Photopolymerisable natural oil-based compositions for 4d printing of multifunctional biomaterials

Abstract

The present invention provides a photopolymerisable composition for 4D printing, comprising an acrylated polyol (AOPO) derived from a natural oil, such as olive oil, and acrylic acid as a comonomer. The composition is used in a solvent-free digital light processing (DLR) method to fabricate high-resolution, multifunctional objects. The resulting 4D printed objects are biocompatible, hemocompatible, and cytocompatible. They exhibit excellent temperature- responsive shape memory properties activated near body temperature, inherent antimicrobial activity against both gram-negative and gram-positive bacteria, and tuneable mechanical properties suitable for soft tissue engineering. Furthermore, the composition can be loaded with therapeutic agents, such as progesterone, to form biodegradable objects capable of sustained, controlled drug release. These properties make the material ideal for medical implants, cardiovascular stents, and drug delivery devices.

Description

PH OTOPOLYMERI SABLE NATURAL OIL-BASED COMPOSITIONS FOR 4D PRINTING OF MULTIFUNCTIONAL BIOMATERIALSTECHNICAL FIELD

[0001] The present invention relates generally to the fields of additive manufacturing and 4D printing. More specifically, the invention pertains to a novel photopolymerisable resin derived from natural oil, such as olive oil , and its application in the solvent-free 4D printing of biocompatible materials with multifunctional capabilities, including shape memory, antim icrobial activity, and drug delivery.BACKGROUND

[0002] Additive manufacturing (AM), or 3D printing, has revolutionised the production of complex components across a wide range of materials, including metals, ceramics, and polymers. Its inherent advantages, such as unrestricted design freedom, streamlined manufacturing, and material efficiency, have made it a key technology in high-value domains like soft robotics, electronics, and tissue engineering. Within the AM market, photopolymer resins are dominant, valued for their st rang mechanical, chemical, and thermal stability, as well as their high printing resolution. Digital light processing (DLP), a specific 3D printing technique, uses liquid photopolymer resins to create crosslinked materials with excellent durability and mechanical properties.

[0003] However, the majority of these commercial resins are derived from fossil-based sources, which raises concerns about cost and environmental sustainability. This has created a pressing need for renewable and environmentally friendly alternatives to meet the growing demand for AM materials. Natural oils, such as olive oil, present a promising renewable resource. Olive oil is not only a staple in cooking but is also used for medicinal and cosmetic purposes. It is known to possess numerous health benefits, including anti-inflammatory, antioxidant, and antibacterial properties. Furthermore, studies have shown that its primary component, oleic acid (OA), can promote wound healing and may serve as a growth factor in tissue engineering by positively influencing cell proliferation and differentiation.

[0004] Building on 3D printing, four-dimensional (4D) printing has emerged as a transformative technology. 4D printing creates objects that can dynamically change their shape, properties, or function in response to external stimuli like heat, light, or moisture. Thiscapability is of great interest in the biomedical field for applications such as smart medical devices, flexible bioelectronics, and tissue engineering. Temperature-responsive 4D printed polymers are particularly attractive, as they can be programmed to recover their original shape when heated to near body temperature, making them ideal for minimally invasive surgical procedures.

[0005] Despite this potential, existing 4D printing materials face several significant limitations:■ Fossil fuel dependence: Many resins are derived from non-renewable petroleum sources, posing environmental concerns.■ Limited biocompatibility: Some materials may be toxic or cause adverse immune responses, making them unsuitable for long-term biomedical use.■ High transition temperatures: Many shape memory polymers require activation temperatures that are too high for practical biomedical applications, which need to function at or near body temperature.■ Synthesis challenges: The production of biocompatible shape memory polymers often involves complex processes, toxic catalysts, or harmful solvents.■ Low resolution: Existing methods for creating shape memory constructs often lack the high precision offered by light-based techniques like DLP.

[0006] The present invention addresses these challenges by introducing a novel photoresin derived from olive oil, specifically designed for high-resolution, solvent-free 4D printing. This approach leverages a renewable resource to create materials with excellent biocompatibility, tuneable mechanical properties, and smart, temperature-responsive shape memory capabilities, offering a sustainable and high-performance alternative to conventional photoresins.BRIEF DESCRIPTION OF DRAWINGSFIG. 1 Ashows the synthesis route of the olive oil-derived acrylated polyol (AOPO) photocurable resin; and FIG. 1 B shows the visual transformation of the material during each step of the reaction.FIGs. 2A-2C present spectroscopic analysis confirming the synthesis, including: the FTIR spectra (FIG. 2A) of olive oil (OO), epoxidised olive oil (EOO), and AOPO; a magnified view of thefingerprint region of the FTIR spectra (FIG. 2B); and a1H NMR spectra of 00, EOO, and AOPO (FIG.2C).FIG. 3 provides a schematic illustration of a DLP 3D printer and photographs of various objects printed from the developed resins.FIGs. 4A-4E display the physicochemical properties of the 4 D printed polymers, including: FTIR spectra (FIG. 4A); TGA and DTG spectra (FIG. 4B); DSC spectra FIG. 4C; in vitro hydrolytic degradation profiles (FIG. 4D); and aschematic illustration of the polymeric structure (FIG. 4E). FIGs. 5A-5O illustrate the compressive mechanical properties of the 4D printed polymers, including stress-strain curves, cyclic loading experiments, and fatigue tests.FIGs. 6A-6F demonstrate the temperature-responsive shape memory performance of the 4D printed polymers, showing a schematic representation of the shape memory evaluation (FIG. 6A); the fixity ratio (FIG. 6B); the recovery ratio (FIG. 6C); and digital photographs of the shape recovery process for various printed objects, including strips and a stent (FIGs. 6D-6F).FIGs. 7A-7F present the biocompatibility of the 4D printed polymers, showing an Alamar blue cell viability assay (FIG. 7A); a blood compatibility (haemolysis) assay (FIG. 7B); and fluorescent and cellular morphology images of NIH / 3T3 cells after 1 and 3 days of exposure to conditioned media (FIGs. 7C-7F).FIGs. 8A-8F show the antibacterial performance of the 4D printed polymers against gramnegative E coli and gram-positive B. subtilis, including growth kinetics (FIGs. 8A and 8B, respectively), live / dead fluorescence imaging (FIGs. 8C and 8D, respectively), and SEM imaging (FIGs. 8Eand 8F, respectively).FIGs. 9A-9C illustrate the preparation of the working curve for the photocurable resins, showing the CAD model used (FIG. 9A); the resulting printed model (FIG. 9B); and the semi-log (FIG. 9C) working curve for three different resin compositions.FIGs. 10A-10D detail the systematic precision test to determine the printing resolution, includingthe CAD design model (FIG. 10A); a microscope image of the printed model (FIG. 10B); and graphs showing the printing accuracy for pillar width (FIG. 10C) and pillar height (FIG. 10D). FIGs. 11A-11 E show the tensile properties of the printed polymers, including a typical stressstrain curve and bar graphs (FIG. 11 A) for maximum tensile strength (FIG. 11 B), elongation at break (FIG. 11 C), toughness (FIG. 11 D), and Young's modulus (FIG. 11 E).FIGs. 12A-12C show the recovery properties of the printed polymers after 2 min. of resting following 20% compressive strain for P(AOPO) (FIG. 12A), P(AOPO)-10AA (FIG. 12B), and P(AOPO)-25AA(FIG. 12C).FIG. 13A demonstrates a microscope image of a progesterone crystal ; FIG. 13B shows the crystal embedded within a printed polymer disc; and FIGs. 13C-13D show the subsequent controlled, sustained release of progesterone from the matrix over 24 hours.SUMMARY OF THE INVENTION

