WO2024051013A1 - 组织工程支架的打印方法、打印系统、终端及存储介质 - Google Patents

组织工程支架的打印方法、打印系统、终端及存储介质 Download PDF

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WO2024051013A1
WO2024051013A1 PCT/CN2022/137709 CN2022137709W WO2024051013A1 WO 2024051013 A1 WO2024051013 A1 WO 2024051013A1 CN 2022137709 W CN2022137709 W CN 2022137709W WO 2024051013 A1 WO2024051013 A1 WO 2024051013A1
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tissue engineering
printing
engineering scaffold
gradient
model
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PCT/CN2022/137709
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English (en)
French (fr)
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阮长顺
屈华伟
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深圳先进技术研究院
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Publication of WO2024051013A1 publication Critical patent/WO2024051013A1/zh

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/205—Means for applying layers
    • B29C64/209—Heads; Nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/20—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B29C64/245—Platforms or substrates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C64/00—Additive manufacturing, i.e. manufacturing of three-dimensional [3D] objects by additive deposition, additive agglomeration or additive layering, e.g. by 3D printing, stereolithography or selective laser sintering
    • B29C64/30—Auxiliary operations or equipment
    • B29C64/386—Data acquisition or data processing for additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y30/00—Apparatus for additive manufacturing; Details thereof or accessories therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y50/00—Data acquisition or data processing for additive manufacturing

Definitions

  • the invention relates to the technical field of biomedical engineering, and in particular to a printing method, printing system, terminal and storage medium of a tissue engineering scaffold.
  • Traditional extrusion 3D printing usually uses commercial automated slicing tools (such as Cura, Simplify3D) to automatically fill the target model with fibers.
  • the conventional filling pattern is parallel arrangement of fibers within layers and 90° angle between fibers.
  • the printing path and printing parameters such as print head movement speed, extrusion air pressure, barrel heating temperature, extrusion head height, etc.
  • the manufacturing code is then called through the printer's control software and extrusion 3D printing is performed.
  • the printing route determines the fiber distribution of the 3D printed sample, which in turn affects the pore structure of the sample.
  • traditional extrusion 3D printing allows users to fine-tune parameters related to automatic slicing, such as the spacing between 2D curves and the height between 3D fiber layers, it is fundamentally difficult to change the default settings of its fiber filling pattern.
  • the diameter of interlayer fibers can be adjusted to achieve an axial gradient or the spacing of fibers within a layer can be adjusted to obtain linear horizontal gradient pores to a certain extent, it is difficult to achieve a radial gradient, limiting the use of extrusion 3D printing technology in gradient Applications and extensions of porous scaffolds.
  • a new strategy for continuously variable fiber diameter extrusion 3D printing allows precise control of the local porosity and pore size of extrusion 3D printing samples by adjusting the printing speed and extrusion head height of the print head throughout the printing path.
  • users are restricted from customizing printing parameters, which severely limits the development and promotion of continuously variable fiber diameter extrusion 3D printing technology. Therefore, how to build a bridge between the parametric design of continuously variable fiber diameter models and extrusion 3D printing manufacturing based on extrusion 3D printing technology is a key task that needs to be completed.
  • One of the purposes of this application is to provide a printing method for tissue engineering scaffolds, which includes the following steps:
  • tissue engineering scaffold model that meets gradient expectations, construct a specific manufacturing code that matches the designed tissue engineering scaffold model;
  • the printing of the tissue engineering scaffold is completed.
  • the step of obtaining a tissue engineering scaffold model that meets gradient expectations specifically includes the following steps:
  • the printing parameters are adjusted to obtain a tissue engineering scaffold model that meets the gradient expectations.
  • the printing parameters include printing path, printing speed and fiber diameter.
  • the step of constructing the functional relationship between printing speed and fiber diameter specifically includes the following steps:
  • v represents the printing speed (mm/s)
  • Q represents the flow rate of ⁇ -TCP/PCL ink extrusion (mm 3 /s)
  • S represents the cross-sectional area of ⁇ -TCP/PCL fiber (mm 2 );
  • v represents the printing speed (mm/s)
  • Q represents the flow rate of ⁇ -TCP/PCL ink extrusion (mm 3 /s)
  • d represents the approximate diameter of ⁇ -TCP/PCL fiber (mm).
  • the step of constructing a variable fiber diameter bionic gradient scaffold model based on the required target gradient data specifically includes the following steps:
  • variable fiber diameter bionic gradient scaffold model based on three-dimensional design software is constructed, including but not limited to Rhino and Grasshopper.
  • the step of constructing a specific manufacturing code that matches the designed tissue engineering scaffold model based on the tissue engineering scaffold model that meets gradient expectations specifically includes the following steps:
  • the printing speed corresponding to the diameter of the fiber at each place in the tissue engineering scaffold model that meets the gradient expectations is deduced
  • a specific manufacturing code matching the designed tissue engineering scaffold model is constructed.
