Non-spherical porous foam material as well as preparation method and application thereof

Abstract

The invention provides a non-spherical porous foam material and a preparation method and application thereof, the preparation method comprises the following steps: (1) mixing a polymerizable monomer, a cross-linking agent, an emulsifier, a stabilizer and an initiator to obtain an oil phase; (2) mixing deionized water, electrolyte and an initiator to obtain a water phase; (3) preparing a rodlike high internal phase emulsion or an ellipsoidal high internal phase emulsion from the oil phase and the water phase by adopting microfluidic equipment; and (4) carrying out ultraviolet precuring on the rodlike high-internal-phase emulsion or the ellipsoidal high-internal-phase emulsion, and then carrying out thermocuring and post-treatment to respectively obtain a rodlike porous foam material or an ellipsoidal porous foam material, namely the non-spherical porous foam material. The invention provides an accurate preparation scheme of the non-spherical HIPE based on a microfluidic technology, controllable preparation of the non-spherical HIPE is realized, and the non-spherical porous foam material formed after curing can provide a high-performance carrier for 3D cell culture in the fields of regeneration, repair and the like.

Description

Technical Field

[0001] This invention belongs to the field of porous foam material technology, and relates to a non-spherical porous foam material, its preparation method and application. Background Technology

[0002] High internal phase emulsion (HIPE, internal phase volume fraction ≥74%) forms porous materials after solidification. Due to its high porosity, large specific surface area, and tunable biocompatibility, it has become one of the core carriers for 3D cell culture and can also be used in daily hygiene products (such as sanitary napkins and dressings). However, existing technologies face bottlenecks that are difficult to overcome.

[0003] 1. Limited morphology: Traditional HIPE relies on the "shear emulsification-random stacking" process, which can only prepare spherical droplets. After solidification, it forms a disordered porous structure, which cannot simulate the in vivo microenvironment and cannot meet the "structure-function matching" requirements of tissue engineering.

[0004] 2. Difficulty in preparing non-spherical HIPE: Existing methods for preparing non-spherical emulsions (such as mechanical extrusion and template constraint) are difficult to adapt to the high viscosity characteristics of HIPE: mechanical extrusion easily leads to the coalescence of the HIPE aqueous phase; template constraint cannot achieve continuous preparation.

[0005] 3. Morphological stability: Even if non-spherical HIPE is obtained through external force, it is easy to rebound into a spherical shape before curing due to the high interfacial tension of HIPE; and traditional curing process (oven heating) is prone to pore collapse due to thermal stress, further reducing the utilization rate of 3D cell growth space.

[0006] Therefore, developing a preparation method that can achieve "precise preparation of non-spherical HIPE" has become the key to breaking through the performance bottleneck of 3D cell culture carriers. Summary of the Invention

[0007] To address the shortcomings of existing technologies, the present invention aims to provide a non-spherical porous foam material, its preparation method, and its applications. Specifically, the present invention addresses the core pain points of traditional high internal phase emulsions (HIPEs), namely, the inability to prepare spherical shapes with limited morphology, the resulting uneven microenvironment for 3D cell growth due to disordered pores, and the difficulty in directional control and poor stability of non-spherical morphology. It provides a precise preparation scheme for non-spherical HIPEs based on microfluidic technology, enabling the controllable preparation of rod-shaped, ellipsoidal, and other non-spherical HIPEs. Furthermore, the anisotropic porous structure formed after solidification can meet the requirements of "directional growth and differentiation induction" in 3D cell culture, ultimately improving cell colonization rate and directional differentiation efficiency, and providing a high-performance carrier for 3D cell culture in regeneration, repair, and other fields.

[0008] To achieve this objective, the present invention employs the following technical solution:

[0009] In a first aspect, the present invention provides a method for preparing a non-spherical porous foam material, the method comprising the following steps:

[0010] (1) Mix polymerizable monomers, crosslinking agents, emulsifiers, stabilizers and initiators to obtain a uniform and transparent oil phase;

[0011] (2) Mix deionized water, electrolyte, and initiator to obtain an aqueous phase;

[0012] (3) Using a microfluidic device, the oil phase is injected into the oil phase channel of the T-shaped sheath microchannel, and the aqueous phase is injected into the inner phase channel. The flow rates of the oil phase and the aqueous phase are set to mix the oil and aqueous phases, initially forming spherical droplets. The spherical droplets are then introduced into the contraction and expansion channels, and the centrifugation module is activated simultaneously to stretch the spherical droplets into rod-shaped droplets, thus obtaining a rod-shaped high-internal-phase emulsion; or,

[0013] Using a microfluidic device, the oil phase is injected into the outer sheath flow channel of a four-channel eccentric coaxial microchannel, and the aqueous phase is injected into the inner eccentric channel. The flow velocities on the left and right sides of the outer sheath flow channel and the flow velocity of the inner eccentric channel are set. The mixed droplets are squeezed into ellipsoidal droplets by asymmetric shear force to obtain an ellipsoidal high internal phase emulsion.