[0007] The present invention relates to a novel photopolymerisable composition derived from natural oil, formulated for high-resolution, solvent-free 4D printing of multifunctional biocompatible materials. The composition enables the fabrication of objects with a unique combination of properties, including temperature-responsive shape memory, inherent antimicrobial activity, and the capacity for controlled drug delivery.

[0008] In a first aspect, the present invention provides a photopolymerisable composition comprising an acrylated polyol (AOPO) derived from a natural oil ; and acrylic acid (AA) as a diluent and comonomer. In one embodiment, the composition further comprises at least one active agent. In a specific embodiment, the active agent is a therapeutic agent, such as progesterone. In certain embodiments, the active agent is in a crystalline form. In another embodiment, the natural oil is selected from the group consisting of olive oil, soybean oil, canola oil, sunflower oil, sesame oil, linseed oil, safflower oil, peanut oil, corn oil, walnut oil, and grapeseed oil.

[0009] In a further embodiment, the composition further comprises a photoinitiator. In a particular embodiment, the composition comprises 75-100 wt% of an acrylated polyol (AOPO) derived from olive oil ; 0-25 wt% of acrylic acid (AA); and 0.5-3 wt% of a photoinitiator, wherein the weight percentages of the photoinitiator are based on the total weight of AOPO and AA. Preferably, the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide. In yet another embodiment, the acrylated polyol is synthesised from the natural oil via a two-stage process. This process comprises a first stage of epoxidation of the natural oil and a second stage of ring-opening of the epoxidised natural oil with 2- hydroxyethyl acrylate.

[0010] In a second aspect, the present invention provides a 4D printed object formed from the photopolymerisable composition of the first aspect. In one embodiment of the second aspect, the object exhibits temperature-responsive shape memory properties. The shapememory properties may be activated with a transition temperature near human body temperature. In another embodiment, the object exhibits antimicrobial properties, for instance against both gram-negative and gram-positive bacteria. In a further embodiment, the object is biocompatible, hemocompatible, and / or cytocompatible. In still another embodiment, the object has mechanical properties similar to at least one soft tissue selected from the group consisting of ligaments, aorta, articular cartilage, and soft collagenous bone. In a specific embodiment, the object is configured for the controlled release of at least one active agent.

[0011] In a third aspect, the present invention provides a method of 4D printing an object, comprising: providing the photopolymerisable composition of the first aspect; depositing the composition layer-by-layer according to a digital design using a digital light processing (DLP) 3D printer; and photopolymerising each deposited layer to form the object. In one embodiment of the method, each deposited layer is photopolymerised to achieve a z-resolution of 50 pm or less, preferably about 20 pm. In another embodiment of the method, wherein the photopolymerisable composition includes at least one active agent, the step of providing the composition comprises mixing the active agent into the composition prior to the depositing step.

[0012] In afourth aspect, the present invention provides a4D printed object accordingto the second aspect for use in a medical application. In one embodiment of the fourth aspect, the medical application is selected from the group consisting of a medical implant, a temporary antim icrobial dental filling, a drug delivery device, an orthopaedic biodegradable screw, a cardiovascular application such as a biodegradable stent, an antimicrobial soft catheter for urological applications, and a nerve conduit for nerve regeneration. In a particular embodiment, the object is for use as a biodegradable long-term drug delivery device.DETAILED DESCRIPTION OF THE INVENTION

[0013] In the following description, various aspects of the present invention will be described. For purposes of explanation, specific details are set forth in order to provide a thorough understanding of the present invention. However, it will also be apparent to one skilled in the art that the present invention may be practiced without the specific details presented herein. Furthermore, well-known features may be omitted or simplified in order not to obscure the present invention.

[0014] The term “comprising”, used in the claims, is “open ended” and means the elements recited, or their equivalent in structure or function, plus any other element or elements which are not recited. It should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It needs to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. Thus, the scope of the expression “a composition comprising x and z” should not be limited to compositions consisting only of components x and z. Also, the scope of the expression “a method comprisi ng the steps xand z” should not be limited to methods consisting only of these steps.

[0015] Unless specifically stated, as used herein, the terms “about” and “approximately” are understood as within a range of normal tolerance in the art, for example within two standard deviations of the mean. In one embodiment, the term “about” means within 10% of the reported numerical value of the number with which it is being used, preferably within 5% of the reported numerical value. For example, the term “about” can be immediately understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1 %, 0.5%, 0.1 %, 0.05%, or 0.01 % of the stated val ue. In other embodiments, the term “about” can mean a higher tolerance of variation depending on for instance the experimental technique used. Said variations of a specified value are understood by the skilled person and are within the context of the present invention. As an illustration, a numerical range of “about 1 to about 5” should be interpreted to include not only the explicitly recited values of about 1 to about 5, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4 and sub-ranges, for example from 1-3, from 2-4, and from 3-5, as well as 1 , 2, 3, 4, 5, or 6, individually. This same principle applies to ranges reciting only one numerical value as a minimum or a maximum. Unless otherwise clear from context, all numerical values provided herein are modified by the term "about". Other similar terms, such as “substantially”, “generally”, “up to” and the like are to be construed as modifying a term or value such that it is not an absolute. Such terms will be defined by the circumstances and the terms that they modify as those terms are understood by those of skilled in the art. This includes, at very least, the degree of expected experimental error, technical error and instrumental error for a given experiment, technique or an instrument used to measure a value.

[0016] As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items. Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that isconsistentwith their meaning in the context of the specification and relevant art and should not be interpreted in an idealised or overly formal sense unless expressly so defined herein. Well-known functions or constructions may not be described in detail for brevity and / or clarity.