  • the step of completing the preparation of the tissue engineering scaffold according to the specific manufacturing code specifically includes the following steps:
  • the control program of the extrusion 3D printer is used to call the rewritten specific manufacturing code to control the three-dimensional coordinate printer to complete the printing of the tissue engineering scaffold.
  • the initialization process includes zeroing of the XYZ three-dimensional coordinate motion system, preheating of the printing barrel, and setting the extrusion pressure.
  • the second purpose of this application is to provide a printing system for tissue engineering scaffolds, including:
  • the scaffold model acquisition unit acquires a tissue engineering scaffold model that meets gradient expectations
  • a specific manufacturing code generation unit based on the tissue engineering scaffold model that meets gradient expectations, constructs a specific manufacturing code that matches the designed tissue engineering scaffold model;
  • the printing unit completes printing of the tissue engineering scaffold according to the specific manufacturing code.
  • the third object of this application is to provide a terminal, which includes a processor and a memory coupled to the processor, wherein,
  • the memory stores program instructions for implementing the printing method of any one of the tissue engineering scaffolds
  • the processor is configured to execute the program instructions stored in the memory to control the printing of tissue engineering scaffolds.
  • the fourth object of this application is to provide a storage medium that stores program instructions executable by a processor, and the program instructions are used to execute any of the printing methods of tissue engineering scaffolds.
  • this application provides a printing method, printing system, terminal and storage medium for tissue engineering scaffolds.
  • the printing method for tissue engineering scaffolds provided in the above embodiments of this application, according to the variable fiber diameter bionic gradient scaffold model, adjust the printing parameters to obtain a tissue engineering scaffold model that meets the gradient expectations, and construct a specific manufacturing code that matches the designed tissue engineering scaffold model based on the tissue engineering scaffold model that meets the gradient expectations, and can be manufactured according to different printers
  • the code writing rules complete the upgrade and transformation of the traditional extrusion 3D printer, so that it can be used to prepare continuously variable fiber diameter scaffolds, reducing production and manufacturing costs.
  • Figure 1 is a step flow chart of a method for preparing a tissue engineering scaffold provided by an embodiment of the present application.
  • Figure 2 is a flow chart of steps for obtaining a tissue engineering scaffold model that meets gradient expectations provided by an embodiment of the present application.
  • Figure 3 is a flow chart of steps for constructing a specific manufacturing code that matches the designed tissue engineering scaffold model provided by the embodiment of the present application.
  • Figure 4 is a schematic structural diagram of a printing system for tissue engineering scaffolds provided by an embodiment of the present application.
  • a method for printing a tissue engineering scaffold including the following steps S10 to S30. Each step will be described in detail below.
  • Step S10 Obtain a tissue engineering scaffold model that meets gradient expectations.
  • FIG 2 is a flow chart of steps for obtaining a tissue engineering scaffold model that meets gradient expectations provided in this embodiment, specifically including the following steps S11 ⁇ S13, each step is explained in detail below.
  • Step S11 Construct a functional relationship between printing speed and fiber diameter.
  • the functional relationship between printing speed and fiber diameter is constructed, which specifically includes the following steps S111 ⁇ S112.
  • Step S111 Based on the law of conservation of mass, obtain the functional relationship between printing speed and fiber cross-sectional area:
  • v represents the printing speed (mm/s)
  • Q represents the flow rate of ⁇ -TCP/PCL ink extrusion (mm 3 /s)
  • S represents the cross-sectional area of ⁇ -TCP/PCL fiber (mm 2 );
  • Step S112 Area formula based on circle , obtain the functional relationship function(v, d) between printing speed and fiber diameter:
  • v represents the printing speed (mm/s)
  • Q represents the flow rate of ⁇ -TCP/PCL ink extrusion (mm 3 /s)
  • d represents the approximate diameter of ⁇ -TCP/PCL fiber (mm).
  • Step S12 Construct a variable fiber diameter bionic gradient scaffold model based on the required target gradient data.
  • the step of constructing a variable fiber diameter bionic gradient scaffold model based on the required target gradient data specifically includes the following steps:
  • variable fiber diameter bionic gradient scaffold model based on three-dimensional design software is constructed, including but not limited to Rhino and Grasshopper.
  • Step S13 According to the variable fiber diameter bionic gradient scaffold model, adjust printing parameters to obtain a tissue engineering scaffold model that meets gradient expectations.
  • the printing parameters include printing path, printing speed and fiber diameter.
  • the user can adjust the fiber stacking pattern by adjusting the printing parameters to obtain a tissue engineering scaffold model that meets the gradient expectations.
  • This breaks through the restriction of the traditional extrusion 3D printing model that the diameter of the filling fibers is the same everywhere, and provides a good solution for the extrusion model.
  • the preparation of controllable gradient pore scaffolds through 3D printing provides technical support.
