WO2019227835A1 - 一种微区电势差异性骨植入材料及其制备方法 - Google Patents

一种微区电势差异性骨植入材料及其制备方法 Download PDF

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WO2019227835A1
WO2019227835A1 PCT/CN2018/111947 CN2018111947W WO2019227835A1 WO 2019227835 A1 WO2019227835 A1 WO 2019227835A1 CN 2018111947 W CN2018111947 W CN 2018111947W WO 2019227835 A1 WO2019227835 A1 WO 2019227835A1
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region
area
polarized
micro
depolarized
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French (fr)
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宁成云
于鹏
王珍高
周正难
黎昌昊
张珂嘉
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华南理工大学
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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • 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
    • 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
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • H—ELECTRICITY
    • H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10N—ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
    • H10N30/00—Piezoelectric or electrostrictive devices
    • H10N30/01—Manufacture or treatment
    • H10N30/04—Treatments to modify a piezoelectric or electrostrictive property, e.g. polarisation characteristics, vibration characteristics or mode tuning
    • H10N30/045—Treatments to modify a piezoelectric or electrostrictive property, e.g. polarisation characteristics, vibration characteristics or mode tuning by polarising
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • 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
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the invention belongs to the technical field of biomedical materials, and particularly relates to a micro-area potential difference bone implant material and a preparation method thereof.
  • Natural bone tissue is piezoelectric and originates from the linearly arranged collagen molecules in the bone. This piezoelectric characteristic is of great significance for both bone growth and reconstruction.
  • the piezoelectric collagen molecules in human bones are assembled into collagen fibers and further biomineralized to form a multi-stage bone structure.
  • collagen and other proteins are first assembled into nano-scale collagen fibers, and then the collagen fibers are further assembled into collagen. Bundle, eventually forming dense or loose bone tissue. Therefore, bone itself is a space-specific electrical functional material composed of micro-scale distributed piezoelectric responsive structures. This spatially specific bone structure can achieve force-electric conversion, apply electrical stimulation to bone cells, and regulate the osteogenesis process.
  • the results of the above basic research have important guiding significance for bionic construction of bone implant materials with spatial piezoelectric characteristics.
  • bio-piezoelectric materials such as potassium sodium niobate, barium titanate, lithium niobate and polyvinylidene fluoride have been developed and applied in the field of bone repair research.
  • Some studies have used hydroxyapatite and barium titanate to construct new implant materials, and use ice templates to construct porous scaffolds with different porosities with elongated pore structure. The results also show that the scaffolds can significantly increase Cell proliferation and osteogenic differentiation, but this study suggests that polarized and unpolarized piezoelectric scaffolds have little effect on osteogenesis.
  • studies have also added barium titanate as an additive to titanium dioxide materials to promote the proliferation of osteoblasts on the surface of the material.
  • the object of the present invention is to provide a microregion potential difference bone implant material and a preparation method thereof.
  • the piezoelectric material is subjected to polarization treatment, and then the partially polarized piezoelectric material area is depolarized.
  • the piezoelectric material forms a polarized area and a depolarized area.
  • the depolarized area preferably forms a periodic arrangement.
  • a micro-area potential difference is formed between the depolarized area and the depolarized area, thereby obtaining a micro-area-differential potential bone implant material.
  • the bone implant material of the present invention has a significant bone-promoting effect.
  • a method for preparing a bone implant material with different micro-area potentials includes the following steps:
  • the bone implant material is composed of a polarized region and a depolarized region; the polarized region is in phase with the depolarized region.
  • the polarized region and the depolarized region is a plurality of independent regions, and each of the plurality of independent regions is a microregion.
  • the microregion refers to the width of the independent region, The diameter and / or area is on the order of micrometers.
  • Width refers to the distance between two opposing straight lines or curves. The distance between these two opposing straight lines or curves is smaller than the distance of other relative straight lines or curves forming the area. For example: if the area is rectangular, the width is micron level; if the area is circular, the diameter is micron level; if the area is oval, the short axis is micron level.