[0017] As used herein, a “ photopolymerisable composition” refers to a liquid formulation, often called a resin, that undergoes polymerisation to form a solid material upon exposure to light, typically in the ultraviolet (UV) range. In the context of the present invention, this composition comprises an acrylated polyol, acrylic acid, and a photoinitiator, and is formulated for use in 4D printing systems.

[0018] The term “acrylated polyol (AOPO)” refers to a polymer synthesised from a natural oil, which is characterised by the presence of both acrylate functional groups and multiple hydroxyl (-OH) groups (polyol). The acrylate groups enable photopolymerisation, while the polyol structure contributes to the final network and properties of the printed material. Specifically, the AOPO of the present invention is synthesised through epoxidation of a natural oil followed by a ring-opening reaction with 2-hydroxyethyl acrylate.

[0019] A“ natural oil” refers to a triglyceride derived from a plant source. These oils consist of fatty acid chains, many of which contain carbon-carbon double bonds that can be chemically modified for polymerisation. As used herein, natural oil includes, but is not limited to, olive oil, soybean oil, canola oil, sunflower oil, sesame oil, linseed oil, safflower oil, peanut oil, corn oil, walnut oil, and grapeseed oil.

[0020] A “diluent” is a substance added to a composition to reduce its viscosity. In the present invention, acrylic acid acts as a reactive diluent, lowering the viscosity of the AOPO to a level suitable for high-resolution DLP printing without the need for non-reactive solvents. A “comonomer” is a monomer that polymerises together with at least one other type of monomer to form a copolymer. Acrylic acid serves as a comonomer with AOPO, allowing for the tuning of physicochemical properties such as mechanical strength, thermal properties, and degradation rate of the final printed object.

[0021] An “active agent” is a substance intended to impart a specific activity or effect. As used herein, this term includes therapeutic agents. A “therapeutic agent” is a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. The present invention demonstrates the incorporation of progesterone as a therapeutic agent. “Crystalline form” refers to the solid state of a substance in which its constituent atoms, molecules, or ions are arranged in a highly ordered, repeating three-dimensional pattern. In one embodiment of the invention, an active agent such as progesterone is incorporated into the photopolymerisable composition in its crystalline form. A “photoinitiator” is a chemical compound that, upon absorbing light energy, generates reactive species (such as free radicals) that initiate a polymerisation reaction. In this invention, diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO) is a preferred photoinitiator.

[0022] “4D printing” refers to an additive manufacturing process that fabricates three- dimensional objects which are programmed to change their shape, properties, or function over time in response to an external stimulus. The fourth dimension is time. The objects of the present invention are capable of such changes, particularly in response to temperature.

[0023] “Temperature-responsive shape memory” is a property of a material that allows it to be deformed from its original (permanent) shape into a temporary, fixed shape, and then to recover its permanent shape upon exposure to a suitable temperature stimulus. The 4D printed objects of this invention exhibit this property, with shape recovery being triggered at or near human body temperature (e.g., 37°C). The “transition temperature” is the temperature at which a shape memory polymer undergoes a phase transition that enables shape recovery. For the amorphous crosslinked polymers of this invention, the glass transition temperature (7^) serves as the transition temperature.

[0024] “Biocompatible” refers to the ability of a material to perform its desired function without eliciting any undesirable local or systemic effects in the host. As used herein, it encompasses cytocompatibility and hemocompatibility. “Cytocompatible” means the material is not toxic to cells. The printed polymers of the invention are considered cytocompatible, as demonstrated by high cell viability (>80% after 3 days) in NIH / 3T3 fibroblasts. “ Hemocompatible” means the material is compatible with blood and does not induce significant haemolysis or thrombosis. The printed polymers of the invention are considered hemocompatible, exhibiting a haemolysis index below 1 %.

[0025] “Controlled release” refers to the delivery of an active agent from a system over a sustained period, rather than in an immediate, single burst. The 4D printed objects of the invention, when loaded with an active agent like progesterone, demonstrate the ability to release the agent cumulatively over time, making them suitable as drug delivery devices.

[0026] “ Digital light processing (DLP)” is a vat photopolymerisation additive manufacturing technology that employs a digital projector to cure an entire layer of liquid photopolymer resin simultaneously. “Z-resolution” refers to the minimum achievable layer thickness in the vertical (z-axis) direction of a printed object. The methods and compositions of the present invention are capable of achieving a high z-resolution of about 20 pm .

[0027] In a primary aspect, the invention provides a photopolymerisable composition, or resin, designed for additive manufacturing. This composition comprises as its main components an acrylated polyol (AOPO) derived from a natural oil, and acrylic acid (AA), which serves a dual role as a reactive diluent and a comonomer.

[0028] The AOPO is the primary polymerisable component of the resin. It is synthesised from a natural oil, which is a renewable and sustainable resource. In a preferred embodiment, the natural oil is olive oil. However, other natural oils containing unsaturated fatty acids suitable for chemical modification can also be used, including but not limited to, soybean oil, canola oil, sunflower oil, sesame oil, linseed oil, safflower oil, peanut oil, corn oil, walnut oil, and grapeseed oil. The suitability of these oils stems from their content of monounsaturated and / or polyunsaturated fatty acids, which contain the carbon-carbon double bonds necessary for the epoxidation step of the synthesis. The typical fatty acid compositions of these oils are presented in the following table:

[0029] The synthesis of AOPO is achieved through a straightforward and eco-friendly two- stage process, as illustrated in FIG. 1 A. The first stage involves the epoxidation of the carboncarbon double bonds present in the fatty acid chains of the natural oil. This is followed by a second stage involving a ring-opening reaction of the newly formed epoxide groups with 2- hydroxyethyl acrylate (HEA). This second step grafts the polymerisable acrylate groups onto the oil backbone and simultaneously generates hydroxyl groups, thereby forming the acrylated polyol structure. FIG. 1 B shows the visual transformation from golden yellow olive oil to a transparent faint yellow epoxidised olive oil, and finally to the brown, viscous AOPO resin, indicating successful chemical modification at each step. The structure of the synthesised materials isconfirmed by spectroscopic methods, with FIG. 2Ashowingthe representative FTIR spectra, which track the disappearance of double bonds (peak at 3006 cm-1) and the appearance of epoxide groups (peak at 827 cm-1) and, subsequently, broad hydroxyl bands (3600-3200 cm-1) and acrylate-related peaks (1636 cm-1).

[0030] A key component of the composition is acrylic acid (AA). AA functions as a reactive diluent, significantly reducing the viscosity of the AOPO resin to a range suitable for high- resolution DLP printing without requiring non-reactive, volatile solvents. Furthermore, AA acts as acomonomerthat copolymerises with the AOPO during photopolymerisation. By varyingthe weight percentage of AA in the formulation, typically from 0 wt% to 25 wt%, it is possible to precisely tune the physicochemical properties of the final printed object. This includes adjusting the mechanical strength, thermal properties (e.g., glass transition temperature), hydrophilicity, and biodegradation rate of the material .