[0014] (4) Within 0.5 seconds after the preparation of the rod-shaped high internal phase emulsion or the ellipsoidal high internal phase emulsion, it is subjected to UV pre-curing, then heat curing, and post-treatment to obtain rod-shaped porous foam material or ellipsoidal porous foam material respectively, that is, the non-spherical porous foam material is obtained.

[0015] The core of the technical solution of this invention lies in constructing a three-in-one technical system of "microfluidic composite force field deformation - interface stabilization enhancement - stepwise in-situ solidification" to achieve controllable preparation of non-spherical HIPE and adaptation to 3D cell culture, specifically including:

[0016] 1) Utilizing composite force fields to drive non-spherical deformation: To meet the morphological requirements of rod-shaped and ellipsoidal HIPEs, differentiated microfluidic channels and force field combinations are designed. Rod-shaped HIPEs employ a force field of "T-shaped sheath flow pre-emulsification + contraction-expansion channel stretching + centrifugal force assistance" to achieve directional deformation through the stretching effect. Ellipsoidal HIPEs employ a force field of "eccentric coaxial sheath flow + dynamic velocity difference" to achieve adjustable deformation through asymmetric shear force, avoiding morphological inhomogeneity caused by a single force field.

[0017] 2) Interface stabilization enhancement technology: The "emulsifier + stabilizer" compound system can be adsorbed on the HIPE oil-water interface to form a rigid film, improve the interfacial elastic modulus, and suppress the rebound tendency of non-spherical HIPE.

[0018] 3) Step-by-step in-situ curing and locking technology: Construct a two-step method of "UV pre-curing + high temperature deep curing" - UV pre-curing is initiated within 0.5 seconds after non-spherical deformation to quickly lock the shape; the skeleton is then strengthened by high temperature deep curing.

[0019] Preferably, the polymerizable monomer includes any one or a combination of at least two of acrylate monomers, vinyl monomers, and biodegradable monomers.

[0020] Preferably, the acrylate monomers include monofunctional alkyl acrylates or alkyl methacrylates.

[0021] Preferably, the acrylate monomers include any one or a combination of at least two of C4-C18 alkyl acrylates or C2-C18 methacrylates.

[0022] Preferably, the acrylate monomers include any one or a combination of at least two of the following: 2-ethylhexyl acrylate (EHA), n-butyl acrylate, hexyl acrylate, n-octyl acrylate, n-nonyl acrylate, n-decyl acrylate, isodecyl acrylate, n-tetradecyl acrylate, benzyl acrylate, nonylphenyl acrylate, n-hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, isooctyl methacrylate, n-decyl methacrylate, isodecyl methacrylate, n-dodecyl methacrylate, n-tetradecyl methacrylate, and n-octadecyl methacrylate.

[0023] Preferably, the vinyl monomers include styrene (STY) monomers and / or vinyltoluene.

[0024] Preferably, the biodegradable monomer comprises PLA prepolymer.

[0025] Preferably, the crosslinking agent comprises a multifunctional crosslinking monomer.

[0026] Preferably, the crosslinking agent comprises any one or a combination of at least two of ethylene glycol dimethacrylate (EGDMA), trihydroxypropane trimethacrylate (TMPTA), divinylbenzene (DVB), and 1,6-hexanediol diacrylate (HDDA).

[0027] Preferably, the emulsifier comprises any one or a combination of at least two of Span 80, Span 60, polyglycerol ricinoleate, polyglycerol stearate, and polyglycerol oleate.

[0028] Preferably, the stabilizer comprises any one or a combination of at least two of the following: nano-silica, nano-zirconium phosphate, nano-zinc oxide, nano-titanium dioxide, graphene oxide, polystyrene nanospheres, or polylactic acid-glycolic acid copolymer nanoparticles.

[0029] Preferably, the initiator in the oil phase is a photoinitiator, including any one or a combination of at least two of the following: photoinitiator TPOL, photoinitiator TPO, photoinitiator 184, and photoinitiator 1173.

[0030] Preferably, the oil phase comprises, by weight, the following components: 40-80 parts of polymerizable monomers (e.g., 40, 42, 44, 45, 46, 48, 50, 52, 54, 55, 56, 58, 60, 62, 64, 65, 66, 68, 70, 72, 74, 75, 76, 78, 80, etc.); and 2-30 parts of crosslinking agent (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 15, 16, 18, 20 parts). 22 parts, 24 parts, 25 parts, 26 parts, 28 parts, 30 parts, etc.), emulsifier 1-20 parts (e.g., 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 12 parts, 14 parts, 15 parts, 16 parts, 18 parts, 20 parts, etc.), stabilizer 0.5-5 parts (e.g., 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, etc.), initiator 0.5-5 parts (e.g., 0.5 parts, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, etc.).

[0031] Preferably, the mixing method in step (1) includes magnetic stirring.

[0032] Preferably, the mixing temperature in step (1) is 25-35℃, such as 25℃, 30℃, 35℃, etc., and the mixing time is 20-40min, such as 20min, 25min, 30min, 35min, 40min, etc.

[0033] Preferably, the electrolyte comprises calcium chloride and / or sodium chloride.

[0034] Preferably, the initiator in the aqueous phase comprises persulfate.

