CN113895027B

CN113895027B - Personalized knee joint local tissue partition shaping system and method based on 3D printing

Info

Publication number: CN113895027B
Application number: CN202111461100.0A
Authority: CN
Inventors: 余家阔; 许冰冰; 王星; 叶景
Original assignee: Peking University Third Hospital Peking University Third Clinical Medical College
Current assignee: Institute of Chemistry CAS; Peking University Third Hospital Peking University Third Clinical Medical College
Priority date: 2021-12-03
Filing date: 2021-12-03
Publication date: 2022-03-01
Anticipated expiration: 2041-12-03
Also published as: CN113895027A

Abstract

The invention relates to a 3D printing-based personalized knee joint local tissue partition shaping system and method, belongs to the technical field of 3D printing molds, and solves the problems that gel in a specific area cannot be formed around a tissue engineering scaffold and the shape of the gel cannot be accurately controlled in the prior art. The tissue engineering scaffold comprises a gradient tissue engineering scaffold, an outer shaping device and an inner shaping device, wherein the gradient tissue engineering scaffold is sequentially subjected to gel forming in the outer shaping device and the inner shaping device. The invention realizes the design and manufacture of the gradient porous tissue engineering scaffold, and simultaneously carries out the sectional shaping of the hydrogel containing two different growth factors by combining the two groups of clamps and shaping dies and the technology of mixing the two components into the gel, finally forms a complete scaffold structure wrapped by the hydrogel and can realize the tissue engineering reconstruction of the complex shape and multi-factor directional growth; the high customization scheme has the advantages of perfect scheme system, simple operation, small difficulty in design and manufacture and low cost.

Description

Personalized knee joint local tissue partition shaping system and method based on 3D printing

Technical Field

The invention relates to the technical field of 3D printing molds, in particular to a personalized knee joint local tissue partition shaping system and method based on 3D printing.

Background

The technology for regenerating human tissues by using 3D printing tissue engineering scaffolds does not form a large-scale market application at present, and a plurality of key technologies still remain to be solved, for example, in a meniscus tissue engineering reconstruction technology, the division and directional differentiation of stem cells is still difficult to realize at present.

The prior art can induce stem cells to differentiate into different cells by mixing solutions of two components, 4-arm-PEG-NH2-20K (4-arm-Poly (ethylene glycol)) amine-20K, 4-arm-polyethylene glycol-amino-2 ten thousand) and 4-arm-PEG-SC-20K (4-arm-Poly (ethylene glycol)) succinimidyl ester-20K, 4-arm-polyethylene glycol-succinimidyl carbonate-2 ten thousand) according to a certain proportion to form a gel, and injecting different inducing factors (CTGF and TGF-beta 3) into a specific gel area. In this technical background, since the liquid components have fluidity before being mixed, it is difficult to accurately control the position and shape of the mixing region, and thus the process and region of the gel cannot be adjusted by the conventional method.

Disclosure of Invention

In view of the foregoing analysis, the embodiments of the present invention are directed to providing a system and a method for personalized knee joint local tissue partition shaping based on 3D printing, so as to solve the problem that the prior art cannot form gel in a specific region around a tissue engineering scaffold and precisely control the shape of the gel.

In one aspect, the invention provides a 3D printing-based personalized knee joint local tissue partition shaping system, which comprises a gradient tissue engineering scaffold, an outer shaping device and an inner shaping device, wherein the gradient tissue engineering scaffold is sequentially gelatinized in the outer shaping device and the inner shaping device.

Further, moulding device in outside includes moulding anchor clamps and multistation plastic groove, gradient tissue engineering support is located in the moulding anchor clamps, will moulding anchor clamps are located multistation plastic inslot is right the injecting glue is carried out in the outside of gradient tissue engineering support.

Further, moulding anchor clamps include limiting plate and support tray, be equipped with first fixed slot on the support tray, be equipped with the second fixed slot on the limiting plate, first fixed slot with the second fixed slot sets up relatively and communicates and form jointly and place the fixed slot of gradient tissue engineering support.

Further, moulding anchor clamps are equipped with first injecting glue mouth and second injecting glue mouth, first injecting glue mouth with second injecting glue mouth all locates on the limiting plate, and with second fixed slot intercommunication.

Further, the multi-station shaping groove comprises a base station, a first arc-shaped groove is formed in the top of the base station, a shaping surface is arranged at the groove bottom of the first arc-shaped groove, and a first expansion groove and a second expansion groove are formed in the junction position of the shaping surface and the top surface of the base station.

Furthermore, a second arc-shaped groove is formed in the top of the base station, the bottom of the second arc-shaped groove is a clamp limiting surface, one side of the second arc-shaped groove is communicated with the first arc-shaped groove, and the other side of the second arc-shaped groove penetrates through the side wall of the base station; the arc-shaped surface of the bracket tray is matched with the clamp limiting surface.

Further, the inner shaping device comprises a shaping box body and a shaping top cover, and the shaping box body and the shaping top cover are detachably connected to form a drawer type structure;

the bottom surface of the moulding box body is provided with a shape following limiting ridge for limiting the gradient tissue engineering bracket, and the opening of the side wall of the moulding box body is a first limiting surface.

