Manufacturing method of microgel stent based on flexible mold capillary folding technology

A flexible mold and manufacturing method technology, applied in biochemical equipment and methods, cell culture supports/coatings, microorganisms, etc., can solve the problems of difficult to form three-dimensional microgel scaffolds, difficult to control scaffold morphology and other problems

Active Publication Date: 2020-04-24

XI AN JIAOTONG UNIV

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Problems solved by technology

However, these methods are difficult to control the morphology of scaffolds. For example, microfluidic technology can only prepare spherical or nearly spherical scaffolds. Photolithography and traditional mol...

Abstract

A manufacturing method of a microgel stent based on a flexible mold capillary folding technology comprises the following steps: firstly, a flexible mold is designed, then the flexible mold is prepared, a microgel stent is prepared, and a grabbing structure of the flexible mold is in contact with the liquid level of hydrogel so that the hydrogel will wet the surface of the grabbing structure and capillary force is automatically generated at a contact line position; subsequently, the flexible mold is gradually pulled away from the liquid level of the hydrogel, the grabbing structure is graduallybent and deformed until the grabbing structure is finally closed under the action of capillary force, the hydrogel is wrapped in a formed cavity, and then the hydrogel is cross-linked and cured; andfinally, demolding of the microgel stent is conducted, the flexible mold and the hydrogel are immersed in water, water molecules infiltrate the interface of the grabbing structure and the hydrogel anddestroy the binding force between the grabbing structure and the hydrogel, the grabbing structure is automatically opened, and the hydrogel automatically falls off. According to the invention, controllable manufacturing of micron-scale hydrogel stents with different morphologies can be realized.

Application Domain

Cell culture supports/coatingProsthesis

Technology Topic

Biomedical engineeringNanotechnology +2

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Experimental program(1)

Example Embodiment

[0021] The present invention will be described in detail below in conjunction with the drawings and embodiments.

[0022] A method for manufacturing a microgel scaffold based on flexible mold capillary folding technology includes the following steps:

[0023] 1) Design of flexible mold: In order to prepare microgel scaffolds with different morphologies, the shape of the flexible mold is optimized by using topology knowledge. The flexible mold includes a flexible matrix, and one side of the flexible matrix is equipped with periodic grabbing Structure: Expanding the outer surface of the designed microgel scaffold to a two-dimensional plane is the shape of the flexible mold;

[0024] 2) Preparation of flexible mold:

[0025] 2.1) Spin-coating the first layer of photoresist 2 on the silicon wafer or glass wafer 1, its thickness h 1 It is micron scale, and then baked on the hot plate; the top ultraviolet light 4 passes through the first reticle 3 for exposure. The reticle 3 is a periodic structure, and the light-transmitting area w in each cycle 1 And the opaque area w 2 All are micron level, such as Picture 1-1 Shown

[0026] 2.2) Spin coating the second layer of photoresist 5, photoresist thickness h 2 For the micron level, the top ultraviolet light 4 passes through the second mask 6 for the second exposure after the pre-baking, and the unexposed area width w 3 , The width of the exposure area w 4 , Are all micron level, such as Figure 1-2 Shown

[0027] 2.3) Use a developer to develop the photoresist to obtain a photoresist mold, such as Figure 1-3 Shown

[0028] 2.4) Pour flexible material (such as PDMS) into the photoresist mold, the thickness of the flexible material h 3 For the micron level, the flexible material is cured by vacuuming and heating in a vacuum oven, such as Figure 1-4 Shown

[0029] 2.5) The photoresist is removed, and the flexible mold 7 is prepared. The flexible mold 7 includes a flexible substrate 701. One side of the flexible substrate 701 is provided with a periodic grasping structure 702, such as Figure 1-5 Shown

[0030] Step 3) Preparation of microgel scaffold: prepare a hydrogel, and place the gripping structure 702 of the flexible mold 7 close to the liquid surface of the hydrogel 8 to ensure that the two are in contact. The width of the joint between the gripping structure 702 and the flexible substrate 701 w 5 And height h 3 , The width w of the grab structure 702 6 , The maximum width w between the grabbing structures 702 7 , The minimum width w 8 For the micron level, such as diagram 2-1 As shown; then the flexible mold 7 is lifted upwards, the gripping structure 702 of the flexible mold 7 is bent and deformed under the action of capillary force, until it is completely folded to form a closed three-dimensional cavity 9, and the hydrogel 8 is wrapped in it. Gel 8 particles high h 4 , Width w 9 For the micrometer scale, such Figure 2-2 As shown; according to the different types of hydrogels 8, UV light 4 or temperature crosslinking, such as Figure 2-3 Shown

[0031] Step 4) Demoulding of the microgel stent: After the hydrogel 8 is cross-linked and solidified, the flexible mold 7 and the hydrogel 8 are immersed in the water 10, and the water molecules infiltrate the grasping structure of the hydrogel 8 and the flexible mold 7 The 702 interface eliminates the binding force between the two interfaces, thereby realizing automatic demoulding of the microgel stent 11, such as image 3 Shown.

[0032] The shape of the microgel support 11 depends on the shape of the grasping structure 702 of the flexible mold 7. By preparing the grasping structure 702 of different shapes, the microgel support 11 with different shapes can be obtained. For example, the grasping structure 702 may be a triangular flexible mold 12, a four-pointed star-shaped flexible mold 14, a cross-shaped flexible mold 16, a rectangular flexible mold 18, and a petal-shaped flexible mold 20, and the microgel support 11 that can be prepared is a tetrahedral microaggregate. Plastic bracket 13, pentahedral bracket 15, hexahedral bracket 17, cylindrical bracket 19 and spherical bracket 21, such as Figure 4 Shown. The prepared microgel scaffold can be used for cell culture in vitro, and cells cultured on scaffolds with different shapes have different differentiation capabilities and biological functions.

[0033] The present invention proposes a capillary folding technology based on a flexible mold, which uses surface tension to drive the gripping structure of the flexible mold to bend and deform to realize the folding and closing of the flexible mold and the filling of the hydrogel, and the hydrogel is crosslinked and cured, and then The flexible mold is immersed in water to release the hydrogel. The invention can be used for the manufacture of microgel stents, and microgel stents with different shapes can be formed by preparing flexible molds of different shapes.

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