技术领域Technical Field
本发明属于人工椎间盘技术领域，尤其涉及一种传感式水凝胶人工椎间盘及其制备方法。The invention belongs to the technical field of artificial intervertebral discs, and in particular relates to a sensing hydrogel artificial intervertebral disc and a preparation method thereof.
背景技术Background Art
本部分的陈述仅仅是提供了与本发明相关的背景技术信息，不必然构成在先技术。The statements in this section merely provide background information related to the present invention and do not necessarily constitute prior art.
椎间盘是连接相邻两个椎体的纤维软骨盘，由外围纤维环和中心的髓核组成。纤维环由多层交错排列的纤维软骨环组成，具有较大的坚韧性和弹性，主要作用为承受压力；髓核的主要成分为蛋白多糖，呈果冻状，给予椎间盘灵活的活动空间。因此，椎间盘是一种具有一定的弹性和韧性，可以在一定程度内变形，以缓冲压力的结缔组织。The intervertebral disc is a fibrocartilage disc that connects two adjacent vertebrae. It is composed of an annulus fibrosus on the periphery and a nucleus pulposus in the center. The annulus fibrosus is composed of multiple layers of staggered fibrocartilage rings, which has great toughness and elasticity and is mainly used to withstand pressure. The main component of the nucleus pulposus is proteoglycan, which is jelly-like and provides the intervertebral disc with flexible space for movement. Therefore, the intervertebral disc is a connective tissue with a certain degree of elasticity and toughness, which can be deformed to a certain extent to buffer pressure.
而椎间盘退行性椎间盘疾病(DDD)是指随着年龄的增长，纤维环和髓核的含水量逐渐减少，髓核张力下降，椎间盘变薄，导致椎间盘结构松弛，在腰椎的外力作用下，导致椎间盘的纤维环破裂，髓核突出引发腰腿痛和神经功能的障碍。目前椎间盘退变疾病的治疗方式分为手术和非手术两种。其中，临床中，脊柱融合手术较简单常见，但该手术会导致颈椎或腰椎活动度丧失，相邻节段应力增加从而加速相邻节段退变等。与传统的脊柱融合术相比，采用可植入式的人工椎间盘支架置换严重退变的天然椎间盘组织是一种新兴的脊柱非融合手术方法，能够保留颈椎或腰椎活动度，减缓相邻锥体节段退变。Degenerative disc disease (DDD) refers to the gradual decrease in the water content of the annulus fibrosus and nucleus pulposus, the decrease in the tension of the nucleus pulposus, the thinning of the intervertebral disc, and the loosening of the intervertebral disc structure. Under the external force of the lumbar spine, the annulus fibrosus of the intervertebral disc ruptures and the nucleus pulposus protrudes, causing low back pain and neurological dysfunction. Currently, the treatment of degenerative disc disease is divided into two types: surgical and non-surgical. Among them, spinal fusion surgery is relatively simple and common in clinical practice, but this surgery can cause loss of cervical or lumbar mobility, increase stress in adjacent segments, and accelerate the degeneration of adjacent segments. Compared with traditional spinal fusion surgery, the use of an implantable artificial intervertebral disc stent to replace severely degenerated natural intervertebral disc tissue is an emerging non-fusion spinal surgical method that can preserve the mobility of the cervical or lumbar spine and slow down the degeneration of adjacent cone segments.
目前在组织工程中，可植入式的人工椎间盘支架多采用金属、陶瓷或者聚合物材料来构建的，如使用静电纺丝或3D打印技术从结构上来模仿人体天然的椎间盘，但是发明人发现，目前的可植入式的人工椎间盘支架存在以下问题：Currently, in tissue engineering, implantable artificial intervertebral disc stents are mostly constructed using metal, ceramic or polymer materials, such as using electrospinning or 3D printing technology to structurally imitate the natural intervertebral disc of the human body. However, the inventors have found that the current implantable artificial intervertebral disc stents have the following problems:
(1)刚性支架与天然椎间盘的机械模量不匹配，容易与上下锥体及周围组织产生磨损，加速退变。虽然能实现椎间盘最基本的承重要求，但难以模拟人体天然椎间盘的运动特点和生物性能，如，不能模仿人体天然椎间盘组织的粘弹性，不能有效地缓冲压力冲击并均匀分散载荷；而且目前的可植入式的人工椎间盘支架大部分缺乏生物相容性，容易引起周围组织炎症反应。(1) The mechanical modulus of the rigid scaffold does not match that of the natural intervertebral disc, and it is easy to cause wear and tear on the upper and lower cones and surrounding tissues, accelerating degeneration. Although it can meet the most basic load-bearing requirements of the intervertebral disc, it is difficult to simulate the movement characteristics and biological properties of the human body's natural intervertebral disc. For example, it cannot imitate the viscoelasticity of the human body's natural intervertebral disc tissue, cannot effectively buffer pressure shocks and evenly disperse the load; moreover, most of the current implantable artificial intervertebral disc scaffolds lack biocompatibility and are prone to cause inflammatory reactions in surrounding tissues.