Further, the top of the groove body of the shaping box body is provided with a first overflow port and a second overflow port, and the bottom of the shaping box body is provided with a locking groove and communicated with the first limiting surface.

Furthermore, the shaping top cover comprises a cover plate and a shielding plate, the cover plate is covered on the box body wall of the shaping box body, and the shielding plate is attached to the first limiting surface; a third glue injection port and a fourth glue injection port are formed in the cover plate;

and a flange is arranged on the second limiting surface of the shielding plate, the second limiting surface is matched with the first limiting surface, and the flange is matched with the locking groove.

On the other hand, the invention provides a 3D printing-based personalized knee joint local tissue partition shaping method, and the 3D printing-based personalized knee joint local tissue partition shaping system is adopted and comprises the following steps:

step 1: acquiring image information of a damaged part of a patient, extracting a three-dimensional structure of the damaged part through medical image software, repairing the shape of the damaged part in modeling software, and outputting a repaired three-dimensional graph;

step 2: according to actual needs, the three-dimensional graph of the repaired local tissue is divided, different divided parts are input into 3D printing equipment, and different printing parameters are given to each divided part to realize different gap structures;

and step 3: placing the printed gradient tissue engineering scaffold in an outer shaping device according to a first shaping station to an Nth shaping station to perform outer side gluing; injecting two gel components simultaneously and synchronously along the glue injection ports and/or the expansion grooves on the two sides;

and 4, step 4: after the outer side gelatinizing is finished, taking out the gradient tissue engineering scaffold containing the outer side gel, putting the gradient tissue engineering scaffold into an inner side shaping device, synchronously and respectively injecting two components of the gel simultaneously, carrying out inner side gelatinizing, and taking out the gradient tissue engineering scaffold containing different gel components on the inner side and the outer side after the inner side gelatinizing is finished.

Compared with the prior art, the invention can realize at least one of the following beneficial effects:

(1) the invention realizes the design and manufacture of the gradient porous tissue engineering scaffold, and simultaneously carries out the sectional shaping of the hydrogel containing two different growth factors by adopting two groups of metal clamps and shaping molds printed by 3D and combining the technology of mixing two components into gel, finally forms a complete scaffold structure wrapped by the hydrogel and can realize the tissue engineering reconstruction of the complex shape and multi-factor directional growth. The high customization scheme has the advantages of perfect scheme system, simple operation, small difficulty in design and manufacture and low cost.

(2) The simultaneous and simultaneous injection of the two components of the gel of the present invention is intended to ensure that the two components can be injected according to a ratio of 1: 1, fully mixing; the injection process is from top to bottom, and the solidification process is from bottom to top, so that the liquid level height can be well controlled while the gradient tissue engineering scaffold is fully infiltrated.

(3) The multi-station plastic groove is provided with the overflow groove, the liquid level height of the hydrogel solution is observed through the gap by naked eyes, the glue injection can be stopped when the liquid level height of the hydrogel solution reaches the position flush with the bottom of the overflow groove, and the glue injection does not need to be stopped when the hydrogel solution overflows, so that the material is saved; the overflow groove also has the function of limiting the height of the liquid level of the hydrogel solution to a preset dividing surface of the gradient tissue engineering scaffold, and accurately controlling the position of the subarea of the gradient tissue engineering scaffold.

(4) According to the invention, under the shaping station, the transverse limit stop is inserted into the limit groove to limit the transverse displacement of the shaping fixture, one side of the transverse limit stop is attached to the baffle, and the other side of the transverse limit stop has a gap with the bracket tray bracket, so that the shaping fixture can move for a certain distance along the transverse direction after the gelling process is finished, the gel can be smoothly stripped from the wall surface of the groove wall, and then the shaping fixture is vertically moved out, so that the gel can be smoothly stripped from the shaping surface.

In the invention, the technical schemes can be combined with each other to realize more preferable combination schemes. Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and drawings.

Drawings

The drawings are only for purposes of illustrating particular embodiments and are not to be construed as limiting the invention, wherein like reference numerals are used to designate like parts throughout.

FIG. 1 is a schematic structural diagram of a gradient tissue engineering scaffold according to an embodiment;

FIG. 2 is a schematic view of an embodiment of an installation of an outside molding device and a gradient tissue engineering scaffold;

FIG. 3 is a schematic view of an embodiment of an installation of an internal shaping device and a gradient tissue engineering scaffold;

FIG. 4 is a schematic diagram of an embodiment of an outside molding configuration;

FIG. 5 is a schematic diagram of a shaping jig according to an embodiment;

FIG. 6 is a schematic view of a molding jig and a gradient tissue engineering scaffold installation according to an embodiment;

FIG. 7 is a schematic diagram of a multi-station plastic-shaped groove structure according to an embodiment;

FIG. 8 is a schematic view of a first shaping station state according to an embodiment;

FIG. 9 is a schematic view of a second shaping station according to an embodiment;

FIG. 10 is a schematic view of a third molding station according to an embodiment;

FIG. 11 is a sectional view A-A taken at a second shaping station according to an exemplary embodiment;

FIG. 12 is a rear view of a second shaping station of an embodiment;

FIG. 13 is a schematic view of an embodiment of an inside shaping device;

fig. 14 is an exploded view of an embodiment of an inside shaping device;

FIG. 15 is a schematic diagram of a molding box according to an embodiment;

fig. 16 is a schematic view of a shaped top cover structure according to an embodiment.