  • both the polarized region and the depolarized region are multiple independent regions, the polarized region and the depolarized region are arranged alternately or periodically.
  • the depolarized area is a whole area and the depolarized area is a plurality of independent areas, the depolarized areas are periodically arranged, and the periphery of each depolarized area is a polarized area.
  • the polarization is a high-voltage polarization, and the conditions for the polarization are a polarization voltage of 0.5-20kV / cm and a polarization processing time of 5-30min;
  • the piezoelectric material is one or more of potassium sodium niobate, barium titanate-based, lithium niobate-based, or polyvinylidene fluoride piezoelectric materials;
  • the piezoelectric material in step (1) is in a sheet shape
  • the depolarization processing in step (2) refers to using a fiber laser to perform laser processing on a part of the polarized piezoelectric material to depolarize the part;
  • the laser processing conditions are: the laser power is 1-8W, and the scanning speed is 50-200mm / s.
  • the surface potential difference between the depolarized region and the adjacent polarized region in step (2) is 10-1000mV.
  • the thickness is preferably 1 to 200 ⁇ m.
  • the depolarization process in step (2) refers to a depolarization process using a laser, which is a fiber laser, a gas laser, a solid-state laser, or a semiconductor laser.
  • micro-area potential difference bone implant material is prepared by the above method.
  • the invention is realized by focusing the laser beam to select a region to induce depolarization to change the microdomain electrical domain orientation of the bioactive piezoelectric material, thereby changing the surface potential of the microregion.
  • most bone implant materials are mainly designed around the composition and structure of bone, and the role of electrical signals in osteogenesis is often ignored.
  • the study found that the bone itself is piezoelectric, and there is a bone matrix micro-area electrical environment formed by spatially arranged piezoelectric collagen fibers and non-piezoelectric structures in the bone.
  • the micro-region piezoelectric differential bone implant material constructed by the invention can simulate the intra-osseous electrophysiological micro-environment to apply electrical signals to the cells and regulate the osteogenic differentiation and osteointegration process of bone marrow mesenchymal stem cells.
  • the micro-area potential difference implant material prepared by the invention can simulate the spatial distribution characteristics of the micro-area potential of bone tissue, simulate the electrophysiological micro-environment in bone, and has a significant bone-promoting effect.
  • the present invention has the following advantages and beneficial effects:
  • the bone implant material of the present invention can simulate the electrical environment of the bone matrix microregion formed by spatially arranged piezoelectric collagen fibers and non-piezoelectric structures in the bone, apply electrical signals to the cells, and regulate the formation of bone marrow mesenchymal stem cells. Bone differentiation and osseointegration process.
  • the bone implant material of the present invention has a significant bone-promoting effect.
  • the method of the invention is simple and efficient, and realizes the construction of fast, efficient and accurate bone-like micro-region electrical environment implant material.
  • FIG. 1 is a schematic diagram of electrical characteristics of a micro-area potential difference implant material according to the present invention
  • FIG. 2 is a scanning electron micrograph of polarized potassium sodium niobate and microdomain-induced depolarized potassium sodium niobate in Example 1; (a) is an SEM image of polarized potassium sodium niobate, and (b) laser-induced micro SEM image of depolarized potassium sodium niobate;
  • Example 3 is a Kelvin force microscopy surface potential diagram of a bone implant material with a difference in micro-area potential in Example 1; (a) a surface potential diagram of a micro-area not affected by laser light, and (b) a surface potential diagram of a micro-area affected by laser;
  • Example 4 is an alkaline phosphatase staining diagram of a micro-area potential-differential bone implant material of Example 1; (a) a micro-area potential-differential bone implant material, and (b) a bioactive hydroxyapatite material.
  • the present invention provides a method for preparing a micro-area potential difference bone implant material.
  • the micro-area thermal effect of the focused laser beam is used to induce the de-polarization of the micro-area on the surface of the polarized piezoelectric material, thereby changing the micro-domain electrical domain orientation of the bioactive piezoelectric material, and then changing the micro-area potential of the material surface.