(2)目前的人工椎间盘支架大多使用静电纺丝或3D打印技术制造的支架，无法判断其植入后的工作状态，无法定量分析植入后的受力情况；而且使用静电纺丝或3D打印技术制造的人工椎间盘支架工艺复杂，价格昂贵，容易引起椎间盘退行性疾病复发且复发率极高，同时不方便个性化设计。(2) Currently, most artificial intervertebral disc stents are manufactured using electrospinning or 3D printing technology. It is impossible to determine their working status after implantation, and it is impossible to quantitatively analyze the stress conditions after implantation. In addition, artificial intervertebral disc stents manufactured using electrospinning or 3D printing technology have complex processes and are expensive. They are prone to recurrence of intervertebral disc degenerative diseases with an extremely high recurrence rate, and are not convenient for personalized design.
发明内容Summary of the invention
为了解决上述背景技术中存在的至少一项技术问题，本发明提供一种传感式水凝胶人工椎间盘及其制备方法，其能够从结构上模仿了天然椎间盘，具有与人体天然椎间盘组织类似的粘弹性，具备优异的抗压强度和机械抗疲劳特性，能有效地缓冲压力冲击并将载荷均匀分散。In order to solve at least one technical problem existing in the above-mentioned background technology, the present invention provides a sensing hydrogel artificial intervertebral disc and a preparation method thereof, which can imitate the natural intervertebral disc in structure, has viscoelasticity similar to that of natural intervertebral disc tissue of the human body, has excellent compressive strength and mechanical fatigue resistance, can effectively buffer pressure shocks and evenly disperse the load.
为了实现上述目的，本发明采用如下技术方案：In order to achieve the above object, the present invention adopts the following technical solution:
本发明的第一个方面提供一种传感式水凝胶人工椎间盘的制备方法。A first aspect of the present invention provides a method for preparing a sensing hydrogel artificial intervertebral disc.
一种传感式水凝胶人工椎间盘的制备方法，其包括：A method for preparing a sensing hydrogel artificial intervertebral disc, comprising:
将水凝胶材料和水按照预设质量比形成混合预备溶液；The hydrogel material and water are mixed in a preset mass ratio to form a preliminary solution;
在椎间盘模具中对混合预备溶液冻融循环，得到一体化椎间盘状的水凝胶；The mixed prepared solution is freeze-thawed in an intervertebral disc mold to obtain an integrated intervertebral disc-shaped hydrogel;
在一体化椎间盘状的水凝胶中相对应的纤维环侧壁部位及中间髓核部位均涂覆防水层；The corresponding side wall of the annulus fibrosus and the middle nucleus pulposus in the integrated intervertebral disc-shaped hydrogel are coated with a waterproof layer;
将涂覆防水层的一体化椎间盘状的水凝胶进行干燥处理，直至达到预设含水量及初步力学性能要求后，去除防水层；Drying the integrated intervertebral disc-shaped hydrogel coated with the waterproof layer until the preset water content and preliminary mechanical property requirements are reached, and then removing the waterproof layer;
将去除防水层的一体化椎间盘状的水凝胶在盐溶液中再进行水合；The integrated intervertebral disc-shaped hydrogel with the waterproof layer removed is rehydrated in a saline solution;
将水合后的一体化椎间盘状的水凝胶在去离子水中浸泡预设时间后，得到抗压且保持区域各向异性的水凝胶，最终制备出传感式水凝胶人工椎间盘。After the hydrated integrated intervertebral disc-shaped hydrogel is soaked in deionized water for a preset time, a hydrogel that is compressive-resistant and maintains regional anisotropy is obtained, and finally a sensing hydrogel artificial intervertebral disc is prepared.