Reference numerals:

100. a gradient tissue engineering scaffold; 200. an outer shaping device; 210. shaping a clamp; 211. a limiting plate; 211-1, a first station limiting plate; 211-2 and a second station limiting plate; 211-3, a third station limiting plate; 212. a rack tray; 213. a limiting groove; 214. a baffle plate; 215-1, a first glue injection port; 215-2 and a second glue injection port; 220. multi-station plastic grooves; 221. a base station; 222. a trench wall; 223. an overflow trough; 224. molding surface; 225-1, a first expansion slot; 225-2, a second expansion slot; 226. a clamp limiting surface; 227. a transverse limit stop; 230. a plastic cavity; 218. an arc-shaped surface; 216. a first fixing groove; 217. a second fixing groove; 300. an inside shaping device; 310. shaping a box body; 311-1, a first overflow port; 311-2, a second overflow port; 312. the wall surface of the box body; 313. the bottom surface of the box body; 314. a conformal limiting ridge; 315. a first limiting surface; 316. locking the groove; 320. shaping a top cover; 321-1 and a third glue injection port; 321-2 and a fourth glue injection port; 322. air holes are formed; 323. a cover plate; 324. a second limiting surface; 325. a flange; 326-1, a third overflow port; 326-2 and a fourth overflow port.

Detailed Description

The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings, which form a part hereof, and which together with the embodiments of the invention serve to explain the principles of the invention and not to limit its scope.

In the description of the embodiments of the present invention, it should be noted that the term "connected" is to be understood broadly, and may be, for example, fixed, detachable, or integrally connected, and may be mechanically or electrically connected, and may be directly or indirectly connected through an intermediate medium, unless otherwise specifically stated or limited. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.

The terms "top," "bottom," "above … …," "below," and "on … …" as used throughout the description are relative positions with respect to components of the device, such as the relative positions of the top and bottom substrates inside the device. It will be appreciated that the devices are multifunctional, regardless of their orientation in space.

Example 1

One embodiment of the invention, as shown in fig. 1-3, discloses a personalized knee joint local tissue partition shaping system based on 3D printing, which comprises a gradient tissue engineering scaffold 100, an outer shaping device 200 and an inner shaping device 300, wherein the gradient tissue engineering scaffold 100 is sequentially gelatinized in the outer shaping device 200 and the inner shaping device 300.

In this embodiment, the 3D printing material of the outer shaping device 200 and the inner shaping device 300 is metal.

The gradient tissue engineering scaffold 100 is a gradient porous loose structure, is designed according to the tissue morphology of a specific region of a patient and is processed by a biomaterial through a 3D printing technology, and the biomaterial is preferably a polycaprolactone material which can be degraded in vivo.

When the meniscus tissue is taken as a typical example, the synovial border region (namely, the outer side of the meniscus tissue) of the gradient tissue engineering scaffold 100 has small fiber density and large pore diameter, and the average pore diameter of the synovial border region is 400-500 μm; the free limbal region of the gradient tissue engineering scaffold 100 (i.e., the inner edge of the meniscus tissue) has a high confinement density and a small pore size, with the mean pore size of the free limbal region being about 200 μm. The two pore diameters each account for half the width of the stent.

The heterogeneous tissue engineering meniscus can be constructed by the gradient porous tissue engineering scaffold. In combination with the 3D printing meniscus scaffold composite hydrogel-mold (the outer shaping device 200 and the inner shaping device 300 in this embodiment), it is possible to achieve zonal release of CTGF (Connective Tissue Growth Factor) and TGF- β 3 (Transforming Growth Factor- β 3) (CTGF and TGF- β 3 induce differentiation of mesenchymal stem cells and express regional specific type I collagen and type II collagen, respectively).

It should be noted that the shape of the gradient tissue engineering scaffold 100 is not limited, and the specific shape thereof is designed according to the tissue morphology of the specific region of the patient, and the present embodiment is described by taking meniscal tissue as an example.

As shown in fig. 2, the outer shaping device 200 includes a shaping fixture 210 and a multi-station shaping groove 220, and the shaping fixture 210 is disposed in the multi-station shaping groove 220 to inject the glue to the outer side of the gradient tissue engineering scaffold 100.

As shown in fig. 4 and 5, the shaping jig 210 includes a limiting plate 211, a bracket tray 212, and a baffle 214, the bracket tray 212 and the baffle 214 are parallel to each other, and a side plane of the limiting plate 211 is parallel to the bracket tray 212 and the baffle 214. The limiting plate 211 is arranged above the bracket tray 212, the bracket tray 212 is arranged above the baffle 214, one end of the limiting plate 211 is connected with the bracket tray 212, the other end of the limiting plate is suspended, the bracket tray 212 is connected with the baffle 214, and a limiting groove 213 is arranged between the bracket tray 212 and the baffle 214.