  • Step S120 Based on the tissue engineering scaffold model that meets gradient expectations, construct a specific manufacturing code that matches the designed tissue engineering scaffold model.
  • the step of constructing a specific manufacturing code that matches the designed tissue engineering scaffold model based on the tissue engineering scaffold model that meets gradient expectations specifically includes the following steps S121 ⁇ S123.
  • Step S121 According to the tissue engineering scaffold model that meets the gradient expectations, deduct the printing speed corresponding to the fiber diameter at each place in the tissue engineering scaffold model that meets the gradient expectations.
  • Step S122 Determine a matching extrusion head height by combining the position of the fiber and the diameter of the fiber.
  • Step S123 Construct a specific manufacturing code that matches the designed tissue engineering scaffold model according to the writing rules of the extrusion 3D printer manufacturing code of the programming tool.
  • the extrusion 3D printer includes but is not limited to Regenovo Bio-Architect® WS.
  • the extrusion 3D printing includes but is not limited to normal temperature extrusion 3D printing and low-temperature freezing extrusion 3D printing.
  • the printing ink of the extrusion 3D printer includes but is not limited to ⁇ -TCP/PCL.
  • the manufacturing code writing rules of the extrusion 3D printer are written to match the manufacturing code of the design model using programming tools, including but not limited to GHPython.
  • the printing parameters are adjusted to obtain a tissue engineering scaffold model that meets the gradient expectations to obtain a manufacturing code that matches the design model.
  • Step S30 Complete the printing of the tissue engineering scaffold according to the specific manufacturing code.
  • the step of completing the preparation of the tissue engineering scaffold according to the specific manufacturing code specifically includes the following steps: using the control program of the extrusion 3D printer to call the rewritten specific manufacturing code , controlling the three-coordinate printer to complete the printing of tissue engineering scaffolds.
  • Step S40 Install the extrusion head and prepare printing ink.
  • Step S50 Complete the initialization process of the three-dimensional coordinate printer based on the control program of the extrusion 3D printer.
  • the initialization process includes zeroing the XYZ three-dimensional coordinate motion system, preheating the printing barrel, and setting the extrusion pressure.
  • the printing method of the tissue engineering scaffold provided by the above embodiments of the present application is based on the variable fiber diameter bionic gradient scaffold model, adjusting the printing parameters to obtain a tissue engineering scaffold model that meets the gradient expectations, and based on the tissue engineering scaffold model that meets the gradient expectations , construct a specific manufacturing code that matches the designed tissue engineering scaffold model, and can complete the upgrade and transformation of the traditional extrusion 3D printer according to the writing rules of different printer manufacturing codes, so that it can be used to prepare continuously variable fiber diameter scaffolds , reducing production and manufacturing costs.
  • the tissue engineering scaffold obtained through the above method can be used in bone tissue engineering, meniscal tissue engineering, vascular tissue engineering and other fields that require gradient pores, and is widely used.
  • FIG 4 is a schematic structural diagram of a tissue engineering scaffold printing system according to an embodiment of the present application, including: a scaffold model acquisition unit 110, used to obtain a tissue engineering scaffold model that meets gradient expectations; a specific manufacturing code generation unit 120, for constructing a specific manufacturing code that matches the designed tissue engineering scaffold model based on the tissue engineering scaffold model that meets gradient expectations; the printing unit 130, for completing the tissue engineering scaffold based on the specific manufacturing code of printing.
  • An embodiment of the present application provides a printing system for a tissue engineering scaffold.
  • the printing parameters are adjusted to obtain a tissue engineering scaffold model that meets the gradient expectations, and based on the tissue engineering scaffold that meets the gradient expectations, Model, construct a specific manufacturing code that matches the designed tissue engineering scaffold model, and complete the upgrade and transformation of the traditional extrusion 3D printer according to the writing rules of different printer manufacturing codes, so that it can be used to prepare continuously variable fiber diameters bracket, reducing production and manufacturing costs.
  • the present application also provides a terminal, which includes a processor and a memory coupled to the processor, wherein the memory stores program instructions for implementing any of the printing methods of tissue engineering scaffolds. ;
  • the processor is used to execute the program instructions stored in the memory to control the printing of the tissue engineering scaffold.
  • This application also provides a storage medium that stores program files that can implement the printing method of the tissue engineering scaffold provided by any one of the above.
  • the technical advantages of the embodiments of the present invention are at least that: according to the variable fiber diameter bionic gradient scaffold model, the printing parameters are adjusted to obtain a tissue engineering scaffold model that meets the gradient expectations, and based on the tissue engineering scaffold model that meets the gradient expectations, a tissue engineering scaffold model that meets the gradient expectations is constructed. Design a specific manufacturing code that matches the tissue engineering scaffold model, and complete the upgrade of the traditional extrusion 3D printer according to the writing rules of different printer manufacturing codes, so that it can be used to prepare continuously variable fiber diameter scaffolds, reducing production manufacturing cost.