[0031] To initiate polymerisation upon exposure to light, the composition further comprises a photoinitiator. In some embodiments, the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO), used in a concentration of about 0.5 wt% to 3 wt% based on the total weight of the AOPO and AA monomers. In certain embodiments, the photopolymerisable composition is formulated to serve as a matrix for the delivery of an active agent. The active agent can be any substance intended to impart a biological or therapeutic effect. In a specific embodiment, the active agent is a therapeutic agent, such as the hormone progesterone. The active agent may be incorporated into the resin prior to printing, for example, in its crystalline form. FIGs. 13A-13B demonstrate this capability, showing a progesterone crystal embedded within a printed polymer disc; and FIGs. 13C-13D show the subsequent controlled, sustained release of progesterone from the matrix over 24 hours.

[0032] In another aspect, the invention provides a 4D printed object fabricated from the photopolymerisable composition described above. These objects are not static; they possess multifunctional properties and can respond to external stimuli, qualifying them as “smart” materials. Aprimary characteristic of the printed objects is their temperature-responsive shape memory capability. As illustrated schematically in FIG. 6A, an object can be deformed from its permanent, printed shape into atemporary shape (e.g., bent ortwisted) and “fixed” in this state by cooling. Upon reheating to a transition temperature, the object automatically recovers its original , permanent shape.

[0033] Forthe polymers of this invention, the transition temperature is governed by their glass transition temperature (Tg), which is tunable via the resin composition to be near human body temperature (37°C), making them ideal for biomedical applications. Reference is now made to FIGs. 6D and 6E providing visual evidence of this property, showing a printed strip recovering from ‘ U’ and twisted shapes in 37°C water. FIG. 6F further demonstrates the potential of this technology with a printed stent recovering its open shape, a critical function for minimally invasive deployment. The fixity and recovery ratios, shown in FIGs. 6B and 6C, are excellent, with fixity reaching nearly 100% for the P(AOPO)-25AAformulation.

[0034] The printed objects also exhibit potent intrinsic antimicrobial properties. This is a significant advantage for medical implants, as it can help prevent device- associated infections. As shown in FIGs. 8A-8F, the materials demonst rate complete killing of both gram -negative (E. coli) and gram-positive (B. subtilis) bacteria upon direct contact. This is evidenced by the flat growth kinetics curves and clear agar plates (FIGs. 8Aand 8B), fluorescence (FIGs. 8C and 8D), and SEM images (FIGs. 8E and 8F) showing widespread bacterial cell death and membrane rupture, in stark contrast to the healthy control bacteria. This antibacterial activity is attributed to the olive oil base of the polymer.

[0035] Furthermore, the objects are exceptionally biocompatible. FIGs. 7A-7F present comprehensive data supporting this claim. Quantitative Alamar blue assays show high cell viability (over 80% after 3 days) when NIH / 3T3 fibroblast cells are exposed to the material's degradation products (FIG. 7A). This is corroborated by live / dead staining, which shows a vast majority of live (green) cells and healthy, spread morphology, similar to controls (FIGs. 7C-7F). The materials are also highly hemocompatible, with a haemolysis assay showing a haemolysis index below 1 %, well within the safe range for blood-contacting devices (FIG. 7B).

[0036] The mechanical properties of the printed objects are highly tuneable by adjusting the AA content in the resin. As detailed in FIGs. 11A-11 E (tensile properties) and FIGs. 5A-5O (compressive properties), increasing the AA content significantly enhances tensile strength, elongation at break, and toughness. For example, the tensile strength increases nearly sevenfold from P(AOPO) to P(AOPO)-25AA. This tunability allows the material’s mechanical profile to be matched to that of various soft tissues, such as ligaments, aorta, articular cartilage, and soft collagenous bone, making it suitable for a wide range of tissue engineering applications. The materials also show excellent fatigue resistance and recovery after deformation, as seen in the cyclic loading tests presented in FIGs. 5A-50 and FIGs. 12A-12C.

[0037] Another aspect of the invention is the method for fabricating these multi-functional objects. The method utilises digital light processing (DLP) 3D printing, a vat photopolymerisation technique known for its speed and precision. Aschematic of atypical DLP printer is shown in FIG. 3A. The process involves depositing the liquid photopolymerisable composition layer-by-layer and curing each layer with a pattern of UV light projected by a digital micromirror device.

[0038] Akey advantage of the present invention is the ability to achieve high-resolution prints. The formulation's optimised curing kinetics, determined from working curves as shown in FIGs. 9A-9C, enable the printing of fine features and intricate geometries. The method can achieve a z-resolution (layer thickness) of 50 pm or less, and even as low as 20 pm, as demonstrated in FIG. 3 by the magnified images (d) and (I) of a printed cube. FIG. 3 showcases a variety of complex objects printed with high fidelity, such as gyroids, pyramids, theTechnion logo in image (h), and biomedical stents. The printing accuracy is systematically verified in FIGs. 10A-10D, which show that printed pillar widths and heights closely match the digital CAD design, even for features as small as 90 pm. The entire printing process is performed without the use of any non- reactive solvents, contributing to its environmental and operational safety.

[0039] When fabricating objects for drug delivery, the active agent is incorporated by simply mixing it into the liquid resin prior to printing, ensuring its distribution throughout the final polymer matrix.

[0040] Given their unique combination of properties, the 4D printed objects of the present invention are suitable for numerous applications, particularly in the biomedical field. Nonlimiting examples of these applications are creatng medical implants that are biocompatible, biodegradable, and possess inherent antimicrobial properties to reduce infection risk. Theshape memory effect is particularly useful for minimally invasive devices. For example, a cardiovascular stent can be printed, compressed into a temporary shape for catheter-based delivery, and then expanded to its functional shape inside a blood vessel upon warming to body temperature.