In a preferred embodiment, the support tray 212 and the baffle 214 are both disc-shaped structures defined by an arc-shaped surface and a plane, the support tray 212 and the baffle 214 are identical in shape, only the thickness of the support tray 212 and the thickness of the baffle 214 are different, and preferably, the thickness of the support tray 212 is greater than the thickness of the baffle 214. After the bracket tray 212 and the baffle 214 are connected on the plane side, a limiting groove 213 is left at the arc-shaped surface.

Further, as shown in fig. 2 and 4, the planar sides of the bracket tray 212 and the baffle 214 are provided with grooves, the grooves are similar to U-shape, the opening width of the grooves is larger than the bottom width of the grooves, and the grooves are communicated with the lateral plane of the limit plate 211.

In this embodiment, the limiting plate 211, the bracket tray 212, and the baffle 214 are integrally formed.

In other words, the shaping jig 210 includes a limiting plate 211 and a bracket stopper, the bracket stopper is a disc-shaped structure defined by an arc-shaped surface and a plane, one end of the limiting plate 211 is connected with the plane side of the bracket stopper, and the end surface of the limiting plate 211 is flush with the plane of the bracket stopper, and the other end of the limiting plate 211 is suspended at one side of the bracket stopper. A limiting groove 213 is formed along the circumferential direction of the arc-shaped surface of the bracket stop block, and the bracket stop block is divided into two parts, namely a bracket tray 212 and a baffle plate 214 by the limiting groove 213. Preferably, the thickness of the rack tray 212 is greater than the thickness of the baffle 214.

Further, the plane side of support dog is equipped with the recess, and the recess is similar to the U-shaped, and the opening width of recess is greater than its bottom width, and the recess communicates with limiting plate 211 for also form the structure of similar U-shaped recess on the limiting plate 211.

In this embodiment, be equipped with type U-shaped groove on moulding anchor clamps 210, effectively alleviateed moulding anchor clamps 210's weight, reduced the use of material simultaneously, improved the efficiency that adopts 3D to print moulding anchor clamps 210.

In order to facilitate glue injection to the gradient tissue engineering scaffold 100, as shown in fig. 4, the shaping fixture 210 is further provided with a first glue injection port 215-1 and a second glue injection port 215-2, and both the first glue injection port 215-1 and the second glue injection port 215-2 are disposed on the limiting plate 211. Specifically, the first glue injection port 215-1 and the second glue injection port 215-2 are disposed at the end of the limiting portion 211 for connecting the bracket tray 212, and are located at two sides of the similar U-shaped groove.

In order to place the gradient tissue engineering scaffold 100, as shown in fig. 4 and 5, the shaping jig 210 is further provided with a first fixing groove 216 and a second fixing groove 217, the first fixing groove 216 is disposed on the scaffold tray 212, the second fixing groove 217 is disposed on the position-limiting plate 211, the first fixing groove 216 and the second fixing groove 217 are disposed opposite to each other and are communicated with each other, and the first fixing groove 216 and the second fixing groove 217 together form a fixing groove for placing the gradient tissue engineering scaffold 100. The shape of the fixation groove is adapted to the gradient tissue engineering scaffold 100.

As shown in fig. 4, the first glue injection hole 215-1 and the second glue injection hole 215-2 are both communicated with the second fixing groove 217, and thus the hydrogel solution injected from the first glue injection hole 215-1 and the second glue injection hole 215-2 can smoothly flow into the second fixing groove 217 and infiltrate the gradient tissue engineering scaffold 100.

In this embodiment, in order to adapt to the meniscus-shaped gradient tissue engineering scaffold 100 shown in fig. 1, the first fixing groove 216 and the second fixing groove 217 are both designed to be half-moon-shaped, and the free end of the position-limiting plate 211 is located above the first fixing groove 216. After the gradient tissue engineering scaffold 100 is disposed in the first fixing groove 216, the second fixing groove 217 of the limiting plate 211 just presses and buckles the edge structure of the gradient tissue engineering scaffold 100, so as to have a certain limiting and clamping effect on the gradient tissue engineering scaffold 100.

Since the gradient tissue engineering scaffold 100 is not injected with glue in one state, a plurality of molding stations, preferably 3 molding stations, are formed by the molding jig 210 and the multi-station molding groove 220. In order to cooperate with the multi-station glue injection of the gradient tissue engineering scaffold 100, as shown in fig. 5 and 6, the limiting plate 211 comprises a first station limiting plate 211-1, a second station limiting plate 211-2 and a third station limiting plate 211-3, and the first station limiting plate 211-1, the second station limiting plate 211-2 and the third station limiting plate 211-3 are respectively attached to the groove wall of the multi-station plastic groove 220 under the first molding station, the second molding station and the third molding station to limit the transverse movement of the multi-station plastic fixture 210.