[0035] Preferably, the persulfate includes any one or a combination of at least two of potassium persulfate, sodium persulfate, and ammonium persulfate.

[0036] Preferably, based on the total mass of the aqueous phase as 100%, the content of the electrolyte is 0.5%-5%, such as 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, etc., and the content of the initiator is 0.1%-1%, such as 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, etc.

[0037] Preferably, the inner diameter of the oil phase channel in step (3) is 150-250μm, such as 150μm, 160μm, 170μm, 180μm, 190μm, 200μm, 210μm, 220μm, 230μm, 240μm, 250μm, etc.

[0038] Preferably, the inner diameter of the inner phase channel in step (3) is 80-120 μm, such as 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, etc.

[0039] Preferably, the oil phase flow rate in step (3) is 50-70 μL / min, such as 50 μL / min, 55 μL / min, 60 μL / min, 65 μL / min, 70 μL / min, etc.

[0040] Preferably, the aqueous phase flow rate in step (3) is 120-300 μL / min, such as 120 μL / min, 140 μL / min, 160 μL / min, 180 μL / min, 200 μL / min, 220 μL / min, 240 μL / min, 250 μL / min, 260 μL / min, 280 μL / min, 300 μL / min, etc.

[0041] Preferably, the ratio of the oil phase flow rate to the water phase flow rate in step (3) is 1:(2-5), such as 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, etc.

[0042] Preferably, the diameter of the spherical droplet in step (3) is 120-150 μm, such as 120 μm, 125 μm, 130 μm, 135 μm, 140 μm, 145 μm, 150 μm, etc.

[0043] Preferably, the inner diameter of the contraction section of the contraction-expansion channel in step (3) is 40-60μm, such as 40μm, 45μm, 50μm, 55μm, 60μm, etc., and the inner diameter of the expansion section is 70-90μm, such as 70μm, 75μm, 80μm, 85μm, 90μm, etc., and the length is 1-3mm, such as 1mm, 1.5mm, 2mm, 2.5mm, 3mm, etc.

[0044] Preferably, the acceleration of the centrifuge module in step (3) is 200-400g, such as 200g, 250g, 300g, 350g, 400g, etc.

[0045] Preferably, the aspect ratio of the rod-shaped droplet in step (3) is (3-5):1, such as 3:1, 3.5:1, 4:1, 4.5:1, 5:1, etc.

[0046] Preferably, the inner diameter of the outer sheath flow channel in step (3) is 200-400μm, such as 200μm, 250μm, 300μm, 350μm, 400μm, etc.

[0047] Preferably, the inner diameter of the inner eccentric channel in step (3) is 80-120μm, such as 80μm, 85μm, 90μm, 95μm, 100μm, 105μm, 110μm, 115μm, 120μm, etc., and the eccentricity is 50-70μm, such as 50μm, 55μm, 60μm, 65μm, 70μm, etc.

[0048] Preferably, in step (3), the flow velocity on the left side of the outer sheath flow channel is 140-160 μL / min (e.g., 140 μL / min, 145 μL / min, 150 μL / min, 155 μL / min, 160 μL / min, etc.), and the flow velocity on the right side is 70-90 μL / min (e.g., 70 μL / min, 75 μL / min, 80 μL / min, 85 μL / min, 90 μL / min, etc.).

[0049] Preferably, the flow rate of the inner eccentric channel in step (3) is 40-60 μL / min, such as 40 μL / min, 45 μL / min, 50 μL / min, 55 μL / min, 60 μL / min, etc.

[0050] Preferably, the aspect ratio of the ellipsoidal droplet in step (3) is (1.5-2.5):1, such as 1.5:1, 1.6:1, 1.8:1, 2:1, 2.2:1, 2.3:1, 2.5:1, etc.

[0051] Preferably, the wavelength of the ultraviolet light used in step (4) for ultraviolet pre-curing is 300-400nm, such as 300nm, 320nm, 340nm, 350nm, 360nm, 380nm, 400nm, etc.

[0052] Preferably, the power of the UV pre-curing in step (4) is 80-100W, such as 80W, 85W, 90W, 95W, 100W, etc., and the UV pre-curing time is 15-40 seconds, such as 15 seconds, 20 seconds, 25 seconds, 30 seconds, 35 seconds, 40 seconds, etc. The degree of curing after UV pre-curing is 30%-40%, such as 30%, 32%, 34%, 35%, 36%, 38%, 40%, etc.

[0053] Preferably, the thermosetting in step (4) is carried out in an oven.

[0054] Preferably, the temperature for heat curing in step (4) is 70-90℃, such as 70℃, 75℃, 80℃, 85℃, 90℃, etc., and the heat curing time is 1-3h, such as 1h, 2h, 3h, etc.

[0055] Preferably, the post-processing in step (4) includes washing and drying.

[0056] As a preferred embodiment of the present invention, the preparation method includes the following steps:

[0057] (1) Mix 40-80 parts of polymerizable monomer, 2-30 parts of crosslinking agent, 1-20 parts of emulsifier, 0.5-5 parts of stabilizer and 0.5-5 parts of initiator at 25-35℃ for 20-40 min to obtain oil phase;

[0058] (2) Mix deionized water, electrolyte, and initiator to obtain an aqueous phase;

[0059] Wherein, based on the total mass of the aqueous phase as 100%, the content of the electrolyte is 0.5%-5%, and the content of the initiator is 0.1%-1%.