作为一种实施方式，所述水凝胶材料包括但不限于聚乙烯醇、聚丙烯酰胺、聚乙二醇类聚合物、藻酸盐类化合物、纤维素类化合物、壳聚糖、明胶、琼脂或多肽类化合物以及双网络或多网络凝胶材料中的任意一种或多种。As an embodiment, the hydrogel material includes but is not limited to any one or more of polyvinyl alcohol, polyacrylamide, polyethylene glycol polymers, alginate compounds, cellulose compounds, chitosan, gelatin, agar or polypeptide compounds and double network or multi-network gel materials.
作为一种实施方式，所述水凝胶材料和水的质量比为：0.05-0.2：1。As an embodiment, the mass ratio of the hydrogel material to water is: 0.05-0.2:1.
上述技术方案的优点在于，由于水凝胶材料的含量对人工椎间盘的抗压性能影响显著，水凝胶材料的比例越高，分子链越密集，抗压性能越高，但是超过设定值，比如20％的浓度，水凝胶材料无法全部溶解，因此，水凝胶材料溶液的质量分数具有确定的上限值。The advantage of the above technical solution is that since the content of the hydrogel material has a significant effect on the compressive resistance of the artificial intervertebral disc, the higher the proportion of the hydrogel material, the denser the molecular chains and the higher the compressive resistance. However, if the concentration exceeds the set value, such as 20%, the hydrogel material cannot be completely dissolved. Therefore, the mass fraction of the hydrogel material solution has a certain upper limit.
作为一种实施方式，所述防水层材料包括但不限于Ecoflex有机硅胶材料、共聚物材料、聚酰胺、聚酰亚胺、聚酯类和金属无机材料。进一步的，所述涂覆材料为聚二甲基硅氧烷。As an embodiment, the waterproof layer material includes but is not limited to Ecoflex organic silicone material, copolymer material, polyamide, polyimide, polyester and metal inorganic material. Further, the coating material is polydimethylsiloxane.
作为一种实施方式，所述防水层的厚度为500-1000μm。As an implementation manner, the thickness of the waterproof layer is 500-1000 μm.
其中，利用防水层在干燥过程中分区域调控水凝胶的含水量，以使得一体化椎间盘状的水凝胶在不同的位置形成不同的微结构，从而对不同的区域进行力学性能广泛调控。涂覆防水层的部分水分蒸发较少，干燥完毕后该区域的弹性模量相对较低，防水层的厚度过薄过厚均会影响制备出的人工椎间盘的力学性能。The waterproof layer is used to control the water content of the hydrogel in different regions during the drying process, so that the integrated disc-shaped hydrogel forms different microstructures at different locations, thereby widely controlling the mechanical properties of different regions. The part where the waterproof layer is applied has less water evaporation, and the elastic modulus of this area is relatively low after drying. If the thickness of the waterproof layer is too thin or too thick, it will affect the mechanical properties of the prepared artificial disc.
作为一种实施方式，根据预设含水量及初步力学性能要求，相匹配调整干燥处理的温度范围及干燥时间。As an implementation method, the temperature range and drying time of the drying process are adjusted to match the preset moisture content and the initial mechanical property requirements.
上述技术方案的优点在于，通过调控干燥的温度和时间，能够在一定范围内调控水凝胶的机械性能，达到人工椎间盘即达到天燃椎间盘的含水量，又能达到所需要的力学强度。温度过高水凝胶会再次溶胶化，温度过低水分则蒸发过慢，降低人工椎间盘的制备速度。因此，可根据预设含水量及初步力学性能要求，相匹配调整干燥处理的温度范围及干燥时间。The advantage of the above technical solution is that by adjusting the drying temperature and time, the mechanical properties of the hydrogel can be adjusted within a certain range, so that the water content of the artificial intervertebral disc reaches that of the natural intervertebral disc, and the required mechanical strength can be achieved. If the temperature is too high, the hydrogel will be solubilized again, and if the temperature is too low, the water will evaporate too slowly, reducing the preparation speed of the artificial intervertebral disc. Therefore, the temperature range and drying time of the drying treatment can be adjusted to match the preset water content and the initial mechanical property requirements.