  • this invention introduces a new extrusion 3D printing strategy of continuously controllable fiber diameter by changing the printing speed and the height of the extrusion head. It obtains a gradient pore structure by precisely controlling the changes in the diameter of the filling fibers everywhere. This requires that the fibers distributed throughout the entire model should have corresponding printing speeds and extrusion head heights to ensure printing speed and extrusion. The head height is consistent with the fiber diameter.
  • the gradient pores of the scaffold can be adjusted with one click and the manufacturing code that matches the design model can be obtained , building a bridge between variable fiber diameter design and extrusion 3D printers based on the software Rhino and Grasshopper.
  • the invention has been experimentally verified and proved feasible.

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Abstract

一种组织工程支架的打印方法，根据变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，并且根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码，而且可根据不同打印机制造代码的书写规则，完成传统挤出式3D打印机的升级改造，使其可以用于制备连续变纤维直径支架，降低了生产制造成本。另外，还提供了一种组织工程支架的打印系统、终端及存储介质。

Description

组织工程支架的打印方法、打印系统、终端及存储介质 技术领域
本发明涉及生物医学工程技术领域，特别涉及一种组织工程支架的打印方法、打印系统、终端及存储介质。
 背景技术
传统挤出式3D打印通常使用商业化的自动化切片工具（如Cura、Simplify3D）对目标模型进行自动化纤维填充，其常规填充图案为层内纤维平行排布、层间纤维90°夹角。然后基于打印机制造代码的书写规则，将自动化切片获得的打印路径和打印参数（如打印头移动速度、挤出气压、料筒加热温度、挤出头高度等）转换为挤出式3D打印机可以识别的制造代码，进而通过打印机的控制软件对其进行调用并执行挤出式3D打印。
在挤出式3D打印过程中，打印路线（即2D填充曲线）决定了3D打印样品的纤维分布情况，进而影响样品的孔隙结构。传统挤出式3D打印虽然允许用户对自动切片的相关参数进行微调，如2D曲线之间的间距、3D纤维层间的高度等参数，但是从根本上难以更改其纤维填充图案的默认设定。此外，尽管可以调整层间纤维的直径来实现轴向梯度或者调整层内纤维的间距在一定程度上获得线性的水平梯度孔隙，但是其难以实现径向梯度，限制挤出式3D打印技术在梯度孔隙支架的应用和扩展。
连续变纤维直径挤出式3D打印新策略通过调整打印头在打印路径各处的打印速度和挤出头高度来精确控制挤出式3D打印样品的局部孔隙率和孔径。但是由于传统挤出式3D打印的自动化切片封装，限制用户对打印参数的自定义设置，这严重限制了连续变纤维直径挤出式3D打印技术的发展和技术推广。因此，如何基于挤出式3D打印技术搭建连续变纤维直径模型参数化设计和挤出式3D打印制造的桥梁是一项亟待完成的关键工作。
目前现有技术缺乏搭建连续变纤维直径模型参数化设计和挤出式3D打印制造的桥梁。尽管有文献（Diaz-Gomez L, Kontoyiannis P D, Melchiorri A J, et al. Three-dimensional printing of tissue engineering scaffolds with horizontal pore and composition gradients[J]. Tissue Engineering Part C-Methods, 2019, 25(7): 411-420）基于传统挤出式3D打印技术，通过在径向不同区域设置不同的纤维直径和间距来实现径向梯度孔隙，但是该方法难以制备高精度、连续、可控的梯度孔隙支架。
 技术问题
有鉴如此，有必要针对现有技术存在的难以制备高精度、连续、可控的梯度孔隙支架的问题，提供一种可具有加工连续变纤维直径样品的能力的组织工程支架的打印方法。
 技术解决方案
为实现上述目的，本申请采用下述技术方案：
本申请的目的之一提供了一种组织工程支架的打印方法，包括下述步骤：
获取符合梯度预期的组织工程支架模型；
根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码；
根据所述特异性制造代码，完成组织工程支架的打印。