[0060] (3) Using a microfluidic device, the oil phase is injected into the oil phase channel of the T-shaped sheath flow microchannel. The inner diameter of the oil phase channel is 150-250 μm. The aqueous phase is injected into the inner phase channel. The inner diameter of the inner phase channel is 80-120 μm. The flow rate of the oil phase is set to 50-70 μL / min and the flow rate of the aqueous phase is set to 120-300 μL / min. The oil and aqueous phases are mixed to initially form spherical droplets with a diameter of 120-150 μm. The spherical droplets are then introduced into the contraction-expansion channel. The inner diameter of the contraction section of the contraction-expansion channel is 40-60 μm, the inner diameter of the expansion section is 70-90 μm, and the length is 1-3 mm. At the same time, the centrifugation module is started with an acceleration of 200-400 g to stretch the spherical droplets into rod-shaped droplets with an aspect ratio of (3-5):1, thus obtaining a rod-shaped high inner phase emulsion; or,

[0061] Using a microfluidic device, the oil phase is injected into the outer sheath flow channel of a four-channel eccentric coaxial microchannel. The inner diameter of the outer sheath flow channel is 200-400 μm. The aqueous phase is injected into the inner eccentric channel. The inner diameter of the inner eccentric channel is 80-120 μm and the eccentricity is 50-70 μm. The flow velocity on the left side of the outer sheath flow channel is set to 140-160 μL / min, the flow velocity on the right side is set to 70-90 μL / min, and the flow velocity in the inner eccentric channel is set to 40-60 μL / min. The mixed droplets are squeezed into ellipsoidal droplets with an aspect ratio of (1.5-2.5):1 by asymmetric shear force, resulting in an ellipsoidal high internal phase emulsion.

[0062] (4) After the preparation of the rod-shaped high internal phase emulsion or the ellipsoidal high internal phase emulsion, it is subjected to ultraviolet pre-curing within 0.5 seconds. The wavelength of the ultraviolet light used for ultraviolet pre-curing is 300-400nm, the power of ultraviolet pre-curing is 80-100W, and the time is 15-40 seconds. Then, it is heat-cured in an oven at 70-90℃ for 1-3 hours, washed, and dried to obtain rod-shaped porous foam material or ellipsoidal porous foam material, which is the non-spherical porous foam material.

[0063] In a second aspect, the present invention provides a non-spherical porous foam material, which is prepared by the preparation method described in the first aspect.

[0064] Preferably, the non-spherical porous foam material is a rod-shaped porous foam material or an ellipsoidal porous foam material.

[0065] Preferably, the pore diameter in the rod-shaped porous foam material is 70-90 μm (e.g., 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, etc.), and the pore length is 300-350 μm (e.g., 300 μm, 310 μm, 320 μm, 330 μm, 340 μm, 350 μm, etc.).

[0066] Preferably, the pore connectivity rate in the rod-shaped porous foam material is greater than 90%, such as 92%, 94%, 95%, 96%, 98%, etc.

[0067] Preferably, the compression modulus of the rod-shaped porous foam material is 0.5-2 MPa, such as 0.5 MPa, 1 MPa, 1.5 MPa, 2 MPa, etc.

[0068] Preferably, the pore diameter of the ellipsoidal porous foam material is 50-80 μm (e.g., 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, etc.), and the pore length is 90-200 μm (e.g., 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm, etc.).

[0069] Preferably, the pore connectivity rate in the ellipsoidal porous foam material is greater than 90%, such as 92%, 94%, 95%, 96%, 98%, etc.

[0070] Preferably, the compressive modulus of the ellipsoidal porous foam material is 0.4-1.8 MPa, such as 0.4 MPa, 0.5 MPa, 0.6 MPa, 0.8 MPa, 1 MPa, 1.2 MPa, 1.3 MPa, 1.5 MPa, 1.8 MPa, etc.

[0071] Thirdly, the present invention provides an application of the non-spherical porous foam material as described in the second aspect in 3D cell culture, pharmaceutical dressings, and daily chemical hygiene products.

[0072] Preferably, the 3D cell culture includes 3D culture of vascular endothelial cells.

[0073] In particular, the non-spherical porous foam material can also be used in the field of daily chemical hygiene products such as sanitary napkins and dressings. The prepared non-spherical porous foam material can further improve the absorption, flow, and water-locking effects of the material, and enhance the dryness and long-lasting performance of the product.

[0074] Compared with the prior art, the present invention has the following beneficial effects:

[0075] (1) This invention achieves the controllable preparation of non-spherical HIPE and non-spherical porous foam materials by constructing a three-in-one technical system of "microfluidic composite force field deformation - interface stabilization enhancement - stepwise in-situ curing", as follows:

[0076] ① Innovative Deformation of Composite Force Field: By using the combination of microfluidic force fields of "T-shaped sheath flow stretching + centrifugal assistance" (to obtain rod-shaped HIPE) or "eccentric coaxial sheath flow + dynamic velocity difference" (to obtain ellipsoidal HIPE), the problem of non-spherical directional deformation of high-viscosity HIPE is overcome, and the uniformity of droplet shape far exceeds that of traditional mechanical extrusion method.