It should be noted that, the U-shaped groove side of the limiting plate 211 is defined as an inner edge, and after the shaping jig 210 is placed on the multi-station shaping groove 220, as shown in fig. 8, the outer edge of the first station limiting plate 211-1 is in a horizontal state and is a first shaping station; as shown in fig. 9, the second shaping station is set when the outer edge of the second station limiting plate 211-2 is horizontal; as shown in fig. 10, the third shaping station is set when the outer edge of the third station-defining plate 211-3 is horizontal.

In this embodiment, the first station limiting plate 211-1, the second station limiting plate 211-2 and the third station limiting plate 211-3 are sequentially connected, the first station limiting plate 211-1 and the third station limiting plate 211-3 are two side walls similar to a U-shaped groove, and the second station limiting plate 211-2 is a groove bottom similar to the U-shaped groove.

As shown in fig. 7, the multi-station plastic groove 220 includes a base platform 221, the base platform 221 is a rectangular parallelepiped structure, a first arc-shaped groove is disposed at the top of the base platform 221, a plastic surface 224 is disposed at the bottom of the first arc-shaped groove, in order to facilitate glue injection and infiltration of the gradient tissue engineering scaffold 100 in each molding station state, a first expansion groove 225-1 and a second expansion groove 225-2 are disposed at a boundary position between the plastic surface 224 and the top surface of the base platform 221, and both the first expansion groove 225-1 and the second expansion groove 225-2 are glue injection opening expansion grooves. Preferably, the first and second expansion slots 225-1 and 225-2 are smoothly transitioned with the shaping surface 224.

The first arc-shaped groove and the side surface of the base platform 221 form a groove wall 222, and the inner side of the groove wall 222 is attached to the side plane of the limiting plate 211 to limit the transverse movement of the shaping fixture 210.

Considering that excessive hydrogel solution exists in the glue injection process, the groove wall 222 is provided with an overflow groove 223, the bottom of the overflow groove 223 is slightly lower than the outer edge of the limiting plate 211 at the lower shaping station, so that a gap exists between the bottom of the overflow groove 223 and the outer edge of the limiting plate 211 at the lower shaping station, that is, the limiting plate 211 does not completely shield the overflow groove 223 at the lower shaping station, preferably, the overflow groove 223 penetrates through the top of the base 221, and the overflow groove 223 is located in the middle of the groove wall 222.

In this embodiment, when the limiting plate 211 is located different shaping stations, the limiting plate 211 partially shields the overflow groove 223, and during the glue injection process, the excess hydrogel solution can overflow from the overflow groove 223. Meanwhile, the stop time of glue injection can be judged through the overflow groove 223, and when the gel solution overflows from the overflow groove 223, glue injection is stopped immediately. Meanwhile, because a gap exists between the overflow groove 223 and the outer edge of the limiting plate 211, the height of the liquid level of the hydrogel solution can be observed through the gap by naked eyes, when the height of the liquid level of the hydrogel solution reaches the position flush with the bottom of the overflow groove 223, glue injection can be stopped, and the glue injection can be stopped without waiting for the overflow of the hydrogel solution, so that the material is saved. The overflow groove 223 also functions to limit the height of the liquid level of the hydrogel solution to a preset dividing plane of the gradient tissue engineering scaffold 100, and precisely control the position of the partition of the gradient tissue engineering scaffold 100. In this embodiment, the preset dividing plane of the gradient tissue engineering scaffold 100 is such that the inner side and the outer side of the gradient tissue engineering scaffold 100 are respectively half.

In order to place the shaping fixture 210, as shown in fig. 7, a second arc-shaped groove is disposed at the top of the base platform 221, a fixture limiting surface 226 is disposed at the bottom of the second arc-shaped groove, the second arc-shaped groove and the first arc-shaped groove are arranged in parallel, the second arc-shaped groove is deeper than the first arc-shaped groove, one side of the second arc-shaped groove is communicated with the first arc-shaped groove, and the other side of the second arc-shaped groove penetrates through the side wall of the base platform 221.

In order to limit the lateral movement of the shaping jig 210, as shown in fig. 7, a lateral limit stopper 227 is disposed on the jig limiting surface 226, the lateral limit stopper 227 cooperates with the limiting groove 213 to limit the shaping jig 210, the thickness of the lateral limit stopper 227 is smaller than the width of the limiting groove 213, and the height of the lateral limit stopper 227 is not greater than the depth of the limiting groove 213.

When the shaping fixture 210 is arranged on the multi-station plastic groove 220, the arc surface 218 of the bracket tray 212 is in contact with the fixture limiting surface 226, the transverse limiting stopper 227 is arranged in the limiting groove 213 and attached to the baffle 214, a half-opening shape (i.e., a half-moon-shaped fixing groove formed by the first fixing groove 216 and the second fixing groove 217) with a C-shaped cross section is formed between the bracket tray 212 and the limiting plate 211, so that the gradient tissue engineering bracket 100 can be conveniently placed, and the groove wall 222 is used for limiting the gradient tissue engineering bracket 100, so that the gradient tissue engineering bracket 100 does not slide at a shaping station.