作为一种实施方式，在25℃-70℃条件下进行干燥处理，干燥时间为12-24h。As an implementation mode, the drying process is carried out at 25°C-70°C, and the drying time is 12-24 hours.
作为一种实施方式，所述盐溶液的浓度为0.5-2M。As an embodiment, the concentration of the salt solution is 0.5-2M.
上述技术方案的优点在于，盐溶液作为一种交联剂，可制备不溶于水的聚合物吸附剂。盐溶液的浓度过低会影响导电性从而进一步影响传感性能，过高则会影响人工椎间盘的机械性能，如抗压强度。The advantage of the above technical solution is that the salt solution can be used as a cross-linking agent to prepare a water-insoluble polymer adsorbent. If the concentration of the salt solution is too low, it will affect the conductivity and further affect the sensing performance, while if it is too high, it will affect the mechanical properties of the artificial intervertebral disc, such as compressive strength.
作为一种实施方式，冻融循环过程中冷冻的温度为-40～-5℃，冷冻时间为2-24h。As an embodiment, the freezing temperature during the freeze-thaw cycle is -40 to -5°C, and the freezing time is 2 to 24 hours.
作为一种实施方式，冻融循环的次数为3-11次。As an embodiment, the number of freeze-thaw cycles is 3-11 times.
上述技术方案的优点在于，通过冻融循环使水凝胶材料前驱体溶液实现初步的物理交联，冻融循环的次数和时间会影响水凝胶的聚合效果。The advantage of the above technical solution is that the hydrogel material precursor solution can achieve preliminary physical cross-linking through freeze-thaw cycles, and the number and time of freeze-thaw cycles will affect the polymerization effect of the hydrogel.
本发明的第二个方面提供一种传感式水凝胶人工椎间盘。A second aspect of the present invention provides a sensing hydrogel artificial intervertebral disc.
一种传感式水凝胶人工椎间盘，其采用如上述所述的传感式水凝胶人工椎间盘的制备方法中的步骤制备而成；A sensing hydrogel artificial intervertebral disc, which is prepared by the steps in the method for preparing the sensing hydrogel artificial intervertebral disc as described above;
所述传感式水凝胶人工椎间盘由纤维环部位及髓核部位构成的一体化水凝胶结构；The sensing hydrogel artificial intervertebral disc is an integrated hydrogel structure consisting of an annulus fibrosus part and a nucleus pulposus part;
所述传感式水凝胶人工椎间盘的表面设置有电极，所述电极与监控终端相连。Electrodes are arranged on the surface of the sensing hydrogel artificial intervertebral disc, and the electrodes are connected to a monitoring terminal.
其中，在制备出一种传感式水凝胶人工椎间盘后，在其上下表面固定铜线作为电极传输电信号输出，将电信号无线传输到监控终端。电极连接方式包括但不限于单个位置，多个位置以及阵列式传感输出。通过电极设计达到多向传感监测。Among them, after preparing a sensing hydrogel artificial intervertebral disc, copper wires are fixed on its upper and lower surfaces as electrodes to transmit electrical signal output, and the electrical signal is wirelessly transmitted to the monitoring terminal. The electrode connection method includes but is not limited to single position, multiple positions and array sensing output. Multi-directional sensing monitoring is achieved through electrode design.
作为一种实施方式，所述传感式水凝胶人工椎间盘的表面还包覆/涂覆有防粘连层。As an embodiment, the surface of the sensing hydrogel artificial intervertebral disc is also coated with an anti-adhesion layer.