[0041] The material’s tuneable mechanical properties make it an excellent candidate for soft tissue engineering scaffolds, where the scaffold's stiffness can be matched to the target tissue (e.g., cartilage, ligament) to promote proper cell growth and tissue regeneration. The ability to i ncorporate and release active agents al lows the objects to function as biodegradabl e long-term drug delivery devices, releasing therapeutics locally over an extended period. Other potential applications include, but are not limited to, temporary antimicrobial dental fillings, orthopaedic biodegradable screws, antimicrobial soft catheters, and nerve conduits for nerve regeneration.EXAMPLES

[0042] The following examples are provided to further illustrate the invention and are not intended to be limiting.Materials and Methods

[0043] Commercial olive oil (OO) (iodine value ~80.44±1 .33 g / 100 g) was purchased from a local supermarket. Formic acid (HCOOH), sulfuric acid (H2SO4), hydrogen peroxide (H2O2), and acrylic acid (AA) were obtained from Merck, Israel . Dichloromethane and isopropanol were purchased from Biolab, Israel . 2-Hydroxyethyl acrylate (HEA), hydroquinone (HQ), and chloroform-d (CDCI3) were purchased from Sigma Aldrich. Diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO) was purchased from TCI Chemicals. Cell culture reagents, including DMEM, foetal bovine serum (FBS), and antibiotics, were purchased from ThermoFisher Scientific and Sigma-Aldrich. NIH / 3T3 cells, E coli (MG1566), and B. subtilis (W168) were obtained from internal collaborators at theTechnion. Progesterone wasdissolved in acetonitrile (ACN) for crystallisation. All characterisation instruments, including FTIR, NMR, TGA, DSC, and mechanical testers, were standard laboratory equipment.Example 1 : Synthesis and Characterisation of Acrylated Polyol (AOPO)

[0044] The acrylated polyol (AOPO) resin was prepared via a two-step synthetic process as depicted in FIG. 1 A. The reactants involved in this synthesis are shown below.Step 1 : Epoxidation of Olive OH (OO)

[0045] Epoxidised olive oil (EOO) was prepared by reacting olive oil with in situ generated performic acid. Specifically, 200 g of olive oil and 22 mL of glacial formic acid were placed in a round-bottom flask at 55 °C. After adding 1 mL of concentrated H2SO4as a catalyst, 162 mL of 30% hydrogen peroxide was added dropwise over 1 hour. The reaction proceeded overnight at 55 °C. The resulting mixture was washed repeatedly with distilled water until a pH of -6.5 was reached. Rotary evaporation was used to remove residual water, yielding a transparent, faintyellow EOO with a yield of -70%.

[0046] The successful conversion was confirmed by spectroscopy. In the FTIR spectrum of the original olive oil (FIG. 2A), characteristic peaks are observed at 2920 and 2853 cm-1(asymmetric and symmetric stretching of aliphatic -CH2-groups), 1744 cm-1(carbonyl -C=O- groups), and 3006 cm-1(C-H stretching of -CH=CH-). Upon epoxidation, the FTIR spectrum showed the complete disappearance of the C-H stretching peak of -CH=CH-at 3006 cm-1and the appearance of a new peak at 827 cm-1corresponding to the epoxide group (FIG. 2B).Characterisation data for EOO:

[0047] 1H NMR(400 MHz, CDCI3): 55.25 (m, 1 H, -CH-O-CO-), 4.29-4.11 (m, 4H, -CH2-O-CO- ), 2.86 (m, epoxy protons), 2.30 (t, J= 7.5 Hz, 6H, -CH2-COO-), 2.01 (m, 6H, -CH2-CH=), 1 .62 (m , 6H, -CH2-), 1 .30 (s, aliphatic protons), 0.88 (t, J=6.8 Hz, 9H, -CH3). The peak for olefinic protons at 5 5.35 ppm disappeared, and a new peak corresponding to hydrogens on the epoxy group appeared at 52.86 ppm . The complete disappearance of the olefinic proton peak at 55.35 ppm confirmed 100% epoxidation.

[0048] 13C NMR (100 MHz, CDCI3): 5 173.2, 172.8 (-COO-), 68.9 (-CH-O-), 62.1 (-CH2-O-), 57.0 (epoxide carbons), 34.2, 34.0, 31 .9, 29.7, 29.5, 29.3, 29.1 , 27.2, 25.6, 24.9, 22.7 (aliphatic carbons), 14.1 (-CH3). The peak for unsaturated carbons at 5 130 ppm disappeared, and a new peak for carbons of the epoxide group appeared at 557 ppm.

[0049] ESI-MS: m / z calculated for C57H104O9[M+Na]+971.75, found major peaks corresponding to different fatty acid compositions, including 908.90, 922.88, 936.86, and a base peak at 950.91 [M+Na]+for triolein with three epoxidations. EOO showed an molecular weight with a representative peak at m / z 950.91 , an increase from the starting olive oil (representative peak at m / z 902.97), confirming the addition of oxygen atoms.Step 2: Synthesis of Acryiated Polyol (AOPO)

[0050] The acryiated polyol was prepared via an oxirane ring-opening reaction of EOO with HEA. In a typical procedure, 20 g of EOO, 5 g of HEA, and 0.1 g of hydroquinone (HQ) inhibitor were stirred at 105 °C for 26 hours under reflux. The reaction progress, monitored by1H NMR, was accompanied by a colour change from faint yellow to brown and an increase in viscosity, as seen in FIG. 1 B. Unreacted HEA was removed by washing with a dichloromethane / water mixture. The final product was dried under reduced pressure to yield AOPO (-63% yield). The successful acrylation was confirmed by spectroscopy. The FTIRspectrum (FIG. 2A) showed the appearance of a broad -OH stretching peak between 3600-3200 cm-1, a C=C stretching vibration at 1636 cm-1, and bending vibrations for =CH2at 1407 and 984 cm-1, indicating the successful incorporation of acrylate groups.Characterisation data for AOPO:

[0051] 1H NMR (400 MHz, CDCI3): 5 6.40 (d, J= 17.3 Hz, 1.8H, =CH2), 6.14 (dd, J= 17.3, 10.4 Hz, 1.8H, -CH=), 5.85 (d, J= 10.4 Hz, 1.8H, =CH2), 5.25 (m , 1 H, -CH-O-CO-), 4.29-4.11 (m , includes -CH2-O-CO- and -O-CH2-CH2-O- from acrylate), 3.83 (m , includes -CH(OH)- and -O- CH2-CH2-O-), 2.30 (t, J= 7.5 Hz, 6H, -CH2-COO-), 1 .62 (m), 1 .30 (s, aliphatic protons), 0.88 (t, J = 6.8 Hz, 9H, -CH3). The peak for epoxy hydrogens at 52.86 ppm diminished completely, while new peaks for acrylic protons appeared at 56.40, 6.14, and 5.85 ppm. Methylene protons in the acrylate portion appeared at 54.26 and 3.83 ppm. The average number of acrylate groups per oil molecule was calculated to be -1 .8 based on the integration ratio of acrylic protons to the terminal methyl protons.

[0052] 13C NMR (100 MHz, CDCI3): 5 173.2, 172.8 (-COO-), 166.2 (-O-CO-CH=, acrylate), 131.0 (=CH2), 128.0 (-CH=), 71.8 (-CH(OH)-), 68.9 (-CH-O-), 63.6, 62.1 (-CH2-O-), 34.2-22.7 (aliphatic carbons), 14.1 (-CH3). New peaks at 5 131 and 128 ppm confirmed the presence of acrylic carbons.

