WO2023179418A1 - 具有取向结构的肩袖补片及其制备方法 - Google Patents

具有取向结构的肩袖补片及其制备方法 Download PDF

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WO2023179418A1
WO2023179418A1 PCT/CN2023/081558 CN2023081558W WO2023179418A1 WO 2023179418 A1 WO2023179418 A1 WO 2023179418A1 CN 2023081558 W CN2023081558 W CN 2023081558W WO 2023179418 A1 WO2023179418 A1 WO 2023179418A1
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rotator cuff
oriented structure
patch
preparing
cuff patch
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PCT/CN2023/081558
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English (en)
French (fr)
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朱同贺
杜娟
陈思浩
包一鸣
邢晨晨
陈晨
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上海工程技术大学
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Publication of WO2023179418A1 publication Critical patent/WO2023179418A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/08—Muscles; Tendons; Ligaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/20—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/225—Fibrin; Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A61F2240/002—Designing or making customized prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/24—Materials or treatment for tissue regeneration for joint reconstruction

Definitions

  • the invention belongs to the technical fields of tissue engineering and biomedicine, and specifically relates to a rotator cuff patch with an oriented structure and a preparation method thereof.
  • Rotator cuff tear is a common shoulder joint disease, which mainly involves damage to the tendon soft tissue and bone hard tissue of the shoulder joint due to sports. The incidence gradually increases with age. Rotator cuff tears are a common cause of shoulder joint pain, reduced mobility, and weakened function, accounting for approximately 60% of shoulder pathologies. For patients with rotator cuff injuries who fail to respond to conservative treatment or patients with large-scale rotator cuff injuries, surgical treatment is usually performed to repair the torn tendons, thereby reducing pain and rebuilding joint function.
  • the current rotator cuff patch regardless of the porcine dermal patch used clinically, is not easy to heal at the tendon-bone interface (tendon-bone interface) after rotator cuff repair; therefore, by constructing a tissue-induced patch Migrate nearby tendon stem cells and other precursor cells to the injured tendon site. Therefore, designing simulated rotator cuff tissue with excellent mechanical strength may be an effective way to solve the above related problems. Therefore, functional shoulder oil with good biocompatibility Mesh has important clinical application value in the treatment of rotator cuff injuries.
  • the purpose of the present invention is to provide a rotator cuff patch with an oriented structure and a preparation method thereof.
  • the present invention provides a method for preparing a rotator cuff patch with an oriented structure, which includes the following steps:
  • the natural source matrix material is selected from at least one type of collagen, gelatin, fibroin, chitosan, lactose and aminoglycoside.
  • the solvent is selected from at least one type of hexafluoroisopropanol, trifluoroacetic acid, ultrapure water and acetic acid aqueous solution.
  • the mass volume (w/v) concentration of the first mixed liquid and the second mixed liquid is 1-20%.
  • the osteogenic factor is selected from bone morphogenetic protein (BMP-2), basic fibroblast growth factor (FGF-2), insulin-like growth factor (IGF-2), Nell-1 , deferoxamine and more than one RGD short peptide.
  • BMP-2 bone morphogenetic protein
  • FGF-2 basic fibroblast growth factor
  • IGF-2 insulin-like growth factor
  • Nell-1 deferoxamine and more than one RGD short peptide.
  • the temperature of directional crystallization is (-200)-(-20)°C
  • the temperature during the directional crystallization process is a gradient cooling, that is, along with the directional crystallization process, according to different material types, the temperature is 1- Cool down at a rate of 50°C/h. For example, the temperature is first lowered at 5°C/h for 2 hours, then at 10°C/h until the crystallization point is reached, and the temperature is maintained for 12-24 hours.
  • the thickness of the pre-frozen sample is 0.1-10 mm.
  • steps (3) and (4) after the pouring solution solidifies, the layers are tightly bonded and are not easy to delaminate.
  • the osteogenic layer can be horizontally combined with the tendon layer or completely covered on the tendon layer to form a gradient structure from the tendon layer to the osteogenic layer.
  • step (4) on the one hand, the gradient structure is caused by the longer pre-freezing time of the crystallized frozen solid than the second mixed liquid; on the other hand, during the process of pouring the second mixed liquid on the surface of the frozen solid, the pouring temperature difference will Local dissolution and pore collapse occur, and then it is mixed with the second mixed liquid and pre-frozen to form a multi-layered pore structure, so the final sample has a gradient structure.
  • the rotator cuff patch with an oriented structure has a pore diameter of 10-200 ⁇ m and an orientation degree of 0-180°.
  • the temperature of low-temperature freeze-drying is (-80)-(-30)°C.
  • the present invention provides a rotator cuff patch with an oriented structure, which is obtained by the above preparation method.
  • the solvent forms a eutectic when it reaches the eutectic point during the freezing process.
  • the solution will undergo a glass transition and the crystal shape may also change. This process will cause the pore size of the sample to change during the freeze-drying process.
  • Controlling the freezing temperature i.e., the crystallization temperature
  • the cooling temperature and speed during the freeze-drying process have a great impact on the stability of the sample structure when the sample is freeze-dried. Therefore, the present invention prepares materials with suitable pore size and orientation by regulating the crystallization temperature and freeze-drying cooling rate in the directional crystallization technology.
  • Rotator cuff patch has been widely used in tissue engineering repair research and clinical rotator cuff repair. It has good biomechanical properties and biocompatibility, and can be used for the regenerative treatment of rotator cuff tissue injury diseases; in addition, the material of the present invention It has a wide range of sources, a simple and efficient preparation method, low price, and has good clinical application prospects.
  • Figure 1 is a SEM schematic diagram of an oriented rotator cuff patch in Example 1 of the present invention.
  • the invention provides a rotator cuff patch with an oriented structure and a preparation method thereof.