[0077] ② Interface stabilization technology innovation: The use of a compound system of "emulsifier + stabilizer" improves the elastic modulus of the HIPE interface, extending the stabilization time of non-spherical morphology to more than 30 minutes;

[0078] ③ Step-by-step curing locks in innovation: Utilizing a two-step method of "UV pre-curing + deep curing by heating" to avoid the rebound of non-spherical shapes.

[0079] (2) 3D cell adaptation design: The non-spherical porous foam material provided by the present invention can accurately match the non-spherical morphological parameters (length-to-diameter ratio, pore size) with the cell requirements, improve the directed growth rate of cells in the pores (≥85%), and achieve “structure-function” synergy. Attached Figure Description

[0080] Figure 1 The image shows an SEM image of the ellipsoidal porous foam material provided in Example 5. Detailed Implementation

[0081] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0082] Unless otherwise specified, the raw material information used in the following embodiments and comparative examples of the present invention is as follows:

[0083] PLA prepolymer, NatureWorks, model 4032;

[0084] 2-Ethylhexyl acrylate, Maclean, E808951;

[0085] EGDMA, McLean, E808858;

[0086] TMPTA, McLean, T818690;

[0087] Styrene, Maclean's, S817904;

[0088] Divinylbenzene, Maclean, D806657;

[0089] SPAN 60, Wharf Holdings, UK;

[0090] SPAN 80, Croda, UK;

[0091] Polyglycerol ricinoleate, Croda, UK;

[0092] Polyglycerol stearate, Jinsheng New Materials, Binzhou, Shandong;

[0093] TPO, Guangdong Lankelu New Materials;

[0094] Photoinitiator 184, Guangdong Lankelu New Materials;

[0095] Photoinitiator 1173, Guangdong Lankelu New Materials;

[0096] Calcium chloride, Sinopharm Group;

[0097] Sodium chloride, Chinese medicine group;

[0098] Sodium persulfate, Fujian Zhanhua Chemical Co., Ltd.

[0099] Potassium persulfate, Fujian Zhanhua Chemical Co., Ltd.

[0100] Ammonium persulfate, produced by Fujian Zhanhua Chemical Co., Ltd.

[0101] Example 1

[0102] This embodiment provides a non-spherical porous foam material (specifically a rod-shaped porous foam material), and the preparation method includes the following steps:

[0103] (1) Mix 40 parts of polymerizable monomer (PLA prepolymer), 10 parts of crosslinking agent (EGDMA), 3 parts of emulsifier (SPAN80), 1 part of stabilizer (nano silica), and 1 part of initiator (photoinitiator TPOL) at 30°C for 30 min to obtain the oil phase;

[0104] (2) Deionized water, electrolyte (calcium chloride), and initiator (ammonium persulfate) are mixed to obtain an aqueous phase;

[0105] Wherein, based on the total mass of the aqueous phase as 100%, the content of the electrolyte is 2%, and the content of the initiator is 0.5%;

[0106] (3) Using a microfluidic device, the oil phase is injected into the oil phase channel of the T-shaped sheath flow microchannel. The inner diameter of the oil phase channel is 200 μm. The water phase is injected into the inner phase channel. The inner diameter of the inner phase channel is 100 μm. The oil phase flow rate is set to 60 μL / min and the water phase flow rate is set to 180 μL / min. The oil phase and water phase are mixed to initially form spherical droplets with a diameter of 130 μm. The spherical droplets are then introduced into the contraction and expansion channel. The contraction section of the contraction and expansion channel has an inner diameter of 50 μm, the expansion section has an inner diameter of 80 μm, and the length is 2 mm. At the same time, the centrifugation module is started with an acceleration of 300 g to stretch the spherical droplets into rod-shaped droplets with a length-to-diameter ratio of 4:1, thus obtaining a rod-shaped high inner phase emulsion.

[0107] (4) Within 0.5 seconds after the preparation of the rod-shaped high internal phase emulsion, it is subjected to ultraviolet pre-curing, wherein the wavelength of the ultraviolet light used for ultraviolet pre-curing is 365nm, the power of ultraviolet pre-curing is 90W, and the time is 30 seconds. Then, it is heat-cured in an oven at 80℃ for 2 hours, washed, and dried to obtain rod-shaped porous foam material, that is, the non-spherical porous foam material.

[0108] Examples 2-4

[0109] The only difference from Example 1 is that the types and / or amounts of raw materials, preparation conditions, etc. are different, as shown in Table 1. All items not shown in Table 1 are considered to be the same as those in Example 1.