[0053] ESI-MS: m / z showed a distribution corresponding to the addition of HEA units. A representative base peak was observed at 1024.95, along with other major peaks at 908.89, 950.91 , 1066.97, and 1141 .01 , confirming the successful ring-opening and acrylation reaction. AOPO showed a further increase in average molecular weight, with a representative peak at m / z 1024.95, consistent with the addition of HEA molecules.Example 2: Preparation and Curing Characterisation of Photoresins

[0054] Three different resin formulationswere prepared by mixingthesynthesised AOPOwith acrylic acid (AA) and 3 wt% TPO photoinitiator. Their compositions and physical properties are detailed in Table 1A. The corresponding double bond conversion, gel content and swelling percentage of 4D printed polymers are summarised in Table 1 B.Table 1 A: Resin compositions and properties.Table 1 B: Double bond conversion, gel content and swelling of 4D printed polymers.

[0055] The curing characteristics of each resin were determined by preparing Jacobs' working curves using a DLP 3D printer. A CAD model with 20 squares of increasing thickness was designed (FIG. 9A) and printed (FIG. 9B). The cured thickness of each square was plotted against the corresponding UV energy dose to generate a semi-log working curve (FIG. 9C). From these curves, the critical energy (Ec, the minimum energy to initiate polymerisation) and penetration depth (Dp, a measure of how deep light penetrates the resin) were calculated. As shown in Table 1A, the addition of AA as a reactive diluent drastically reduced the viscosity of the resin, from 1025 cP for pure AOPO to 324 cP for AOPO-25AA. This also resulted in a nearly nine-fold reduction in the critical energy required for curing, which significantly speeds up the printing process.Example 3: 4D Printing and Resolution Assessment

[0056] Reference is made to FIG. 3 demonstrating various objects printed from the three resin formulations using an Asiga Max X DLP 3D printer schematically shown in image (a). CAD files were prepared in SolidWorks software. After printing, samples were washed withisopropanol to remove unreacted resin and post-cured with UV light. The versatility of the resins enabled the printing of awide range of structures with high fidelity, from simple cubes in image (d) and pyramids in image (f) to complex gyroids in images (b-c), hollow discs in image (g), a detailed Technion logo in image (h), and biomedical devices like stents in image (m) and a rook in image (n). The printer achieved a high z-resolution, with layer thicknesses as low as 20 pm clearly visible under a microscope as seen in image (I).

[0057] Specifically, image (d) shows 4D printed cube using AOPO. Image (e) shows the magnified image of each layer of this cube. Image (f) shows the 4D printed pyramid using the acrylated polyol (AOPO), and image (g) shows the 4D printed circular disc using the same polymer. Images (h-i) show the 4D printed top and side views of Technion logo using the AOPO- 10AA polymer. Image (j) shows the 4D printed flower using AOPO-25AA, and image (k) shows the 4D printed high-resolution pyramid using AOPO-25AA. Images (m-n) shows the printed stent and rook using the AOPO-25AA polymer.

[0058] To quantify the printing precision, a test model with an array of pil lars of varying widths (from 90 pm to 900 pm) and a constant height (300 pm) was designed (FIG. 10A) and printed (FIG. 10B). Measurements of the printed features, shown in FIGs. 10C and 10D, revealed excellent accuracy. The printed pillar widths showed near- zero deviation from the CAD design for all resins, and the pillar heights had a maximum inconsistency of only ~10 pm, confirming the high resolution of the printing process.Example 4: Physicochemical Properties of 4D Printed Polymers

[0059] FTIR Analysis: The printed polymers are designated P(AOPO), P(AOPO)-10AA, and P(AOPO)-25AA. FTIR spectra of the printed polymers (FIG. 4A) confirmed the successful photopolymerisation through the complete disappearance of the C=C peak at 1636 cm-1. The spectra for all printed polymers showed a broad peak between 3600-3200 cm-1for hydrogen- bonded hydroxyl groups and a peak around 1735 cm-1for ester bonds. For P(AOPO)-10AA and P(AOPO)-25AA, the latter peak is a combination of ester and carboxylic acid groups. Quantitative analysis showed a high degree of double bond conversion : -97.0% for P(AOPO), -81.0% for P(AOPO)-10AA, and -84.0% for P(AOPO)-25AA, confirming efficient photopolymerisation.

[0060] Gel Content and Swelling: The degree of crosslinking was investigated by measuring the gel content (insoluble fraction) and swelling percentage in isopropanol. P(AOPO) exhibitedthe highest gel content (74.67 ± 1.75%) and the lowest swelling (15.12 ± 0.51%). In contrast, P(AOPO)-25AA showed the lowest gel content (56.23 ± 2.41 %) and the highest swelling (76.31 ± 3.72%). This indicates that P(AOPO) has a high degree of permanent, chemical crosslinking, while the addition of AA leads to a network with fewer chemical crosslinks but more flexibility and capacity to absorb solvent, likely due to physical interactions like hydrogen bonding.

[0061] Thermal Stability (TGA): Thermogravimetric analysis was performed to evaluate the thermal stability of the printed polymers, with the results (TGAcurves) displayed in FIG. 4B. All formulations were found to be stable up to 150 °C, after which degradation began. P(AOPO) exhibited the highest thermal stability, which is attributed to its higher crosslinking density compared to the other formulations. In the case of P(AOPO), each AOPO molecule can crosslink with another, whereas the introduction of AA repl aces some AOPO molecules, thereby reducing the overall degree of chemical crosslinking and, consequently, the thermal stability.

[0062] Thus, the thermal stability decreased as the acrylic acid content increased, with P(AOPO)-25AA showing the fastest degradation. At 400 °C, the weight loss was approximately 10% for P(AOPO), 15% for P(AOPO)-10AA, and 20% for P(AOPO)-25AA. Asignificant weight loss event occurred for all polymers beyond 400 °C, with about 90% of the initial weight being lost by 500 °C. The differential thermal gravimetry (DTG) curve showed that the maximum weight loss for all samples occurred in a single stage at approximately 435 °C.

[0063] Thermal Transitions (DSC): DSC thermograms (FIG. 4C) showed no distinct melting point, indicating the polymers are amorphous and cross-linked. All polymers exhibited two distinct glass transition temperatures (Tg), which arise from the presence of soft and hard domains within the polymer structure. The lower Tgl(4.5-9.2 °C) is attributed to the molecular motion of soft aliphatic segments of the triglyceride structure, while the higher Tg2(19.8-25.5 °C) corresponds to the relaxation of the hard, crosslinked domains. The values were found: P(AOPO): Tgl= 9.2 °C, Tg2= 25.5 °C; P(AOPO)-10AA: Tgl= 6.9 °C, Tg2= 22 °C; and P(AOPO)- 25AA: Tgl= 4.5 °C, Tg2= 19.8 °C. Both Tgvalues decreased with increasing AAcontent, which is attributed to the increased flexibility of the polymer network.

