C, via a heated vat. The printing parameters used include a layer thickness of 50 urn and a curing time of 3.5 s. After manufacturing, the scaffolds were washed two times with acetone and ethanol to remove all the unreacted resin. The scaffolds were then post-cured in a UV oven at 365 nm (10 mW cm-2) for 5 min from both top and bottom sides.

[0091] Shape-Memory behavior

[0092] Dynamic scanning calorimetry was performed using a TA Instrument Q 2000 DSC to analyze the thermal properties of photo-crosslinked PCT-based resins. Samples were measured in a range from -80 °C to 100 °C using heat-cool-heat cycles, using 10 °C / min temperature rate. The melting point was determined at the maximum of the endotherm peak.

[0093] Shape-memory testing at body temperature. The printed 3D structures (open box, original shape) for each PCTAc formulation were heated to 40 °C followed by deformation to the desired configuration (closed box, temporary shape) under an external force. The temporary shape was fixed by cooling in the freezer (4 °C). The shape recovery was achieved by submerging the structure in a water bath at 37°C.

[0094] A gripper shaped structure (based on PCTAc 75:254 kDa copolymer) was also printed and a similar heating-cooling-heating cycle was performed. In this case, the shape recovery was achieved by using a heat gun in order to grab and lift a screw from the bench.

[0095] Dynamic mechanical testing. The quantitative shape-memory tests were carried out using a dynamic mechanical analyzer to determine the storage modulus (E’) as a function of temperature. Printed samples (40 mm * 10 mm x 0.5 mm) were subjected to a cantilever beam model at a frequency of 1 Hz. The temperature was increased at a heating rate of 5 °C / min from -20 °C to 120 °C.

[0096] Results and Discussion

[0097] Synthesis and characterization of macromonomer library Poly(caprolactone-co-trimethylenecarbonate) (PCT) urethane acrylates (PCTAc) as shown in Table 1 were obtained by the synthetic route shown in Figure 1.

[0098] Table 1. PCT copolymers chemical and thermal analysis.

[0099] Mna

[0100] PCT PCTAc Acrylation % Mna(x103Tmc

[0101] (x103%CLa%TMCaD * D *

[0102] (CL:TMC) (CL:TMC) method Acrylationag / mol) (°C) g / mol)

[0103] 70:30 4.0 62 38 1.40 70:30 LDI-HEA 35 4.2 1.41 23

[0104] 75:25 LDI-HEA 51 4.1 1.40 30

[0105] 75'25 3 7 73 27 1 21

[0106] Acryloyl Acryloyl Chloride 76 3.8 1.45 33

[0107] 80:20 3.3 76 24 1.23 80:20 LDI-HEA 44 3.6 1.23 32

[0108] 75:25 6k 5.8 72 28 1.99 75:25 6k LDI-HEA 63 6.2 1.69 22

[0109] 75:25 12k 12.3 72 28 1.58 75:25 12k LDI-HEA 70 12.7 1.66 27aDetermined via1H NMR analysis,bDetermined via GPC in DMF,cDetermined via DSC

[0110] DLP printing

[0111] All resins were processable by DLP. Only PCTAc 75:25 12k structure was soft and sticky, making harder for removing it from the print-head and manipulating it.

[0112] Modulation of shape memory via polymer architecture

[0113] All printed structures were capable to adopt a temporal shape (close box) after programming process and recover their original shape within seconds by putting into a 37 °C water bath. An example of recovering process is shown in Figure 3c, where PCTAc 75:25 box takes 4 seconds for recovering its original shape. The time of shape recovery of the shape-memory articles obtained is shown in Table 2.

[0114] Table 2. Modulation of shape memory via polymer architecture

[0115] Shape

[0116] Variable PCTAc recovery (s)

[0117] Monomer 70:30 2 ratio 75:25 4

[0118] 80:20 6

[0119] End group 75:25 (LDI-HEA) 4

[0120] 75:25 Acryloyl 3 Molecular 75:25 4 kDa 4

[0121] Weight 75:25 6 kDa 2

[0122] 75:25 12 kDa 35

[0123] Mechanical characterization of printed structures

[0124] The thermal mechanical behavior of printed scaffolds were performed by dynamic mechanical analysis (DMA). As shown in Figure 4, the dynamic mechanical properties of the PCT networks depend on the copolymer architecture. All DMA curves exhibited a sharp decrease of the storage modulus (E’) from the rubbery to the melt state around 40 °C, except for PCTAc 6k with a state transition around 20 °C.