[0110] Table 1

[0111]

[0112] Example 5

[0113] This embodiment provides a non-spherical porous foam material (specifically an ellipsoidal porous foam material), the preparation method of which includes the following steps:

[0114] (1) Mix 50 parts of polymerizable monomer (2-ethylhexyl acrylate), 8 parts of crosslinking agent (TMPTA), 5 parts of emulsifier (polyglycerol ricinoleate), 2 parts of stabilizer (nano silica, D50 particle size of 20nm), and 1.5 parts of initiator (photoinitiator 184) at 30℃ for 30min to obtain an oil phase;

[0115] (2) Deionized water, electrolyte (sodium chloride), and initiator (sodium persulfate) are mixed to obtain an aqueous phase;

[0116] Wherein, based on the total mass of the aqueous phase as 100%, the content of the electrolyte is 1%, and the content of the initiator is 0.3%;

[0117] (3) Using a microfluidic device, the oil phase is injected into the outer sheath flow channel of the four-channel eccentric coaxial microchannel. The inner diameter of the outer sheath flow channel is 300 μm. The water phase is injected into the inner eccentric channel. The inner diameter of the inner eccentric channel is 100 μm and the eccentricity is 60 μm. The flow velocity on the left side of the outer sheath flow channel is set to 150 μL / min and the flow velocity on the right side is set to 80 μL / min. The flow velocity of the inner eccentric channel is set to 50 μL / min. The mixed droplets are squeezed into ellipsoidal droplets with an aspect ratio of 2:1 by asymmetric shear force to obtain ellipsoidal high internal phase emulsion.

[0118] (4) After the ellipsoidal high internal phase emulsion is prepared, it is subjected to ultraviolet pre-curing within 0.5 seconds. The wavelength of the ultraviolet light used for ultraviolet pre-curing is 365nm, the power of ultraviolet pre-curing is 90W, and the time is 30 seconds. Then, it is heat-cured in an oven at 80℃ for 2 hours, washed, and dried to obtain the ellipsoidal porous foam material, that is, the non-spherical porous foam material.

[0119] The SEM image of the ellipsoidal porous foam material provided in this embodiment is as follows: Figure 1 As shown.

[0120] Examples 6-8

[0121] The only difference from Example 5 is that the types and / or amounts of raw materials, preparation conditions, etc. are different, as shown in Table 2. All items not shown in Table 2 are considered to be the same as those in Example 5.

[0122] Table 2

[0123]

[0124] Comparative Example 1

[0125] The only difference between this comparative example and Example 1 is that there is no shrinkage expansion channel and centrifugal module in step (3), and spherical droplets are directly prepared; there is no UV pre-curing in step (4), only heat curing; the product obtained is a spherical porous foam material with disordered pores.

[0126] Comparative Example 2

[0127] The only difference between this comparative example and Example 1 is that the oil phase does not contain a stabilizer (nano silica).

[0128] Comparative Example 3

[0129] The only difference between this comparative example and Example 1 is that UV pre-curing is not performed in step (4).

[0130] Comparative Example 4

[0131] The only difference between this comparative example and Example 1 is that thermal curing is not performed in step (4), and the UV pre-curing time is extended to 2 minutes.

[0132] The performance of the high internal phase emulsion and porous foam material provided in the embodiments and comparative examples of the present invention was tested using the following methods:

[0133] (1) Morphological stability: The droplets of the high internal phase emulsion were placed at room temperature for 30 min, the length-to-diameter ratio of the droplets was measured, and the rate of change was calculated.

[0134] (2) Foam and channel morphology: The morphology of non-spherical high internal phase emulsion was observed by optical microscope; the morphology of porous foam material was observed by scanning electron microscope (SEM), and the channel diameter, channel length and channel connectivity were recorded.

[0135] (3) Compression modulus: The porous foam material was tested using a universal testing machine (Instron 5967). The sample size was 10mm×10mm×10mm, the compression rate was 1mm / min, and the stress at 8% strain was taken.

[0136] (4) Cell directional growth rate: After 7 days, the directional growth rate (the percentage of cells growing along the pore direction) is calculated by seeding vascular endothelial cells in porous foam material.

[0137] (5) Porosity: The liquid displacement method (anhydrous ethanol) was used for testing. The porous foam material sample was vacuum dried at 50℃ for 12h, weighed and recorded as m1; the dried sample was immersed in anhydrous ethanol for vacuum degassing for 30min, and weighed after saturation and recorded as m2; the volume V was measured by the water displacement method. .

[0138] The performance test results are shown in Table 3.

[0139] Table 3

[0140]

[0141] As can be seen from Table 3, the non-spherical high internal phase emulsions provided in Examples 1-8 have stable morphology (30 min aspect ratio change rate ≤7%), pore connectivity of non-spherical porous foam materials ≥90%, and cell directional growth rate ≥85%, which are significantly better than the comparative examples, proving the effectiveness of the "composite force field + stabilizer + stepwise curing" technology system of the present invention.

[0142] The applicant declares that this invention illustrates the non-spherical porous foam material, its preparation method, and its application through the above embodiments. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials used in this invention, additions of auxiliary components, and selection of specific methods all fall within the protection and disclosure scope of this invention.