在其中一些实施例中，在获取符合梯度预期的组织工程支架模型的步骤中，具体包括下述步骤：
构建打印速度与纤维直径的函数关系；
根据所需目标梯度数据，构建变纤维直径仿生梯度支架模型；
根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，所述打印参数包括打印路径、打印速度和纤维直径。
在其中一些实施例中，在构建打印速度与纤维直径的函数关系的步骤中，具体包括下述步骤：
基于质量守恒定律，获得打印速度与纤维截面面积的函数关系：
式中： v表示打印速度（mm/s）、 Q表示β-TCP/PCL墨水挤出的流量（mm 3/s）、 S表示β-TCP/PCL纤维的截面面积（mm 2）；
基于圆的面积公式 ，获得打印速度与纤维直径的函数关系function( v, d)：
式中： v表示打印速度（mm/s）、 Q表示β-TCP/PCL墨水挤出的流量（mm 3/s）、d表示β-TCP/PCL纤维的近似直径（mm）。
在其中一些实施例中，在根据所需目标梯度数据，构建变纤维直径仿生梯度支架模型的步骤中，具体包括下述步骤：
根据所需目标梯度数据构建基于三维设计软件的变纤维直径仿生梯度支架模型，所述三维设计软件包括但不限于Rhino、Grasshopper。
在其中一些实施例中，在根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码的步骤中，具体包括下述步骤：
根据所述符合梯度预期的组织工程支架模型，基于纤维在所述符合梯度预期的组织工程支架模型各处的直径反推出与其相对应的打印速度；
结合所述纤维的位置和所述纤维的直径确定相匹配的挤出头高度；
根据编程工具基于挤出式3D打印机制造代码的书写规则，构建与所设计组织工程支架模型相匹配的特异性制造代码。
在其中一些实施例中，在根据所述特异性制造代码，完成组织工程支架的制备的步骤中，具体包括下述步骤：
使用挤出式3D打印机的控制程序调用重写的特异性制造代码，控制三坐标打印机完成组织工程支架的打印。
在其中一些实施例中，在获取符合梯度预期的组织工程支架模型的步骤之前，还包括下述步骤：
安装挤出头工作及准备打印墨水；
基于挤出式3D打印机的控制程序完成对三坐标打印机进行初始化处理，所述初始化处理包括XYZ三坐标运动系统归零、打印料筒的预加热、设置挤出压力。
本申请目的之二提供了一种组织工程支架的打印系统，包括：
支架模型获取单元，获取符合梯度预期的组织工程支架模型；
特异性制造代码生成单元，根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码；
打印单元，根据所述特异性制造代码，完成组织工程支架的打印。
本申请目的之三提供了一种终端，所述终端包括处理器、与所述处理器耦接的存储器，其中，
所述存储器存储有用于实现任一项所述的组织工程支架的打印方法的程序指令；
所述处理器用于执行所述存储器存储的所述程序指令以控制组织工程支架的打印。
本申请目的之四提供了一种存储介质，存储有处理器可运行的程序指令，所述程序指令用于执行任一项所述组织工程支架的打印方法。
 有益效果
采用上述技术方案，本申请具有以下技术效果：
相对于现有技术，本申请提供了一种组织工程支架的打印方法、打印系统、终端及存储介质，本申请上述实施例提供的组织工程支架的打印方法，根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，并且根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码，而且可根据不同打印机制造代码的书写规则，完成传统挤出式3D打印机的升级改造，使其可以用于制备连续变纤维直径支架，降低了生产制造成本。
 附图说明
此处所说明的附图用来提供对本发明的进一步理解，构成本申请的一部分，本发明的示意性实施例及其说明用于解释本发明，并不构成对本发明的不当限定。在附图中：
图1为本申请实施例提供的组织工程支架的制备方法的步骤流程图。
图2为本申请实施例提供的在获取符合梯度预期的组织工程支架模型的步骤流程图。
图3为本申请实施例提供的构建与所设计组织工程支架模型相匹配的特异性制造代码的步骤流程图。
图4为本申请实施例提供的组织工程支架的打印系统的结构示意图。
 本发明的实施方式
为了使本技术领域的人员更好地理解本发明方案，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分的实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都应当属于本发明保护的范围。
需要说明的是，本发明的说明书和权利要求书及上述附图中的术语“第一”、“第二”等是用于区别类似的对象，而不必用于描述特定的顺序或先后次序。应该理解这样使用的数据在适当情况下可以互换，以便这里描述的本发明的实施例能够以除了在这里图示或描述的那些以外的顺序实施。此外，术语“包括”和“具有”以及他们的任何变形，意图在于覆盖不排他的包含，例如，包含了一系列步骤或单元的过程、方法、系统、产品或设备不必限于清楚地列出的那些步骤或单元，而是可包括没有清楚地列出的或对于这些过程、方法、产品或设备固有的其它步骤或单元。
请参阅图1，根据本发明一实施例，提供了一种组织工程支架的打印方法，包括下述步骤S10~S30，以下针对各个步骤进行详细说明。
步骤S10：获取符合梯度预期的组织工程支架模型。
请参阅图2，为本实施例提供的在获取符合梯度预期的组织工程支架模型的步骤流程图，具体包括下述步骤S11~ S13，以下针对各个步骤进行详细说明。
步骤S11：构建打印速度与纤维直径的函数关系。
作为本申请的一种改进，，构建打印速度与纤维直径的函数关系，具体包括下述步骤S111~S112。