[0064] Hydrolytic Degradation: The in vitro hydrolytic degradation profiles in PBS (pH 7.4) are shown in FIG. 4D. All polymers exhibited a slow degradation profile due to the hydrophobic nature of the oil backbone. The degradation primarily occurs through the cleavage of ester bonds. P(AOPO) showed the slowest degradation (~5% mass loss in 28 days) due to itshydrophobicity. The degradation rate increased with AA content. P(AOPO)-1 OAA and P(AOPO)- 25AA exhibited ~11%and -13% mass loss (degradation) over the same period, respectively. This accelerated degradation is attributed to the increased hydrophilicity from the AA, which allows for faster water penetration into the polymer matrix, thereby facilitating the cleavage of ester bonds.Example 5: Mechanical Properties of 4D Printed Polymers

[0065] Tensile Properties: Reference is made to Table 2 displaying a summary of the tensile properties of the printed polymers.Table 2: Tensile properties of different 4D-printed polymers.

[0066] As seen in the table, the mechanical properties are found to be highly tuneable by varying the AA content. As shown in FIG. 11 A, tensile strength and strain at break increased significantly with AA content. P(AOPO) had a tensile strength of 143 kPa, while P(AOPO)-25AA reached 984 kPa, a nearly 7-fold increase (FIG. 11 B). Similarly, toughness increased over 20- fold from P(AOPO) to P(AOPO)-25AA (FIG. 11 D).

[0067] This enhancement is attributed to the complex network structure containing chemically crosslinked poly(AOPO) segments, flexible poly(AA) chain segments, and their increased physical crosslinking via hydrogen bonding, as illustrated in the schematic in FIG. 4E. This hypothesis is supported by the gel content data, where higher AA content leads to lower chemical crosslinking. When strain is applied, the hydrogen bonds act as sacrificial motifs, breaking to dissipate energy, while the flexible chains stretch to distribute stress, increasing overall toughness and strength.

[0068] Compressive Properties: A similar trend was observed under compression as seen in FIGs. 5A-5O. Reference is now made to these figures. FIG. 5A shows a typical stress-strain curve of P(AOPO), P(AOPO)-10AA and P(AOPO)-25AA; and FIG. 5B - compressive stress and strain of P(AOPO), P(AOPO)-1 OAA and P(AOPO)-25AA. FIG. 5C shows a compressive modulus and toughness of P(AOPO), P(AOPO)-1 OAA and P(AOPO)-25AA. Further, FIGs. 5D-5F show a cyclic compressive loading and unloading experiments at different strain percentage forP(AOPO), P(AOPO)-1 OAA and P(AOPO)-25AA, respectively. FIGs. 5G-5I present the dissipated energy under the hysteresis loop and total energy dissipation during cyclic loading and unloading experiments at different strain percentage for P(AOPO), P(AOPO)-10AAand P(AOPO)- 25AA, respectively. FIGs. 5J-5Lshow ten successive fatigue cycles of printed polymers at 20% strain of P(AOPO), P(AOPO)-1 OAA and P(AOPO)-25AA, respectively. Finally, FIGs. 5M-5O show relative energy dissipation and strength of ten fatigue cycles for P(AOPO), P(AOPO)-1 OAA and P(AOPO)-25AA. Statistical analysis is conducted with two-way ANOVA; *, **, and *** were considered for p values < 0.05, < 0.01 , and < 0.001 respectively (n=3).

[0069] The compressive strength increased from -1374 kPa for P(AOPO) to -8697 kPa for P(AOPO)-25AA, as seen in Table 3 summarisingthe compressive properties.Table 3: Compressive properties of 4D-printed polymers.

[0070] These results align consistently with the data obtained from the tensile experiments. The tuneable mechanical properties of these polymers fall within the range of various human soft tissues, such as aorta, ligaments, and articular cartilage, indicating their suitability for tissue engineering applications.

[0071] Fatigue and Recovery: Cyclic compressive loading-unloading tests showed that P(AOPO)-25AA dissipated a large amount of energy (-42-48%) through the rupture of sacrificial hydrogen bonds, a key feature for toughness, as seen in FIGs. 5F-5L The printed polymers also exhibited excellent self-recovery. After 2 minutes of rest following 20% compressive strain, the polymers recovered with almost no residual strain, demonstrating their suitability for loadbearing applications (FIGs. 12A-12C). All polymers recovered more than 90% of their original stress after ten successive fatigue cycles, indicating robust anti-fatigue characteristics, as seen in FIGs. 5J-5O.

[0072] Notably, the P(AOPO)-25AA formulation exhibited great durability, remainingfracture- free even under large compressive loads. Moreover, the tuneable mechanical properties of the 4D printed polymers align closely with a range of soft tissues in the human body, making them suitable for various implant applications. For instance, the compressive modulus of the printedpolymers (1 .7-3.0 MPa, from Table 3) corresponds well with the elastic modulus of tissues such as elastin from bovine ligament (1.1 MPa), ligamentum flavum (1.5 MPa), and interspinous ligaments (1 .5 MPa). Furthermore, the values are comparable to those of aorta (2.0 to 6.5 MPa) and articular cartilage (2.1 to 1 1 .8 MPa). Collectively, these results clearly demonstrate that by fine-tuning the resin composition, the mechanical properties of the printed objects can be tailored to meet the specific requirements of different soft tissue engineering and implant applications.Example 6: Shape Memory Performance

[0073] All printed polymers exhibited one-way, temperature-responsive shape memory properties. The shape memory cycle was evaluated by deforming a polymer strip into a temporary ‘ U’ shape, fixing it at -20 °C, and then triggering recovery in a 37 °C water bath (FIG. 6A). As shown in FIG. 6B, P(AOPO)-25AA displayed the highest fixity ratio of -99%, while P(AOPO) had the lowest at -70%. The recovery time varied from 40s for P(AOPO) to 100s for P(AOPO)-25AA (FIG. 6C), with the recovery being driven by the release of stored entropic energy as the polymer is heated above its Tg2. Statistical analysis in FIGs. 6B and 6C was conducted with two-way ANOVA; *, **, and *** were considered for p values < 0.05, < 0.01 , and < 0.001 , respectively (n=3).