  • FIG. 1 The schematic diagram of the electrical characteristics of the micro-area potential-differential implant material of the present invention is shown in FIG. 1, in which the electric domain orientation (polarized area) of the laser-unacted micro-area tends to be uniform due to the pre-external electric field polarization and the surface is positively charged ; Laser-acting microdomains (depolarized regions) are depolarized due to laser thermal effects, the domain orientation is disordered, and the surface has a relatively small amount of positive charge.
  • a method for preparing a bone implant material with different micro-area potentials includes the following steps:
  • the fiber laser and use the fiber laser to perform micro-area laser processing on the polarized piezoelectric material to induce de-polarization of the micro-area to build a bone-implant material with different potentials in the micro-area;
  • the conditions of de-polarization are: laser
  • the power is 3W
  • the scanning speed is 100mm / s
  • the scanning path is a stripe with periodic intervals of 100 ⁇ m.
  • the bone implant material is composed of a stripe-shaped polarized region and a depolarized region.
  • the polarized region and depolarized region The width of the area is 100 ⁇ m.
  • the scanning electron microscope morphology of the bone implant material in this example is shown in Fig. 2, where (a) is a SEM image of polarized potassium sodium niobate, and (b) is a SEM image of laser-induced depolarization of potassium sodium niobate. . Laser effect did not cause the surface morphology of the material to change. After depolarization, the piezoelectric constant of the micro-region is reduced to zero, and a potential difference is formed between the polarized region and the depolarized region.
  • FIG. 3 is a Kelvin force microscopy surface potential diagram of a bone implant material with micro-area potential difference in Example 1; (a) a surface potential diagram of a micro-area not affected by a laser, and (b) a surface potential diagram of a micro-area subjected to a laser.
  • the micro-area potential difference implant material prepared in this embodiment can simulate the spatial distribution characteristics of the surface potential of bone tissue, simulate the electrophysiological microenvironment in bone, and has a significant bone-promoting effect (Figure 4).
  • 4 is an alkaline phosphatase staining diagram of a micro-area potential-differential bone implant material of Example 1; (a) a micro-area potential-differential bone implant material, and (b) a bioactive hydroxyapatite material.
  • the micropotential-differential bone implant material can significantly promote the expression of alkaline phosphatase in bone marrow mesenchymal stem cells, thereby promoting osteogenic differentiation (cell seeding density of 10000 / mL, and cell culture time of 7 days).
  • a method for preparing a bone implant material with different micro-area potentials includes the following steps:
  • the fiber laser and use the fiber laser to perform micro-area laser processing on the polarized piezoelectric material to induce de-polarization of the micro-area to build a bone-implant material with different potentials in the micro-area;
  • the conditions of de-polarization are: laser
  • the power is 3W
  • the scanning speed is 100mm / s
  • the scanning path is a stripe with periodic intervals of 100 ⁇ m.
  • the bone implant material is composed of a stripe-shaped polarized region and a depolarized region.
  • the polarized region and depolarized region The width of the area is 100 ⁇ m.
  • the polarized region is adjacent to the depolarized region, the surface potential difference between adjacent micro-regions is ⁇ 300 mV, and the micro-region width is 100 ⁇ m.
  • a method for preparing a bone implant material with different micro-area potentials includes the following steps:
  • the fiber laser and use the fiber laser to perform micro-area laser processing on the polarized piezoelectric material to induce de-polarization of the micro-area to build a bone-implant material with different potentials in the micro-area;
  • the conditions of de-polarization are: laser The power is 3W, the scanning speed is 100mm / s, and the scanning path is a periodically arranged circular micro-area, the center distance is 200 ⁇ m, and the diameter of the circle is 100 ⁇ m;
  • the bone implant material consists of a polarized area and a periodically distributed circle It is composed of depolarized regions, each depolarized region has a diameter of 100 ⁇ m, and the center-to-center spacing of the depolarized regions is 200 ⁇ m.