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Abstract

本发明提供了一种具有取向结构的肩袖补片及其制备方法，制备方法包括：将天然源基质材料加入溶剂中得到第一混合液，作为肩袖肌腱层一端的主要成分；将天然源基质材料和成骨因子加入溶剂中，得到第二混合液，作为肩袖成骨层一端的主要成分；将第一混合液浇筑于特定模具中，定向结晶；将第二混合液浇筑于冷冻固态物上，形成具有不同梯度结构的预冻样品；将预冻样品转移至冷冻干燥机中，梯度低温冷冻干燥即可；本发明通过调控定向结晶技术中的结晶温度和冷冻干燥降温速率，制备具有适宜孔径、孔隙率以及取向度的肩袖补片，用于临床肩袖修复；本发明的材料来源广泛，制备方法简单高效，价格低廉，具有良好的临床应用前景。

Description

具有取向结构的肩袖补片及其制备方法 技术领域
本发明属于组织工程和生物医药技术领域，具体涉及一种具有取向结构的肩袖补片及其制备方法。
背景技术
肩袖撕裂是常见的肩关节性疾病，主要涉及肩关节处肌腱软组织和骨硬组织由于运动发生的损伤，发病率随着年龄的增长而逐渐增加。肩袖撕裂是导致肩关节疼痛、活动度降低、功能减弱的常见原因，约占肩部病变的60％。对经保守治疗无效的肩袖损伤患者及肩袖大面积损伤患者，通常采取外科手术治疗修补撕裂肌腱，从而减轻疼痛，并重建关节功能。
而现阶段的肩袖补片，不论临床上使用的猪源真皮补片由于肩袖修补术后肌腱-骨交界面处(肌腱-骨界面)不易愈合；因此通过构建具有组织诱导型的补片将附近的肌腱干细胞等前体细胞等迁移到肌腱损伤局部，因此设计力学强度优良模拟肩袖组织也许是一种有效的方式来解决以上有关问题，故具有良好生物相容性的功能型肩油补片对于治疗肩袖损伤有重要的临床应用价值。
发明内容
针对现有技术中肩袖补片肌腱不够仿生，且支架孔隙率结构不足的问题，本发明的目的是提供一种具有取向结构的肩袖补片及其制备方法。
为达到上述目的，本发明的解决方案是：
作为第一方面，本发明提供了一种具有取向结构的肩袖补片的制备方法，其包括如下步骤：
(1)、将天然源基质材料加入溶剂中得到第一混合液，作为肩袖肌腱层一端的主要成分；
(2)、将天然源基质材料加入溶剂中，混合均匀后加入活性的成骨因子，得到第二混合液，作为含有成骨因子的肩袖成骨层一端的主要成分；
(3)、将第一混合液浇筑于特定316L不锈钢方形模具中，定向结晶，结晶后得到冷冻固态物；
(4)、将第二混合液浇筑于步骤(3)的冷冻固态物上，进行预冻，形成具有不同梯度结构的预冻样品；
(5)、将预冻样品转移至冷冻干燥机中，通过梯度低温冷冻干燥，得到具有取向结构的肩袖补片。
优选地，步骤(1)和步骤(2)中，天然源基质材料选自胶原、明胶、蚕丝蛋白、壳聚糖、乳糖和氨糖中的一种以上。
优选地，步骤(1)和步骤(2)中，溶剂选自六氟异丙醇、三氟乙酸、超纯水和乙酸水溶液中的一种以上。
优选地，步骤(1)和步骤(2)中，第一混合液和第二混合液的质量体积(w/v)浓度均为1-20％。
优选地，步骤(2)中，成骨因子选自骨形态发生蛋白(BMP-2)、碱性成纤维细胞生长因子(FGF-2)、胰岛素样生长因子(IGF-2)、Nell-1、去铁胺和RGD短肽中的一种以上。
优选地，步骤(3)中，定向结晶的温度为(-200)-(-20)℃，定向结晶过程中温度为梯度降温，即随着定向结晶过程，根据不同材料类型，温度以1-50℃/h速度向下降温，如温度先以5℃/h降温2h后，再以10℃/h降温，直至达结晶点后，维持温度12-24h。
优选地，步骤(4)中，预冻样品的厚度为0.1-10mm。