As shown in fig. 11 and 12, in the shaping station, the shaping fixture 210 supports the gradient tissue engineering scaffold 100 and keeps the scaffold tray 212 vertical, at this time, the arc surface 218 of the scaffold tray 212 is tightly attached to the position-limiting surface 226, and the outer edge surface (i.e., the arc surface 218) of the scaffold tray 212 is in accordance with the shape of the position-limiting surface 226. Under the structure, the shaping clamp 210 and the multi-station shaping groove 220 form a shaping cavity 230 around the gradient tissue engineering scaffold 100, and the shaping cavity 230 is used for mixing different liquid components into glue.

It should be noted that three different shaping stations form three different shaping cavities 230.

As shown in fig. 11, at the shaping station, the horizontal limit stopper 227 is inserted into the limit groove 213 for limiting the horizontal displacement of the shaping jig 210, one side of the horizontal limit stopper 227 is attached to the baffle 214, and the other side of the horizontal limit stopper has a gap with the bracket of the bracket tray 212, so that the shaping jig 210 moves a distance in the horizontal direction after the gelling process is finished, the gel is smoothly peeled off from the wall surface of the groove wall 222, and then the shaping jig 210 is vertically moved out, so that the gel is smoothly peeled off from the shaping surface 224.

When glue injection is performed on the gradient tissue engineering scaffold 100, a proper glue injection port is selected according to the placement station of the gradient tissue engineering scaffold 100. Preferably, when the shaping jig 210 is located at the first shaping station, the first glue injection port 215-1, the first expansion slot 225-1 and the second expansion slot 225-2 are selected for injecting glue; when the shaping fixture 210 is located at the second shaping station, selecting the first expansion groove 225-1 and the second expansion groove 225-2 for injecting glue; when the shaping jig 210 is located at the third shaping station, the second glue injection port 215-2, the first expansion slot 225-1 and the second expansion slot 225-2 are selected for glue injection.

As shown in fig. 3, 13 and 14, the inner shaping device 300 includes a shaping box 310 and a shaping cap 320, and the shaping box 310 and the shaping cap 320 are detachably connected to form a drawer structure.

As shown in fig. 15, the shaping box 310 is a semi-open trough structure, and the shaping box 310 includes a box wall and a box bottom, preferably, the box wall is a non-closed arc, the box bottom is a flat plate, and the box bottom closes one end of the box wall, so that the shaping box 310 forms a semi-open trough structure with an open end and an open side wall. The opening of the side wall of the shaping box 310 is a first limiting surface 315, and preferably, the first limiting surface 315 is a plane.

In order to facilitate peeling of the trapezoid tissue engineering scaffold 100 after glue injection, in the inner cavity of the shaping box body 310, the box body wall surface 312 and the box body bottom surface 313 are both smooth and clean surfaces. For positioning the trapezoid tissue engineering scaffold 100, as shown in fig. 15, the bottom surface 313 of the box body is provided with a conformal limiting ridge 314, and when the trapezoid tissue engineering scaffold 100 is placed, the conformal limiting ridge 314 is completely attached to the inner side edge of the trapezoid tissue engineering scaffold 100, and the surface mounting position is accurate.

In this embodiment, in order to fit the half-moon-shaped trapezoidal tissue engineering scaffold 100, the box wall 312 and the conformal limiting ridge 314 are both half-moon-shaped, and the conformal limiting ridge 314 fits with the inner edge of the half-moon-shaped trapezoidal tissue engineering scaffold 100. Note that the meniscus-like depression side is the inner side, and the convex side is the outer side.

In order to facilitate overflow of the excess hydrogel solution during the glue injection process, as shown in fig. 15, an overflow port is formed at the top of the tank body of the shaping box body 310, and the overflow port includes a first overflow port 311-1 and a second overflow port 311-2, that is, a groove is dug at the top of the box body wall to form an overflow port. Preferably, the first overflow port 311-1 and the second overflow port 311-2 are disposed near the first stopper surface 315.

In order to form a sliding-slot type position-limiting locking structure with the shaping top cover 320, as shown in fig. 14, the bottom of the shaping box 310 is provided with a locking groove 316, and is communicated with the first position-limiting surface 315. Preferably, the locking groove 316 is a rectangular groove, and the side walls of the locking groove 316 are rounded.

As shown in fig. 16, the shaping top cover 320 includes a cover plate 323 and a shielding plate, the shielding plate is disposed on one side of the cover plate 323, the cover plate 323 is used to cover the box wall of the shaping box 310, and the shielding plate is used to shield the first limiting surface 315 of the shaping box 310. With this configuration, the shaping cap 320 covers the end opening and the side wall opening of the shaping box 310, which form a drawer-type structure.

In order to further limit the position of the trapezoidal tissue engineering scaffold 100 arranged in the shaping box 310, as shown in fig. 16, a boss is arranged on the inner side of the cover plate 323, preferably, the boss is a truncated cone, the large bottom surface of the truncated cone is connected with the cover plate 323, and the truncated cone-shaped boss structure is matched with the groove side of the half-moon-shaped trapezoidal tissue engineering scaffold 100.