  • the polarized region is adjacent to the depolarized region, and the surface potential difference between adjacent microregions is ⁇ 600mV.
  • a method for preparing a bone implant material with different micro-area potentials includes the following steps:
  • the fiber laser and use the fiber laser to perform micro-area laser processing on the polarized piezoelectric material to induce de-polarization of the micro-area to build a bone-implant material with different potentials in the micro-area;
  • the conditions of de-polarization are: laser
  • the power is 1W
  • the scanning speed is 100mm / s
  • the scanning path is a stripe with periodic intervals of 100 ⁇ m.
  • the bone implant material is composed of a stripe-shaped polarized region and a depolarized region.
  • the polarized region and depolarized region The width of the area is 100 ⁇ m.
  • the polarized region is adjacent to the depolarized region, the surface potential difference between adjacent micro-regions is ⁇ 200 mV, and the micro-region width is 100 ⁇ m.

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Abstract

一种微区电势差异性骨植入材料及其制备方法，属于生物医用材料的技术领域。所述方法为：(1)将压电材料进行极化处理，得到极化压电材料；(2)将极化压电材料的部分区域进行去极化处理，获得骨植入材料；此时骨植入材料由极化区域和去极化区域组成；极化区域与去极化区域相邻，所述极化区域和去极化区域中至少有一种区域为多个独立的区域，所述多个独立区域中每一独立区域为微区，所述微区是指独立区域的宽度、直径和/或面积为微米级。骨植入材料具有微区电势差，可模拟骨组织微区电势的空间分布特征，模拟骨内电生理微环境，具有显著的促成骨效果。

Description

一种微区电势差异性骨植入材料及其制备方法 技术领域
本发明属于生物医用材料技术领域，具体涉及一种微区电势差异性骨植入材料及其制备方法。
背景技术
天然骨组织具有压电性，来源于骨内线性排列的胶原分子，该压电特性对骨生长和重建过程都具有重要的意义。人体骨内的压电性胶原分子组装成为胶原纤维并进一步进行生物矿化组装形成多级骨结构，在骨内胶原和其他蛋白首先进行纳米级组装成为胶原纤维，再由胶原纤维进一步组装为胶原束，最终形成致密或者疏松的骨组织。因此，骨本身是一种由微米尺度分布的压电响应性结构组成的空间特异性的电学功能材料。这种具有空间特异性的骨结构可实现力电转换，对骨细胞施加电刺激，调控成骨过程。上述基础研究的成果对仿生构建具有空间压电特性的骨植入材料具有重要的指导意义。