步骤(3)和步骤(4)中，浇筑的溶液凝固之后，层与层间粘结紧密，不易分层。
步骤(4)中，在浇筑过程中成骨层可与肌腱层水平结合或全覆盖于肌腱层上，形成肌腱层到成骨层的梯度结构。
步骤(4)中，梯度结构一方面由结晶后的冷冻固态物预冻时间比第二混合液较长造成；另一方面，第二混合液浇筑冷冻固态物表面的过程中，由于浇筑温差会出现局部溶解和孔坍塌，再与第二混合液进行混合预冻形成多层的孔结构，因此最终形成的样品具有梯度结构。
优选地，步骤(5)中，具有取向结构的肩袖补片的孔径为10-200μm，取向度为0-180°。
优选地，步骤(5)中，低温冷冻干燥的温度为(-80)-(-30)℃。
作为第二方面，本发明提供了一种具有取向结构的肩袖补片，其由上述的制备方法得到。
由于采用上述方案，本发明的有益效果是：
溶剂在冷冻过程中到达共晶点时形成共晶体，随着温度进一步降低，溶液将发生玻璃化转变，结晶形状也可能发生改变，这一过程会使样品在冷冻干燥过程中孔径发生变化，通过调控冷冻温度(即结晶温度)可以调控孔径。同时冷冻干燥过程中降温温度和速度对样品冷冻干燥时样品结构的稳定性有很大影响，因此本发明通过调控定向结晶技术中的结晶温度和冷冻干燥降温速率，制备具有适宜孔径以及取向度的肩袖补片，目前已广泛应用于组织工程修复研究和临床肩袖修复，具有良好的生物力学性能和生物相容性，可用于肩袖损组织伤疾病的再生治疗；另外，本发明的材料来源广泛，制备方法简单高效，价格低廉，具有良好的临床应用前景。
附图说明
图1为本发明的实施例1中取向结构肩袖补片SEM示意图。
具体实施方式
本发明提供了一种具有取向结构的肩袖补片及其制备方法。
以下结合附图和实施例对本发明作进一步的说明。
实施例1：
将蚕丝蛋白(即丝素蛋白)配制成10％质量体积浓度的水溶液中得到第一混合液，将蚕丝蛋白溶于乙酸水溶液中，加入IGF-2，得到第二混合液，将第一混合液浇筑于方形模具中，利用定向结晶技术，置于-80℃进行定向结晶12h，得到冷冻固态物，将第二混合液浇筑于冷冻固态物预冻，得到预冻样品，转移入冷冻干燥机中，梯度降温至-30℃进行冷冻干燥，抽真空48h，最终获得具有取向结构的肩袖补片。
实施例2：
将蚕丝蛋白配制成10％质量体积浓度的水溶液，浇筑于方形模具中，将蚕丝蛋白溶液置于恒温-20℃的冷冻箱中进行定向结晶12h得到冷冻固态物；将蚕丝蛋白配制成10％质量体积浓度的水溶液后加入BMP-2，混合均匀制得第二混合液，将第二混合液浇筑到冷冻固态物后，快速转移至-80℃冷冻2h，转移入冷冻干燥机中，按照1℃/h的速度进行降温，降温至-80℃进行冷冻干燥，抽真空48h，最终获得具有取向结构的肩袖补片。
实施例3：
将蚕丝蛋白配制成5％质量体积浓度的水溶液，浇筑于方形模具中，将蚕丝蛋白溶液置于-20℃恒温冷冻1h，再按照5℃/h速度降温至-50℃结晶12h得到冷冻固态物；将蚕丝蛋白配制成5％质量体积浓度的水溶液后加入BMP-2，混合均匀制得第二混合液，将第二混合液快速浇筑到冷冻固态物上得到预冻样品，将预冻样品转移至-80℃冷冻2h后转移入冷冻干燥机中，按照1℃/h的速度进行降温，降温至-50℃进行冷冻干燥，抽真空48h，最终获得具有取向结构的肩袖补片。
上述对实施例的描述是为了便于该技术领域的普通技术人员能理解和使用本发明。熟悉本领域技术人员显然可以容易的对这些实施例做出各种修改，并把在此说明的一般原理应用到其他实施例中，而不必经过创造性的劳动。因此，本发明不限于上述实施例。本领域技术人员根据本发明的原理，不脱离本发明的范畴所做出的改进和修改都应该在本发明的保护范围之内。