[0074] FIGs. 6D and 6E show digital photographs of a P(AOPO)-25AA strip recovering from both a ‘ U’ shape and a twisted ‘helix’ shape over time at 37 °C. FIG. 6F demonstrates the potential for medical applications by showing a compressed 4D printed stent of the invention recovering its expanded, functional shape, after fixing it at subzero temperature (-20°C) and then placing at room temperature (25°C).Example 7: Biocompatibility Assessment

[0075] The cytotoxicity and cytocompatibility of the polymer degradation products was assessed using NIH / 3T3 mouse fibroblasts. An Alamar blue assay (FIG. 7A) showed that cells exposed to conditioned media from all polymer types maintained high viability, with over 80% viability after 3 days, indicating excellent cytocompatibility. This was confirmed by live / dead staining (FIGs. 7C-7F), where very few dead (red) cells were observed. Furthermore, cell morphology imaging (FIGs. 7E-7F) showed healthy, well-spread cells sim ilar to the control group, reinforcing the non-toxic nature of the materials. A blood compatibility(hemocompatibility) study (FIG. 7B) revealed an exceptionally low haemolysis index of less than 1 % for all printed polymers, confirming they are safe for applications involving direct contact with blood. Statistical analysis in FIGs. 7A-7Bwas conducted with two-way ANOVA; *, **, and *** were considered for p values < 0.05, < 0.01 , and < 0.001 , respectively (n=3).Example 8: Antibacterial Activity

[0076] The inherent antibacterial properties of the 4D printed polymers were tested against gram-negative E coZ / and gram-positive B. subtilis using a direct contact model. As shown in the growth kinetics and corresponding agar plates in FIG. 8A (for E coli) and in FIG. 8B (for B. subtilis), all polymer compositions completely inhibited the growth of both bacterial strains. Live / dead fluorescence imaging (FIGs. 8C and 8D, respectively) further confirmed these results, showing viable, untreated bacteria (green) versus dead bacteria (red / yellow) on polymer surfaces. SEM imaging (FIGs. 8Eand 8F, respectively) revealed that bacteria in contact with the polymers had damaged and ruptured membranes, while control bacteria remained intact, confirming a bactericidal mechanism.Example 9: Drug Release Study

[0077] To demonstrate the potential of the material as a drug delivery vehicle, progesterone was incorporated into the AOPO-25AA resin formulation. Progesterone crystals (FIG. 13A) were prepared via asolvent-antisolvent method. Apredetermined amount (3.67 mg) of these crystals was then thoroughly mixed with 788.34 mg of the AOPO-25AA resin. The mixture was photopolymerised into discs, designated P(AOPO-25AA)-Pro. The unreacted resin was washed with hexane. FIG. 13B shows a microscope image of the crystals embedded within the translucent polymer matrix.

[0078] The in vitro release of progesterone from P(AOPO-25AA)-Pro was conducted in phosphate-buffered saline (PBS) with 0.2% sodium dodecyl sulphate (SDS) at 37°C and monitored by HPLC. The polymer discs exhibited a sustained release profile of progesterone over 24 hours. Before the release study, a calibration curve for progesterone was established using HPLC. The release study was performed in triplicate. The cumulative profile shows a steady, controlled release, reaching approximately 0.25% of the total loaded drug after 24 hours. This demonstrates the capability of the 4D printed polymer to act as a long-term drug delivery device.

Claims

CLAIMS1. A photopolymerisable composition comprising: an acrylated polyol (AOPO) derived from a natural oil; and acrylic acid (AA) as a diluent and comonomer.

2. The photopolymerisable composition of claim 1 , further comprising at least one active agent.

3. The photopolymerisable composition of claim 2, wherein the active agent is a therapeutic agent.

4. The photopolymerisable composition of claim 3, wherein the therapeutic agent is progesterone.

5. The photopolymerisable composition of any one of claims 2 to 4, wherein the active agent is in a crystalline form .

6. The photopolymerisable composition of any one of the preceding claims, wherein said natural oil is selected from the group consisting of olive oil, soybean oil, canola oil, sunflower oil, sesame oil, linseed oil, safflower oil, peanut oil, corn oil, walnut oil, and grapeseed oil.

7. The photopolymerisable composition of any one of the preceding claims, further comprising a photoinitiator.

8. The photopolymerisable composition of claim 7, comprising: (a) 75-100 wt% of the acrylated polyol (AOPO) derived from olive oil ; (b) 0-25 wt% of the acrylic acid (AA); and (c) 0.5-3 wt% of a photoinitiator, wherein the weight percentages of the photoinitiator are based on the total weight of AOPO and AA.

9. The photopolymerisable composition of claim 8, wherein the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide.

10. The photopolymerisable composition of any one of the preceding claims, wherein the acrylated polyol is synthesised from said natural oil via a two-stage process comprising: (i) a first stage of epoxidation of said natural oil to form an epoxidised natural oil ; and (ii) a second stage of ring-opening of the epoxidised natural oil with 2- hydroxyethyl acrylate.11 . A4D printed object formed from the photopolymerisable composition of any one of claims 1 to 10.

12. The 4D printed object of claim 11 , wherein the object exhibits temperature-responsive shape memory properties.

13. The 4D printed object of claim 12, wherein the shape memory properties are activated with a transition temperature near human body temperature.

14. The 4D printed object of any one of claims 11 to 13, wherein the object exhibits antimicrobial properties against gram-negative and gram-positive bacteria.

15. The 4D printed object of any one of claims 11 to 14, wherein the object is biocompatible, hemocompatible, and / or cytocompatible.

16. The 4D printed object of any one of claims 11 to 15, wherein the object has mechanical properties similar to at least one soft tissue selected from the group consisting of ligaments, aorta, articular cartilage, and soft collagenous bone.

17. The 4D printed object of claim 11 , wherein the object is formed from the com position of any one of claims 2 to 5 and is configured for the controlled release of the at least one active agent.

18. A method of 4D printing an object, comprising: (i) providing the photopolymerisable composition of any one of claims 1 to 10; (ii) depositing the composition layer-by-layer according to a digital design using a digital light processing (DLP) 3D printer; and (iii) photopolymerising each deposited layer to form the object.

19. The method of claim 18, wherein each deposited layer is photopolymerised to achieve a z- resol ution of 50 pm or less, preferably about 20 pm .

20. The method of claim 18 or 19, wherein the photopolymerisable composition is that of any one of claims 2 to 5, and the step of providing the composition comprises mixing the at least one active agent into the composition prior to depositing.21 . A4D printed object according to any one of claims 11 to 17 for use in a medical appl ication .

22. The 4D printed object for use according to claim 21 , wherein the medical application is selected from the group consisting of a medical implant, a dental filling, a drug delivery device, an orthopaedic screw, a cardiovascular stent, a catheter, and a nerve conduit.

23. The 4D printed object for use according to claim 22, wherein the object is a biodegradable long-term drug deliverydevice.

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