[0125] PCTAc 12k was too soft and sticky at room temperature, making impossible to test it by DMA.

Claims

CLAIMS1. Use of a polymer (I) as a precursor of a shape-memory polymer, wherein the polymer (I) comprises a backbone which is end-capped by a crosslinkable end-capping unit comprising a moiety having a crosslinkable functionality, wherein the backbone comprises a copolymer of a cyclic carbonate selected from the group consisting of trimethylene carbonate, ethylene carbonate, propylene carbonate, styrene carbonate and glycerol carbonate and a comonomer selected from the group consisting of E- caprolactone, a-acetolactone, p-propiolactone, y-butyrolactone, 6- valerolactone, p-butyrolactone, y-caprolactone, y-octalactone, y-nonalactone, 6- decalactone, y-decalactone, w-pentadecalactone, diglycolic anhydride, glycolide, lactide, norcamphor lactone, verbanone lactone, dihydrocarvide, wherein the lactone is unsubstituted or substituted by halogen or C1-C12 alkyl, and combinations thereof.

2. Use according to any one of the preceding claims, wherein the weight ratio between the comonomer and trimethylene carbonate is 10:90 to 90:10, more preferably 50:50 to 90:10, more preferably 70:30 to 90:10, more preferably 70:30 to 80:20.

3. Use according to any one of the preceding claims, wherein the polymer (I) or the backbone has Mn of 1.0 to 15 kDa determined by1H-NMR.

4. Use according to any one of the preceding claims, wherein the polymer (I) or the backbone has Mn of 1.0 to 10 kDa determined by1H-NMR.

5. Use according to any one of the preceding claims, wherein the moiety comprising the crosslinkable functionality is selected from the group consisting of (meth)acrylate, (meth)acrylamide, coumarin, (meth)acryloyl, thiol, norbornene, vinyl ether, vinyl ester and combinations thereof.

6. Use according to any one of claims 1-5, wherein the crosslinkable end-capping unit comprises a urethane- and / or urea-containing moiety between the backbone and the moiety comprising the crosslinkable functionality.

7. Use according to claim 6, wherein the urethane- and / or urea-containing moiety is L- lysine diisocyanate ethyl ester.

8. Use according to any one of claims 1-5, wherein the moiety comprising the crosslinkable functionality is directly bonded to the backbone.

9. Use according to claim 8, wherein the polymer (I) is obtained by reacting (meth)acryloyl halide with the backbone.

10. A shape-memory polymer obtained by crosslinking the polymer (I) as defined in any one of claims 1-9.

11. A shape-memory article comprising the shape-memory polymer according to claim 10, wherein the shape-memory article is obtained by a process comprising the steps of: i) providing the polymer (I), ii) forming the polymer (I) into a first article having a first shape, iii) crosslinking the polymer (I) of the first article such that the fist shape is maintained, iv) heating the first article and deforming the first article to obtain a deformed article having a second shape different from the first shape and v) cooling the deformed article such that the second shape is maintained.

12. The shape-memory article according to claim 11 , wherein step ii) comprises the step of mixing the polymer (I) with a photo-initiator and a diluent to obtain a crosslinkable composition and forming the crosslinkable composition into the first article, wherein the diluent is a reactive diluent.

13. The shape-memory article according to claim 11 or 12, wherein the shape-memory article has a switching temperature of 20 to 120 °C.

14. The shape-memory article according to any one of claims 11-13, wherein the shapememory article has a switching temperature of 35 to 55 °C.

15. A drug delivery system, a sensor, a device, stent, or scaffold in support of a minimally invasive procedure or a self-tightening degradable suture, a scaffold for the formation of artificial tissue, self-folding packages, soft robotics, reconfigurable architectures forcell growth, a cell traction force structure, shape memory stent, foldable sheet for cell delivery, shape memory device to treat embolization, staples for wound closure, spinal disk structural reinforcement, comprising the shape-memory article according to any one of claims 11 to 14

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