Claims

1. A method for preparing a non-spherical porous foam material, characterized in that, The preparation method includes the following steps: (1) Mix polymerizable monomers, crosslinking agents, emulsifiers, stabilizers and initiators to obtain an oil phase; (2) Mix deionized water, electrolyte, and initiator to obtain an aqueous phase; (3) Using a microfluidic device, the oil phase is injected into the oil phase channel of the T-shaped sheath microchannel, and the aqueous phase is injected into the inner phase channel. The flow rates of the oil phase and the aqueous phase are set to mix the oil and aqueous phases, initially forming spherical droplets. The spherical droplets are then introduced into the contraction and expansion channels, and the centrifugation module is activated simultaneously to stretch the spherical droplets into rod-shaped droplets, thus obtaining a rod-shaped high-internal-phase emulsion; or, Using a microfluidic device, the oil phase is injected into the outer sheath flow channel of a four-channel eccentric coaxial microchannel, and the aqueous phase is injected into the inner eccentric channel. The flow velocities on the left and right sides of the outer sheath flow channel and the flow velocity of the inner eccentric channel are set. The mixed droplets are squeezed into ellipsoidal droplets by asymmetric shear force to obtain an ellipsoidal high internal phase emulsion. (4) Within 0.5 seconds after the preparation of the rod-shaped high internal phase emulsion or the ellipsoidal high internal phase emulsion, it is subjected to UV pre-curing, then heat curing, and post-treatment to obtain rod-shaped porous foam material or ellipsoidal porous foam material respectively, that is, the non-spherical porous foam material is obtained.

2. The preparation method according to claim 1, characterized in that, The polymerizable monomers include any one or a combination of at least two of acrylate monomers, vinyl monomers, and biodegradable monomers; Preferably, the acrylate monomers include monofunctional alkyl acrylates or alkyl methacrylates; Preferably, the acrylate monomers include any one or a combination of at least two of C4-C18 alkyl acrylates or C2-C18 methacrylates; Preferably, the acrylate monomers include any one or a combination of at least two of the following: 2-ethylhexyl acrylate, n-butyl acrylate, hexyl acrylate, n-octyl acrylate, n-nonyl acrylate, n-decyl acrylate, isodecyl acrylate, n-tetradecyl acrylate, benzyl acrylate, nonylphenyl acrylate, n-hexyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, isooctyl methacrylate, n-decyl methacrylate, isodecyl methacrylate, n-dodecyl methacrylate, n-tetradecyl methacrylate, and n-octadecyl methacrylate. Preferably, the vinyl monomers include styrene monomers and / or vinyltoluene; Preferably, the biodegradable monomer comprises PLA prepolymer.

3. The preparation method according to claim 1 or 2, characterized in that, The crosslinking agent includes a multifunctional crosslinking monomer; Preferably, the crosslinking agent comprises any one or a combination of at least two of ethylene glycol dimethacrylate, trihydroxypropane trimethacrylate, divinylbenzene, and 1,6-hexanediol diacrylate; Preferably, the emulsifier comprises any one or a combination of at least two of Span 80, Span 60, polyglycerol ricinoleate, polyglycerol stearate, and polyglycerol oleate; Preferably, the stabilizer comprises any one or a combination of at least two of the following: nano-silica, nano-zirconium phosphate, nano-zinc oxide, nano-titanium dioxide, graphene oxide, polystyrene nanospheres, or polylactic acid-glycolic acid copolymer nanoparticles. Preferably, the initiator in the oil phase is a photoinitiator, including any one or a combination of at least two of the following: photoinitiator TPOL, photoinitiator TPO, photoinitiator 184, and photoinitiator 1173. Preferably, the oil phase comprises, by weight, the following components: 40-80 parts polymerizable monomer, 2-30 parts crosslinking agent, 1-20 parts emulsifier, 0.5-5 parts stabilizer, and 0.5-5 parts initiator; Preferably, the mixing method in step (1) includes magnetic stirring; Preferably, the mixing temperature in step (1) is 25-35℃ and the mixing time is 20-40 min.

4. The preparation method according to any one of claims 1-3, characterized in that, The electrolyte includes calcium chloride and / or sodium chloride; Preferably, the initiator in the aqueous phase includes persulfate; Preferably, the persulfate includes any one or a combination of at least two of potassium persulfate, sodium persulfate, and ammonium persulfate; Preferably, based on the total mass of the aqueous phase as 100%, the content of the electrolyte is 0.5%-5%, and the content of the initiator is 0.1%-1%.

5. The preparation method according to any one of claims 1-4, characterized in that, The inner diameter of the oil phase channel in step (3) is 150-250 μm; Preferably, the inner diameter of the inner phase channel in step (3) is 80-120 μm; Preferably, the oil phase flow rate in step (3) is 50-70 μL / min; Preferably, the aqueous phase flow rate in step (3) is 120-300 μL / min; Preferably, the ratio of the oil phase flow rate to the water phase flow rate in step (3) is 1:(2-5); Preferably, the diameter of the spherical droplet in step (3) is 120-150 μm; Preferably, the inner diameter of the contraction section of the contraction-expansion channel in step (3) is 40-60 μm, the inner diameter of the expansion section is 70-90 μm, and the length is 1-3 mm; Preferably, the acceleration of the centrifuge module in step (3) is 200-400g; Preferably, the aspect ratio of the rod-shaped droplet in step (3) is (3-5):

1.