与现有技术相比，本发明的有益效果是：Compared with the prior art, the present invention has the following beneficial effects:
(1)本发明通过可调控质量比的水凝胶材料与混合，经冻融循环后再定向干燥的方法，以一体成型的方式形成一体化椎间盘状的水凝胶，获得与天然椎间盘组织相匹配的机械模量，而且从结构上模仿了天然椎间盘，具有与人体天然椎间盘组织类似的粘弹性，再集合去除防水层的一体化椎间盘状的水凝胶在盐溶液中的水合及去离子处理，进一步提高了人工椎间盘的抗压能力，能有效地缓冲压力冲击并将载荷均匀分散。与现有技术相比大幅提高了水凝胶的抗压性能和机械抗疲劳特性。(1) The present invention forms an integrated disc-shaped hydrogel by mixing a hydrogel material with an adjustable mass ratio, and then drying it in a directional manner after freeze-thaw cycles, thereby obtaining a mechanical modulus that matches the natural disc tissue. In addition, the structure imitates the natural disc and has a viscoelasticity similar to that of the human body's natural disc tissue. The integrated disc-shaped hydrogel with the waterproof layer removed is hydrated and deionized in a saline solution, further improving the compressive resistance of the artificial disc, effectively buffering pressure shocks and evenly dispersing the load. Compared with the prior art, the compressive resistance and mechanical fatigue resistance of the hydrogel are greatly improved.
(2)本发明的传感式水凝胶人工椎间盘可通过两侧的电极设计，将表面受力情况转换为高分辨率、高灵敏度的电学信号，在不同的压缩力和不同的压缩应变下对应不同的电阻变化，具有较高的响应灵敏度，可以根据电阻变化率，感知脊柱活动过程中椎间盘的多向受力情况，在指导严重椎间盘退变患者术后康复方面具有重要应用前景。(2) The sensing hydrogel artificial intervertebral disc of the present invention can convert the surface force conditions into high-resolution and high-sensitivity electrical signals through the electrode design on both sides. It corresponds to different resistance changes under different compressive forces and different compressive strains. It has high response sensitivity and can sense the multi-directional force conditions of the intervertebral disc during spinal movement based on the resistance change rate. It has important application prospects in guiding the postoperative rehabilitation of patients with severe intervertebral disc degeneration.
(3)本发明的传感式水凝胶人工椎间盘具有良好的生物相容性，并且制造成本低，材料简单易得，工艺步骤简单，容易个性化。改善了水凝胶固有的抗压强度差的问题，发挥类比天然椎间盘的力学支撑作用；而且水凝胶结构的人工椎间盘具有防组织粘连的效果，不易与周围组织形成磨损从而引发炎症反应，避免了髓核膨出的问题。(3) The sensing hydrogel artificial intervertebral disc of the present invention has good biocompatibility, low manufacturing cost, simple and easy-to-obtain materials, simple process steps, and easy personalization. It improves the inherent poor compressive strength of hydrogels and plays a mechanical support role similar to that of natural intervertebral discs; moreover, the artificial intervertebral disc with hydrogel structure has the effect of preventing tissue adhesion, is not easy to form wear with surrounding tissues and thus induce inflammatory response, and avoids the problem of nucleus pulposus bulging.
本发明附加方面的优点将在下面的描述中部分给出，部分将从下面的描述中变得明显，或通过本发明的实践了解到。Advantages of additional aspects of the present invention will be given in part in the following description, and in part will become obvious from the following description, or will be learned through practice of the present invention.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
构成本发明的一部分的说明书附图用来提供对本发明的进一步理解，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。The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.
图1为本发明实施例传感式水凝胶人工椎间盘的制备方法原理图；FIG1 is a schematic diagram of a method for preparing a sensing hydrogel artificial intervertebral disc according to an embodiment of the present invention;
图2为实施例1制备传感式水凝胶人工椎间盘的流程示意图；FIG2 is a schematic diagram of the process of preparing a sensing hydrogel artificial intervertebral disc in Example 1;
图3为实施例2传感式水凝胶人工椎间盘的光学照片；FIG3 is an optical photograph of the sensing hydrogel artificial intervertebral disc of Example 2;
图4为实施例3传感式水凝胶人工椎间盘的压应力应变曲线图；FIG4 is a compressive stress-strain curve diagram of the sensing hydrogel artificial intervertebral disc of Example 3;
图5为实施例3传感式水凝胶人工椎间盘的压缩抗疲劳性能图；FIG5 is a diagram showing the compressive fatigue resistance of the sensing hydrogel artificial intervertebral disc of Example 3;
图6为实施例3传感式水凝胶人工椎间盘在不同压应变下的传感性能图；FIG6 is a diagram showing the sensing performance of the sensing hydrogel artificial intervertebral disc under different compressive strains in Example 3;
图7为实施例3传感式水凝胶人工椎间盘在不同压应力下的传感性能图；FIG7 is a diagram showing the sensing performance of the sensing hydrogel artificial intervertebral disc under different compressive stresses in Example 3;
图8为实施例3传感式水凝胶人工椎间盘的传感性能长循环测试图；FIG8 is a long-cycle test diagram of the sensing performance of the sensing hydrogel artificial intervertebral disc of Example 3;
图9为实施例4传感式水凝胶人工椎间盘植入到脊柱模型中替代原有椎间盘的体外传感性能图。FIG. 9 is a graph showing the in vitro sensing performance of the sensing hydrogel artificial intervertebral disc of Example 4 implanted into a spinal model to replace the original intervertebral disc.