Claims (10)

  1. 一种具有取向结构的肩袖补片的制备方法，其特征在于：其包括如下步骤：
    (1)、将天然源基质材料加入溶剂中得到第一混合液；
    (2)、将天然源基质材料加入溶剂中，混合均匀后加入成骨因子，得到第二混合液；
    (3)、将所述第一混合液浇筑于模具中，定向结晶，结晶后得到冷冻固态物；
    (4)、将所述第二混合液浇筑于步骤(3)的冷冻固态物上，进行预冻，得到预冻样品；
    (5)、将所述预冻样品低温冷冻干燥，得到具有取向结构的肩袖补片。
  2. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(1)和步骤(2)中，所述天然源基质材料选自胶原、明胶、丝素蛋白、壳聚糖、乳糖和氨糖中的一种以上。
  3. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(1)和步骤(2)中，所述溶剂选自六氟异丙醇、三氟乙酸、超纯水和乙酸水溶液中的一种以上。
  4. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(1)和步骤(2)中，所述第一混合液和第二混合液的质量体积浓度均为1-20％。
  5. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(2)中，所述成骨因子选自骨形态发生蛋白、碱性成纤维细胞生长因子、胰岛素样生长因子、Nell-1、去铁胺和RGD短肽中的一种以上。
  6. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(3)中，所述定向结晶的温度为(-200)-(-20)℃，时间为12-24h。
  7. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(4)中，所述预冻样品的厚度为0.1-10mm。
  8. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(5)中，所述具有取向结构的肩袖补片的孔径为10-200μm，取向度为0-180°。
  9. 根据权利要求1所述的具有取向结构的肩袖补片的制备方法，其特征在于：步骤(5)中，所述低温冷冻干燥的温度为(-80)-(-30)℃。
  10. 一种具有取向结构的肩袖补片，其特征在于：其由权利要求1-9任一项所述的制备方法得到。
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