目前，已开发出铌酸钾钠基、钛酸钡基、铌酸锂基和聚偏氟乙烯基等生物压电材料，应用于骨修复研究领域。有研究利用羟基磷灰石和钛酸钡进行复合构建新型植入体材料，并通过冰模板的方法构建具有伸长孔径结构的不同孔隙率的多孔支架，其研究结果也表明该支架可以显著增加细胞增殖和成骨分化，但是该研究认为极化和未极化压电支架对成骨性能影响不大。此外，也有研究将钛酸钡作为添加剂加入到二氧化钛材料中，起到促进材料表面成骨细胞的增殖的作用。除用作块体直接植入以外，还有研究将钛酸钡的微米颗粒嵌入柔性基底，构建压电功能膜。如静电纺丝聚己内酯支架中添加钛酸钡，可以促进前成骨细胞的骨钙素基因的表达。上述评述表明，尚未有研究构建具有微区电势差异的功能微区用以促进成骨分化。
发明内容
为了克服现有技术的缺点和不足，也为了模拟由微米尺度组装的胶原纤维形成的体内压电性微区结构，本发明的目的在于提供一种微区电势差异性骨植 入材料及其制备方法。本发明将压电材料进行极化处理，然后将部分极化压电材料区域进行去极化，压电材料形成了极化区域和去极化区域，去极化区域优选形成周期性排列，极化区域与去极化区域之间形成微区电势差，从而获得微区电势差异性骨植入材料。本发明的骨植入材料具有显著的促成骨效果。
本发明目的是通过下述技术方案实现：
一种微区电势差异性的骨植入材料的制备方法，包括以下步骤：
(1)将压电材料进行极化处理，得到极化压电材料；
(2)将极化压电材料的部分区域进行去极化处理，获得骨植入材料；此时骨植入材料由极化区域和去极化区域组成；极化区域与去极化区域相邻，所述极化区域和去极化区域中至少有一种区域为多个独立的区域，所述多个独立区域中每一独立区域为微区，所述微区是指独立区域的宽度、直径和/或面积为微米级。
宽度是指两条相对直线或曲线间的距离，这两条相对的直线或曲线的间距离相较于形成区域的其他相对直线或曲线的距离要小。如：区域为长方形，则宽为微米级；区域为圆形，则直径为微米级；区域为椭圆形，则短轴为微米级。
当极化区域和去极化区域都为多个独立的区域时，极化区域与去极化区域相间排列或周期性排列。
当极化区域为整体区域，去极化区域为多个独立区域时，去极化区域周期性排列，每一去极化区域的四周为极化区域。
所述极化为高压极化，极化的条件为极化电压为0.5-20kV/cm，极化处理时间为5-30min；
所述压电材料为铌酸钾钠、钛酸钡基、铌酸锂基或聚偏氟乙烯压电材料中一种以上；
步骤(1)中所述压电材料为片状；
步骤(2)中所述去极化处理是指采用光纤激光器对极化压电材料的部分区域进行激光处理，使部分区域去极化；
激光处理的条件为激光功率为1-8W，扫描速度50-200mm/s。
步骤(2)中去极化区域与相邻极化区域的表面电势差为10-1000mV。
步骤(2)中宽度、直径为微米级时，优选为1-200μm。
步骤(2)中去极化处理是指采用激光器进行去极化处理，所述激光器为光纤激光器、气体激光器、固体激光器或半导体激光器。
所述微区电势差异性的骨植入材料通过上述方法制备得到。
本发明通过聚焦激光束选区诱导去极化改变生物活性压电材料的微区电畴取向进而改变微区表面电势的方式实现。当前多数骨植入材料主要围绕骨的成分和结构进行仿生设计，电信号在成骨过程中的作用往往被忽视。研究发现骨本身具有压电性，在骨内存在由空间周期性排列的压电性胶原纤维和非压电性结构形成的骨基质微区电学环境。本发明构建的微区压电差异性骨植入材料，可模拟骨内电生理微环境对细胞施加电信号，调控骨髓间充质干细胞成骨分化和骨整合过程。
本发明所制备的微区电势差异性植入材料，可模拟骨组织微区电势的空间分布特征，模拟骨内电生理微环境，具有显著的促成骨效果。
与现有技术相比，本发明具有以下优点和有益效果：
本发明的骨植入材料可模拟骨内由空间周期性排列的压电性胶原纤维和非压电性结构形成的骨基质微区电学环境，对细胞施加电信号，调控骨髓间充质干细胞成骨分化和骨整合过程。本发明的骨植入材料具有显著的促成骨效果。本发明方法的简单、高效，实现了快速、高效、精确仿骨微区电学环境植入材料的构建。