步骤S111：基于质量守恒定律，获得打印速度与纤维截面面积的函数关系：
式中： v表示打印速度（mm/s）、 Q表示β-TCP/PCL墨水挤出的流量（mm 3/s）、 S表示β-TCP/PCL纤维的截面面积（mm 2）；
步骤S112：基于圆的面积公式 ，获得打印速度与纤维直径的函数关系function(v, d)：
式中： v表示打印速度（mm/s）、 Q表示β-TCP/PCL墨水挤出的流量（mm 3/s）、 d表示β-TCP/PCL纤维的近似直径（mm）。
通过上述S111~ S112构建打印速度与纤维直径的函数关系。
步骤S12：根据所需目标梯度数据，构建变纤维直径仿生梯度支架模型。
作为本申请的一种改进，在根据所需目标梯度数据，构建变纤维直径仿生梯度支架模型的步骤中，具体包括下述步骤：
根据所需目标梯度数据构建基于三维设计软件的变纤维直径仿生梯度支架模型，所述三维设计软件包括但不限于Rhino、Grasshopper。
步骤S13：根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，所述打印参数包括打印路径、打印速度和纤维直径。
可以理解，用户根据支架所需性能，通过调整打印参数调整纤维堆积图案来获得符合梯度预期的组织工程支架模型，突破了传统挤出式3D打印模型各处填充纤维直径均相同的制约，为挤出式3D打印制备可控梯度孔隙支架提供了技术支撑。
步骤S120：根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码。
请参参阅图3，在根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码的步骤中，具体包括下述步骤S121~ S123。
步骤S121：根据所述符合梯度预期的组织工程支架模型，基于纤维在所述符合梯度预期的组织工程支架模型各处的直径反推出与其相对应的打印速度。
步骤S122：结合所述纤维的位置和所述纤维的直径确定相匹配的挤出头高度。
步骤S123：根据编程工具基于挤出式3D打印机制造代码的书写规则，构建与所设计组织工程支架模型相匹配的特异性制造代码。
作为本申请的一种改进，所述挤出式3D打印机包括但不限于捷诺飞Regenovo Bio-Architect® WS。
作为本申请的另一种改进，所述挤出式3D打印，包括但不限于常温挤出式3D打印，低温冷冻挤出式3D打印。
作为本申请的另一种改进，所述挤出式3D打印机的打印墨水，包括但不限于β-TCP/PCL。
作为本申请的另一种改进，所述挤出式3D打印机的制造代码书写规则编写设计模型相匹配的制造代码所使用的编程工具，包括但不限于GHPython。
可以理解，根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型以获得与设计模型相匹配的制造代码。
步骤S30：根据所述特异性制造代码，完成组织工程支架的打印。
作为本申请的一种改进，在根据所述特异性制造代码，完成组织工程支架的制备的步骤中，具体包括下述步骤：使用挤出式3D打印机的控制程序调用重写的特异性制造代码，控制三坐标打印机完成组织工程支架的打印。
作为本申请的另一种改进，在获取符合梯度预期的组织工程支架模型的步骤之前，还包括下述步骤：
步骤S40：安装挤出头工作及准备打印墨水。
步骤S50：基于挤出式3D打印机的控制程序完成对三坐标打印机进行初始化处理，所述初始化处理包括XYZ三坐标运动系统归零、打印料筒的预加热、设置挤出压力。
本申请上述实施例提供的组织工程支架的打印方法，根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，并且根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码，而且可根据不同打印机制造代码的书写规则，完成传统挤出式3D打印机的升级改造，使其可以用于制备连续变纤维直径支架，降低了生产制造成本。通过上述方法获取的组织工程支架可应用于骨组织工程、半月板组织工程、血管组织工程等对梯度孔隙有需要的领域，应用广泛。
请参阅图4，根据本申请实施例提供的一种组织工程支架的打印系统的结构示意图，包括：支架模型获取单元110，用于获取符合梯度预期的组织工程支架模型；特异性制造代码生成单元120，用于根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码；打印单元130，用于根据所述特异性制造代码，完成组织工程支架的打印。
本实施例提供的组织工程支架的打印系统，其详细的实现方案在上述实施例中已有详细说明，这里不再赘述。
本申请实施例提供的一种组织工程支架的打印系统，根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，并且根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码，而且可根据不同打印机制造代码的书写规则，完成传统挤出式3D打印机的升级改造，使其可以用于制备连续变纤维直径支架，降低了生产制造成本。
本申请还提供了一种终端，所述终端包括处理器、与所述处理器耦接的存储器，其中，所述存储器存储有用于实现任一项所述的组织工程支架的打印方法的程序指令；所述处理器用于执行所述存储器存储的所述程序指令以控制组织工程支架的打印。
本申请还提供了一种存储介质，存储介质存储有能够实现上述任意一项提供的组织工程支架的打印方法的程序文件。