As shown in fig. 13 and 16, the cover plate 323 is provided with a third glue injection port 321-1 and a fourth glue injection port 321-2, the third glue injection port 321-1 and the fourth glue injection port 321-2 are disposed on two sides of the boss, and preferably, the third glue injection port 321-1 and the fourth glue injection port 321-2 are disposed at a boundary edge between the boss and the cover plate 323 and are disposed close to the shielding plate.

Considering that the excess hydrogel solution needs to overflow during the glue injection process, as shown in fig. 16, the cover plate 323 is provided with a third overflow port 326-1 and a fourth overflow port 326-2, the third overflow port 326-1 and the fourth overflow port 326-2 are respectively disposed at two sides of the boss, and the third overflow port 326-1 and the fourth overflow port 326-2 respectively correspond to the first overflow port 311-1 and the second overflow port 311-2. As shown in FIG. 13, when the plastic top cover 320 is covered on the plastic box 310, the first overflow opening 311-1 and the third overflow opening 326-1 form an overflow opening, and the second overflow opening 311-2 and the fourth overflow opening 326-2 form an overflow opening.

In order to form a sliding-slot type position-limiting locking structure with the shaping box body 310, as shown in fig. 14 and 16, a flange 325 is disposed on the second limiting surface 324 of the shielding plate, the second limiting surface 324 is matched with the first limiting surface 315, and when the shaping box body 310 and the shaping top cover 320 are assembled, the first limiting surface 315 and the second limiting surface 324 are tightly attached. The flange 325 mates with the locking groove 316, the flange 325 being the same size and shape as the locking groove 316. Preferably, the flange 325 is a rectangular parallelepiped, and the side surfaces of the flange 325 are rounded. When the shaped top cover 320 is assembled with the shaped box 310, the bottom surface of the flange 325 is flush with the bottom surface of the trough bottom.

In this embodiment, the flange 325 is engaged with the locking groove 316, so that the plastic top cover 320 can be aligned more conveniently when closed, and the plastic top cover has a locking function and is also easy to detach. It should be noted that the contact surface between the flange 325 and the locking groove 316 is reserved 0.05-0.1 mm.

Considering that the gradient tissue engineering scaffold 100 needs to be ventilated when performing inner-side injection molding, as shown in fig. 16, a plurality of ventilation holes 322 are further formed in the cover plate 323, and the ventilation holes 322 are formed along the boundary edge between the boss and the cover plate 323.

Compared with the prior art, the design and the manufacture of the gradient porous tissue engineering scaffold are realized based on the personalized design method and by combining the 3D printing technology, meanwhile, the hydrogel containing two different growth factors is shaped in a partition mode through two groups of clamps and shaping molds and combining the technology of mixing the two components into the gel, and finally, a complete scaffold structure wrapped by the hydrogel is formed, so that the tissue engineering reconstruction of complex-shaped multi-factor oriented growth can be realized. The high customization scheme has the advantages of perfect scheme system, simple operation, small difficulty in design and manufacture and low cost.

Example 2

A specific embodiment of the present invention, as shown in fig. 1 to 16, discloses a 3D printing-based personalized knee joint local tissue partition shaping method, and the 3D printing-based personalized knee joint local tissue partition shaping system of embodiment 1 is adopted, and includes the steps of:

s1: image information of a damaged part of a patient is acquired through technologies such as Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), illustratively, a three-dimensional structure of the damaged part of a meniscus tissue is extracted through medical image software, the shape of the damaged part is repaired in modeling software, and a repaired three-dimensional graph is output.

S2: according to actual needs, the three-dimensional graph of the repaired local tissue is divided, different divided parts are input into 3D printing equipment, and different printing parameters are given to all parts to realize different void structures. Illustratively, a meniscus-shaped gradient tissue engineering scaffold 100.

S3: after the gradient tissue engineering scaffold 100 (tissue engineering scaffold with personalized gradient porous structure) is printed out, the gradient tissue engineering scaffold 100 is placed at a corresponding position of an outer shaping device, and the outer side of the gradient tissue engineering scaffold 100 is gelatinized.

It should be noted that the outer-side gel forming is sequentially arranged from the first shaping station to the nth shaping station, the operation of the next shaping station can be performed only after the gel is solidified sufficiently under each shaping station, and two components of the gel are simultaneously and respectively injected along the glue injection ports and/or the expansion grooves on the two sides of the gel during the glue injection at each time.

The shaping jig 210 and the multi-station shaping groove 220 cooperate to form N shaping stations, N being preferably 3.

S4: after the outer side gel forming is completed, the gradient tissue engineering scaffold 100 (containing the outer side gel) is taken out and placed in a position corresponding to the shaping box body 310, the shaping top cover 320 is closed, and two gel components are simultaneously and synchronously injected into the shaping top cover 320 along the two gel injection ports (the third gel injection port 321-1 and the fourth gel injection port 321-2).