附图说明
图1为本发明的微区电势差异性植入材料的电学特性示意图；
图2为实施例1中极化铌酸钾钠和微区诱导去极化铌酸钾钠的扫描电镜图；其中(a)为极化铌酸钾钠的SEM图，(b)激光诱导微区去极化铌酸钾钠的SEM图；
图3为实施例1的微区电势差异性的骨植入材料的开尔文力显微镜测表面电势图；(a)激光未作用微区的表面电势图，(b)激光作用微区的表面电势图；
图4为实施例1的微区电势差异性的骨植入材料的碱性磷酸酶染色图；(a)微区电势差异性骨植入材料，(b)生物活性羟基磷灰石材料。
具体实施方式
下面结合实施例和附图对本发明作进一步详细的描述，但本发明的实施方 式不限于此。为模拟由微米尺度组装的胶原纤维形成的体内微区电势差异结构，本发明提供一种制备微区电势差异性骨植入材料的方法。本方法通过聚焦激光束的微区热效应在极化的压电材料表面选区诱导微区去极化，改变生物活性压电材料的微区电畴取向，进而改变材料表面微区电势。
本发明的微区电势差异性植入材料的电学特性示意图如图1所示，其中激光未作用微区电畴取向(极化区域)由于前期的外加电场极化作用趋于一致，表面带正电荷；激光作用微区(去极化区域)则由于激光热作用导致微区去极化，电畴取向杂乱无章，表面相对正电荷量少。
实施例1
一种微区电势差异性的骨植入材料的制备方法，包括以下步骤：
(1)利用砂纸对生物压电材料铌酸钾钠进行梯度打磨、去离子水清洗并真空干燥；降低压电材料表面粗糙度，去离子水超声清洗为去除材料表面黏附的砂纸纳米颗粒；
(2)将铌酸钾钠压电材料在油浴中进行高压极化，得到极化压电材料，高压极化的条件为：极化电场为2kV/cm，极化处理时间为15min；
(3)对光纤激光器进行聚焦，使用光纤激光器对极化压电材料进行微区激光处理，引发微区去极化以构建微区电势差异性的骨植入材料；去极化的条件为：激光功率为3W，扫描速度100mm/s，扫描路径为周期性100μm间隔分布的条纹；所述骨植入材料由间隔分布条纹状的极化区域和去极化区域组成，极化区域和去极化区域的宽度为100μm。
本实施例的骨植入材料扫描电镜形貌如图2所示，其中(a)为极化铌酸钾钠的SEM图，(b)激光诱导微区去极化铌酸钾钠的SEM图。激光作用未引起材料表面形貌变化。去极化后微区的压电常数降为零，极化区域与去极化区域形成电势差。
本实施例的骨植入材料中极化区域与去极化区域相邻，相邻微区表面电势差异为～600mV(图3)，微区宽度为100μm。图3为实施例1的微区电势差异性的骨植入材料的开尔文力显微镜测表面电势图；(a)激光未作用微区的表面电势图，(b)激光作用微区的表面电势图。
本实施例所制备的微区电势差异性植入材料，可模拟骨组织表面电势的空间分布特征，模拟骨内电生理微环境，具有显著的促成骨效果(图4)。图4为实施例1的微区电势差异性的骨植入材料的碱性磷酸酶染色图；(a)微区电势差异性骨植入材料，(b)生物活性羟基磷灰石材料。微区电势差异性骨植入材料可显著促进骨髓间充质干细胞碱性磷酸酶表达，从而促进成骨分化(细胞接种密度10000/mL,细胞培养时间7天)。
实施例2
一种微区电势差异性的骨植入材料的制备方法，包括以下步骤：
(1)利用砂纸对生物压电材料铌酸钾钠进行梯度打磨、去离子水清洗并真空干燥；降低压电材料表面粗糙度，去离子水超声清洗为去除材料表面黏附的砂纸纳米颗粒；
(2)将铌酸钾钠压电材料在油浴中进行高压极化，得到极化压电材料，高压极化的条件为：极化电场为1.5kV/cm，极化处理时间为15min；
(3)对光纤激光器进行聚焦，使用光纤激光器对极化压电材料进行微区激光处理，引发微区去极化以构建微区电势差异性的骨植入材料；去极化的条件为：激光功率为3W，扫描速度100mm/s，扫描路径为周期性100μm间隔分布的条纹；所述骨植入材料由间隔分布条纹状的极化区域和去极化区域组成，极化区域和去极化区域的宽度为100μm。