本发明实施例的技术优点至少在于：根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，并且根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码，而且可根据不同打印机制造代码的书写规则，完成传统挤出式3D打印机的升级改造，使其可以用于制备连续变纤维直径支架，降低了生产制造成本。
以下结合具体实施例对上述技术方案进行详细说明。具体实施案例如下：
实施例1：
A.      本发明在传统挤出式3D打印技术的基础上引入变化打印速度和变化挤出头高度的连续可控纤维直径的挤出式3D打印新策略。其通过精确控制填充纤维在各处直径的变化来获得梯度孔隙结构，这就要求在整个模型各处分布的纤维均应具有与其对应的打印速度和挤出头高度，才能保证打印速度和挤出头高度与纤维直径保持一致。
B.      选择β-TCP（Sigma-Aldrich，美国）和分子量为14000的PCL（Aldrich，美国）以25%（w/w）的重量比混合制备β-TCP/PCL墨水材料。首先，将它们放在72℃的加热箱中1小时，然后在室温下用药勺搅拌均匀，重复这个过程3次。
C.      选择中国捷诺飞公司生产的Regenovo Bio-Architect® WS挤出式3D打印机作为本研究的硬件平台，该打印机可以实现XYZ三坐标轴联动，满足本发明对打印速度和挤出头高度的运动控制需求，并可获得该打印机制造代码的书写规则。另外，与该款挤出式3D打印机相配套的控制软件为Bio-Architect.exe。
D.      确定打印参数为：挤出气压（400 kPa）、挤出头尺寸（400μm）、加热温度（72 ℃）、墨水材料等打印参数。
E. 为了实现本发明所提出的可控梯度组织工程支架的参数化设计和变纤维直径挤出式3D打印制备，并且可以一键式调整支架的梯度孔隙并获得与设计模型相匹配的制造代码，搭建了基于软件Rhino和Grasshopper的变纤维直径设计和挤出式3D打印机的桥梁。
F. 基于捷诺飞公司的Regenovo Bio-Architect® WS挤出式3D打印机制造代码的书写规则，借助Grasshopper的编程工具GHPython将打印路径和与各处路径相匹配的打印速度、挤出头高度转换为打印设备可识别的运动控制指令。最后，通过挤出式3D打印机、预准备的β-TCP/PCL墨水和重写的制造代码完成变纤维直径挤出式3D打印梯度孔隙组织工程支架的制备。
本发明经过实验验证，证明可行。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (10)

  1. 一种组织工程支架的打印方法，其特征在于，包括下述步骤：
    获取符合梯度预期的组织工程支架模型；
    根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码；
    根据所述特异性制造代码，完成组织工程支架的打印。
  2. 根据权利要求1所述的组织工程支架的打印方法，其特征在于，在获取符合梯度预期的组织工程支架模型的步骤中，具体包括下述步骤：
    构建打印速度与纤维直径的函数关系；
    根据所需目标梯度数据，构建变纤维直径仿生梯度支架模型；
    根据所述变纤维直径仿生梯度支架模型，调整打印参数获得符合梯度预期的组织工程支架模型，所述打印参数包括打印路径、打印速度和纤维直径。
  3. 根据权利要求2所述的组织工程支架的打印方法，其特征在于，在构建打印速度与纤维直径的函数关系的步骤中，具体包括下述步骤：
    基于质量守恒定律，获得打印速度与纤维截面面积的函数关系：
    式中： v表示打印速度（mm/s）、 Q表示β-TCP/PCL墨水挤出的流量（mm 3/s）、 S表示β-TCP/PCL纤维的截面面积（mm 2）；
    基于圆的面积公式 ，获得打印速度与纤维直径的函数关系function( v, d)：
    式中： v表示打印速度mm/s、 Q表示β-TCP/PCL墨水挤出的流量mm 3/s、 d表示β-TCP/PCL纤维的近似直径mm。
  4. 根据权利要求2所述的组织工程支架的打印方法，其特征在于，在根据所需目标梯度数据，构建变纤维直径仿生梯度支架模型的步骤中，具体包括下述步骤：
    根据所需目标梯度数据构建基于三维设计软件的变纤维直径仿生梯度支架模型，所述三维设计软件包括但不限于Rhino、Grasshopper。
  5. 根据权利要求1所述的组织工程支架的打印方法，其特征在于，在根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码的步骤中，具体包括下述步骤：
    根据所述符合梯度预期的组织工程支架模型，基于纤维在所述符合梯度预期的组织工程支架模型各处的直径反推出与其相对应的打印速度；
    结合所述纤维的位置和所述纤维的直径确定相匹配的挤出头高度；
    根据编程工具基于挤出式3D打印机制造代码的书写规则，构建与所设计组织工程支架模型相匹配的特异性制造代码。
  6. 根据权利要求1所述的组织工程支架的打印方法，其特征在于，在根据所述特异性制造代码，完成组织工程支架的制备的步骤中，具体包括下述步骤：
    使用挤出式3D打印机的控制程序调用重写的特异性制造代码，控制三坐标打印机完成组织工程支架的打印。
  7. 根据权利要求1所述的组织工程支架的打印方法，其特征在于，在获取符合梯度预期的组织工程支架模型的步骤之前，还包括下述步骤：
    安装挤出头工作及准备打印墨水；
    基于挤出式3D打印机的控制程序完成对三坐标打印机进行初始化处理，所述初始化处理包括XYZ三坐标运动系统归零、打印料筒的预加热、设置挤出压力。
  8. 一种组织工程支架的打印系统，其特征在于，包括：
    支架模型获取单元，获取符合梯度预期的组织工程支架模型；