It should be noted that the simultaneous injection of the two components of the gel is intended to ensure that the two components can be injected according to a ratio of 1: 1, and mixing well. The injection process is from top to bottom and the coagulation process is from bottom to top, thus ensuring that the gradient tissue engineering scaffold 100 is fully infiltrated and the liquid level is well controlled.

S5: and (3) after the gel is completely solidified, removing the shaping top cover 320, and taking out the gradient tissue engineering scaffold 100 (at the moment, the gradient tissue engineering scaffold 100 contains different gel components on the inner side and the outer side).

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.

Claims

1. A personalized knee joint local tissue partition shaping system based on 3D printing is characterized by comprising a gradient tissue engineering scaffold (100), an outer shaping device (200) and an inner shaping device (300), wherein the gradient tissue engineering scaffold (100) is sequentially gelatinized in the outer shaping device (200) and the inner shaping device (300); moulding device in the outside (200) is including moulding anchor clamps (210), moulding anchor clamps (210) are including limiting plate (211) and support tray (212), be equipped with first fixed slot (216) on support tray (212), be equipped with second fixed slot (217) on limiting plate (211), first fixed slot (216) with second fixed slot (217) set up relatively and the intercommunication forms jointly and places the fixed slot of gradient tissue engineering support (100).

2. The system for 3D printing based personalized knee joint local tissue partition shaping according to claim 1, wherein the outer shaping device (200) further comprises a multi-station shaping groove (220), the gradient tissue engineering scaffold (100) is arranged in the shaping fixture (210), and the shaping fixture (210) is arranged in the multi-station shaping groove (220) for injecting glue to the outer side of the gradient tissue engineering scaffold (100).

3. The 3D printing-based personalized knee joint local tissue partition shaping system according to claim 1, wherein the shaping fixture (210) is provided with a first glue injection port (215-1) and a second glue injection port (215-2), and the first glue injection port (215-1) and the second glue injection port (215-2) are both arranged on the limiting plate (211) and are communicated with the second fixing groove (217).

4. The 3D printing-based personalized knee joint local tissue partition shaping system according to claim 2, wherein the multi-station shaping groove (220) comprises a base platform (221), the top of the base platform (221) is provided with a first arc-shaped groove, the bottom of the first arc-shaped groove is provided with a shaping surface (224), and the intersection position of the shaping surface (224) and the top surface of the base platform (221) is provided with a first expansion groove (225-1) and a second expansion groove (225-2).

5. The 3D printing personalized knee joint local tissue partition shaping system according to claim 4, wherein a second arc-shaped groove is formed in the top of the abutment (221), a groove bottom of the second arc-shaped groove is a clamp limiting surface (226), one side of the second arc-shaped groove is communicated with the first arc-shaped groove, and the other side of the second arc-shaped groove penetrates through the side wall of the abutment (221); the arc-shaped surface (218) of the bracket tray (212) is matched with the clamp limiting surface (226).

6. The 3D printing-based personalized knee joint local tissue zoning shaping system according to any one of claims 1-5, wherein the medial shaping device (300) comprises a shaping box (310) and a shaping top cover (320), and the shaping box (310) and the shaping top cover (320) are detachably connected to form a drawer-type structure;

the shape-following limiting ridge (314) used for limiting the gradient tissue engineering bracket (100) is arranged on the bottom surface (313) of the shaping box body (310), and a first limiting surface (315) is arranged at the opening of the side wall of the shaping box body (310).

7. The personalized knee joint local tissue zoning and shaping system based on 3D printing according to claim 6, wherein a first overflow port (311-1) and a second overflow port (311-2) are formed in the top of a groove body of the shaping box body (310), and a locking groove (316) is formed in the bottom of the shaping box body (310) and is communicated with the first limiting surface (315).

8. The 3D printing personalized knee joint local tissue partition shaping system according to claim 7, wherein the shaping top cover (320) comprises a cover plate (323) and a shielding plate, the cover plate (323) covers the box body wall of the shaping box body (310), and the shielding plate is attached to the first limiting surface (315); a third glue injection port (321-1) and a fourth glue injection port (321-2) are formed in the cover plate (323);

a flange (325) is arranged on the second limiting surface (324) of the shielding plate, the second limiting surface (324) is matched with the first limiting surface (315), and the flange (325) is matched with the locking groove (316).

9. A3D printing-based personalized knee joint local tissue partition shaping method is characterized in that the 3D printing-based personalized knee joint local tissue partition shaping system of any one of claims 1-8 is adopted, and the steps comprise:

and step 3: placing the printed gradient tissue engineering scaffold (100) in an outer shaping device (200) according to a first shaping station to an Nth shaping station to perform outer side gluing;

and 4, step 4: after the outer side gelatinizing is finished, taking out the gradient tissue engineering scaffold (100) containing the outer side gel, putting the gradient tissue engineering scaffold into an inner side shaping device (300) for inner side gelatinizing, and taking out the gradient tissue engineering scaffold (100) containing different gel components on the inner side and the outer side after the inner side gelatinizing is finished.