本实施例的骨植入材料中极化区域与去极化区域相邻，相邻微区表面电势差异为～300mV，微区宽度为100μm。
实施例3
一种微区电势差异性的骨植入材料的制备方法，包括以下步骤：
(1)利用砂纸对生物压电材料铌酸钾钠进行梯度打磨、去离子水清洗并真空干燥；降低压电材料表面粗糙度，去离子水超声清洗为去除材料表面黏附的砂纸纳米颗粒；
(2)将铌酸钾钠压电材料在油浴中进行高压极化，得到极化压电材料，高压极化的条件为：极化电场为2kV/cm，极化处理时间为15min；
(3)对光纤激光器进行聚焦，使用光纤激光器对极化压电材料进行微区激光处理，引发微区去极化以构建微区电势差异性的骨植入材料；去极化的条件 为：激光功率为3W，扫描速度100mm/s，扫描路径为周期性排布的圆形微区，圆心间距为200μm，圆的直径为100μm；所述骨植入材料由极化区域和周期性分布圆形去极化区域组成，每一去极化区域直径为100μm，去极化区域的圆心间距为200μm。
本实施例的骨植入材料中极化区域与去极化区域相邻，相邻微区表面电势差异为～600mV。
实施例4
一种微区电势差异性的骨植入材料的制备方法，包括以下步骤：
(1)旋涂法制备聚偏氟乙烯薄膜，去离子水清洗并真空干燥；
(2)将聚偏氟乙烯压电材料在油浴中进行高压极化，得到极化压电材料，高压极化的条件为：极化电场为0.5kV/cm，极化处理时间为20min；
(3)对光纤激光器进行聚焦，使用光纤激光器对极化压电材料进行微区激光处理，引发微区去极化以构建微区电势差异性的骨植入材料；去极化的条件为：激光功率为1W，扫描速度100mm/s，扫描路径为周期性100μm间隔分布的条纹；所述骨植入材料由间隔分布条纹状的极化区域和去极化区域组成，极化区域和去极化区域的宽度为100μm。
本实施例的骨植入材料中极化区域与去极化区域相邻，相邻微区表面电势差异为～200mV，微区宽度为100μm。

Claims (8)

  1. 一种微区电势差异性的骨植入材料的制备方法，其特征在于：包括以下步骤：
    (1)将压电材料进行极化处理，得到极化压电材料；
    (2)将极化压电材料的部分区域进行去极化处理，获得骨植入材料；此时骨植入材料由极化区域和去极化区域组成；极化区域与去极化区域相邻，所述极化区域和去极化区域中至少有一种区域为多个独立的区域，所述多个独立区域中每一独立区域为微区，所述微区是指独立区域的宽度、直径和/或面积为微米级。
  2. 根据权利要求1所述微区电势差异性的骨植入材料的制备方法，其特征在于：当极化区域和去极化区域都为多个独立的区域时，极化区域与去极化区域相间排列或周期性排列；
    当极化区域为整体区域，去极化区域为多个独立区域时，去极化区域周期性排列，每一去极化区域的四周为极化区域。
  3. 根据权利要求1所述微区电势差异性的骨植入材料的制备方法，其特征在于：所述极化为高压极化，极化的条件为极化电压为0.5-20kV/cm，极化处理时间为5-30min。
  4. 根据权利要求1所述微区电势差异性的骨植入材料的制备方法，其特征在于：所述压电材料为铌酸钾钠、钛酸钡基、铌酸锂基或聚偏氟乙烯压电材料中一种以上；步骤(1)中所述压电材料为片状。
  5. 根据权利要求1所述微区电势差异性的骨植入材料的制备方法，其特征在于：步骤(2)中所述去极化处理是指采用激光器对极化压电材料的部分区域进行激光处理，使部分区域去极化。
  6. 根据权利要求5所述微区电势差异性的骨植入材料的制备方法，其特征在于：激光处理的条件为激光功率为1-8W，扫描速度50-200mm/s。
  7. 根据权利要求1所述微区电势差异性的骨植入材料的制备方法，其特征在于：步骤(2)中去极化区域与相邻极化区域的表面电势差为10-1000mV；
    步骤(2)中宽度、直径为微米级时，宽度或直径为1-200μm。
  8. 一种由权利要求1～7任一项所述制备方法得到的微区电势差异性的骨植入材料。
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