    特异性制造代码生成单元，根据所述符合梯度预期的组织工程支架模型，构建与所设计组织工程支架模型相匹配的特异性制造代码；
    打印单元，根据所述特异性制造代码，完成组织工程支架的打印。
  9. 一种终端，其特征在于，所述终端包括处理器、与所述处理器耦接的存储器，其中，
    所述存储器存储有用于实现权利要求1-6任一项所述的组织工程支架的打印方法的程序指令；
    所述处理器用于执行所述存储器存储的所述程序指令以控制组织工程支架的打印。
  10. 一种存储介质，其特征在于，存储有处理器可运行的程序指令，所述程序指令用于执行权利要求1-6任一项所述组织工程支架的打印方法。
PCT/CN2022/137709 2022-09-06 2022-12-08 组织工程支架的打印方法、打印系统、终端及存储介质 WO2024051013A1 (zh)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105477682A (zh) * 2016-01-20 2016-04-13 北京大学第三医院 一种组织工程半月板支架及制备方法
CN106178124A (zh) * 2016-07-13 2016-12-07 华南理工大学 一种可降解高分子网络/磷酸钙骨水泥复合骨修复材料及其制备方法与应用
CN106999635A (zh) * 2014-12-11 2017-08-01 苏黎世联邦理工学院 软骨修复用移植物支架及其制造方法
CN110385851A (zh) * 2018-04-19 2019-10-29 波音公司 液滴拉伸和挤压打印方法
CN111110404A (zh) * 2020-01-10 2020-05-08 苏州诺普再生医学有限公司 一种3d打印的多结构骨复合支架
CN114642764A (zh) * 2020-12-18 2022-06-21 中国科学院深圳先进技术研究院 骨组织工程分形状支架构建方法
WO2022126594A1 (zh) * 2020-12-18 2022-06-23 中国科学院深圳先进技术研究院 骨组织工程分形状支架构建方法

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9604407B2 (en) * 2013-12-03 2017-03-28 Xerox Corporation 3D printing techniques for creating tissue engineering scaffolds
KR20150097087A (ko) * 2014-02-18 2015-08-26 한국기계연구원 복합 스캐폴드 제조 방법 및 이를 이용하여 제조된 복합 스캐폴드
CN105013011B (zh) * 2015-07-22 2018-01-05 青岛尤尼科技有限公司 一种组织工程半月板支架的3d生物打印制备方法
KR102003256B1 (ko) * 2017-04-21 2019-07-25 동국대학교 산학협력단 3d 프린터의 가변 압출 방법, 3d 모델 출력 방법 및 이를 위한 3d 모델 출력 시스템
CN109228325A (zh) * 2018-08-31 2019-01-18 上海大学 通过添加标志位信息制备三维多材料多尺度生物支架的系统和方法
CN110001067B (zh) * 2019-03-27 2022-01-18 北京机科国创轻量化科学研究院有限公司 一种连续纤维增强复合材料3d打印路径规划方法
GB2584702B (en) * 2019-06-12 2022-05-04 Ai Build Ltd Adjusting three-dimensional print parameters
CN112979303B (zh) * 2021-02-09 2022-01-04 浙江大学 一种降解速度可调的骨组织梯度支架及其基于3d打印的成型方法
CN113458387B (zh) * 2021-07-02 2023-07-18 中国科学院宁波材料技术与工程研究所 一种3d打印梯度陶瓷金属材料以及制备方法
CN114654719B (zh) * 2022-02-25 2023-03-24 北京航空航天大学 一种活塞式直写打印中沉积细丝宽度与高度的预测方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106999635A (zh) * 2014-12-11 2017-08-01 苏黎世联邦理工学院 软骨修复用移植物支架及其制造方法
CN105477682A (zh) * 2016-01-20 2016-04-13 北京大学第三医院 一种组织工程半月板支架及制备方法
CN106178124A (zh) * 2016-07-13 2016-12-07 华南理工大学 一种可降解高分子网络/磷酸钙骨水泥复合骨修复材料及其制备方法与应用
CN110385851A (zh) * 2018-04-19 2019-10-29 波音公司 液滴拉伸和挤压打印方法
CN111110404A (zh) * 2020-01-10 2020-05-08 苏州诺普再生医学有限公司 一种3d打印的多结构骨复合支架
CN114642764A (zh) * 2020-12-18 2022-06-21 中国科学院深圳先进技术研究院 骨组织工程分形状支架构建方法
WO2022126594A1 (zh) * 2020-12-18 2022-06-23 中国科学院深圳先进技术研究院 骨组织工程分形状支架构建方法

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