6. The preparation method according to any one of claims 1-5, characterized in that, The inner diameter of the outer sheath flow channel in step (3) is 200-400 μm; Preferably, the inner diameter of the inner eccentric channel in step (3) is 80-120 μm and the eccentricity is 50-70 μm; Preferably, in step (3), the flow velocity on the left side of the outer sheath flow channel is 140-160 μL / min and the flow velocity on the right side is 70-90 μL / min; Preferably, the flow rate of the inner eccentric channel in step (3) is 40-60 μL / min; Preferably, the aspect ratio of the ellipsoidal droplet in step (3) is (1.5-2.5):

1.

7. The preparation method according to any one of claims 1-6, characterized in that, The wavelength of the ultraviolet light used in step (4) for ultraviolet pre-curing is 300-400nm; Preferably, the UV pre-curing power in step (4) is 80-100W, and the UV pre-curing time is 15-40 seconds; Preferably, the thermosetting in step (4) is carried out in an oven; Preferably, the temperature for heat curing in step (4) is 70-90℃, and the heat curing time is 1-3h; Preferably, the post-processing in step (4) includes washing and drying.

8. A preparation method according to any one of claims 1-7, characterized in that, The preparation method includes the following steps: (1) Mix 40-80 parts of polymerizable monomer, 2-30 parts of crosslinking agent, 1-20 parts of emulsifier, 0.5-5 parts of stabilizer and 0.5-5 parts of initiator at 25-35℃ for 20-40 min to obtain oil phase; (2) Mix deionized water, electrolyte, and initiator to obtain an aqueous phase; Wherein, based on the total mass of the aqueous phase as 100%, the content of the electrolyte is 0.5%-5%, and the content of the initiator is 0.1%-1%; (3) Using a microfluidic device, the oil phase is injected into the oil phase channel of the T-shaped sheath flow microchannel. The inner diameter of the oil phase channel is 150-250 μm. The aqueous phase is injected into the inner phase channel. The inner diameter of the inner phase channel is 80-120 μm. The flow rate of the oil phase is set to 50-70 μL / min and the flow rate of the aqueous phase is set to 120-300 μL / min. The oil and aqueous phases are mixed to initially form spherical droplets with a diameter of 120-150 μm. The spherical droplets are then introduced into the contraction-expansion channel. The inner diameter of the contraction section of the contraction-expansion channel is 40-60 μm, the inner diameter of the expansion section is 70-90 μm, and the length is 1-3 mm. At the same time, the centrifugation module is started with an acceleration of 200-400 g to stretch the spherical droplets into rod-shaped droplets with an aspect ratio of (3-5):1, thus obtaining a rod-shaped high inner phase emulsion; or, Using a microfluidic device, the oil phase is injected into the outer sheath flow channel of a four-channel eccentric coaxial microchannel. The inner diameter of the outer sheath flow channel is 200-400 μm. The aqueous phase is injected into the inner eccentric channel. The inner diameter of the inner eccentric channel is 80-120 μm and the eccentricity is 50-70 μm. The flow velocity on the left side of the outer sheath flow channel is set to 140-160 μL / min, the flow velocity on the right side is set to 70-90 μL / min, and the flow velocity in the inner eccentric channel is set to 40-60 μL / min. The mixed droplets are squeezed into ellipsoidal droplets with an aspect ratio of (1.5-2.5):1 by asymmetric shear force, resulting in an ellipsoidal high internal phase emulsion. (4) After the preparation of the rod-shaped high internal phase emulsion or the ellipsoidal high internal phase emulsion, it is subjected to ultraviolet pre-curing within 0.5 seconds. The wavelength of the ultraviolet light used for ultraviolet pre-curing is 300-400nm, the power of ultraviolet pre-curing is 80-100W, and the time is 15-40 seconds. Then, it is heat-cured in an oven at 70-90℃ for 1-3 hours, washed, and dried to obtain rod-shaped porous foam material or ellipsoidal porous foam material, which is the non-spherical porous foam material.

9. A non-spherical porous foam material, characterized in that, The non-spherical porous foam material is prepared by the preparation method according to any one of claims 1-8; Preferably, the non-spherical porous foam material is a rod-shaped porous foam material or an ellipsoidal porous foam material; Preferably, the pore diameter in the rod-shaped porous foam material is 70-90 μm and the pore length is 300-350 μm; Preferably, the pore connectivity rate in the rod-shaped porous foam material is greater than 90%; Preferably, the compression modulus of the rod-shaped porous foam material is 0.5-2 MPa; Preferably, the pore diameter in the ellipsoidal porous foam material is 50-80 μm and the pore length is 90-200 μm; Preferably, the pore connectivity rate in the ellipsoidal porous foam material is greater than 90%; Preferably, the compressive modulus of the ellipsoidal porous foam material is 0.4-1.8 MPa.

10. The application of the non-spherical porous foam material as described in claim 9 in 3D cell culture, pharmaceutical dressings, and daily chemical hygiene products; Preferably, the 3D cell culture includes 3D culture of vascular endothelial cells.

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