具体实施方式DETAILED DESCRIPTION
下面结合附图与实施例对本发明作进一步说明。The present invention will be further described below in conjunction with the accompanying drawings and embodiments.
应该指出，以下详细说明都是例示性的，旨在对本发明提供进一步的说明。除非另有指明，本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。It should be noted that the following detailed descriptions are all illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本发明的示例性实施方式。如在这里所使用的，除非上下文另外明确指出，否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、器件、组件和/或它们的组合。It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and/or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and/or combinations thereof.
本发明为了解决传统椎间盘支架的生物相容性差，不能从宏观结构和生物性能上模仿天然椎间盘，并且缺少对植入人工椎间盘支架的患者进行快速、直接的椎间盘受力情况监测手段的问题，提供了一种传感式水凝胶人工椎间盘及其制备方法。In order to solve the problems that traditional intervertebral disc stents have poor biocompatibility, cannot imitate natural intervertebral discs in terms of macroscopic structure and biological properties, and lack a means to quickly and directly monitor the stress conditions of the intervertebral discs of patients implanted with artificial intervertebral disc stents, the present invention provides a sensing hydrogel artificial intervertebral disc and a preparation method thereof.
下面结合具体实施例来详细说明传感式水凝胶人工椎间盘的制备方法过程。The preparation method of the sensing hydrogel artificial intervertebral disc is described in detail below with reference to specific embodiments.
根据图1，在一个或多个实施例中，提供了一种传感式水凝胶人工椎间盘的制备方法，其包括：According to FIG. 1 , in one or more embodiments, a method for preparing a sensing hydrogel artificial intervertebral disc is provided, which comprises:
步骤S101：将水凝胶材料和水按照预设质量比形成混合预备溶液。Step S101: forming a mixed preliminary solution by mixing a hydrogel material and water according to a preset mass ratio.
在具体实施过程中，所述水凝胶材料为聚乙烯醇、海藻酸钠、聚丙烯酰胺和聚丙烯酸的任一种。In a specific implementation process, the hydrogel material is any one of polyvinyl alcohol, sodium alginate, polyacrylamide and polyacrylic acid.
由于水凝胶材料的含量对人工椎间盘的抗压性能影响显著，水凝胶材料的比例越高，分子链越密集，抗压性能越高，但是超过设定值，比如20％的浓度，水凝胶材料无法全部溶解，因此，水凝胶材料溶液的质量分数具有确定的上限值。如，所述水凝胶材料和水的质量比为：0.05-0.2：1。Since the content of the hydrogel material has a significant effect on the compressive resistance of the artificial intervertebral disc, the higher the proportion of the hydrogel material, the denser the molecular chains, and the higher the compressive resistance. However, if the concentration exceeds the set value, such as 20%, the hydrogel material cannot be completely dissolved. Therefore, the mass fraction of the hydrogel material solution has a certain upper limit. For example, the mass ratio of the hydrogel material to water is: 0.05-0.2:1.
以水凝胶材料为聚乙烯醇为例，聚乙烯醇水凝胶前驱液的制备方法为：将聚乙烯醇粉末分散在去离子水中，在60-100℃下搅拌2-6小时至完全溶解。Taking polyvinyl alcohol as an example of a hydrogel material, the preparation method of the polyvinyl alcohol hydrogel precursor solution is: disperse the polyvinyl alcohol powder in deionized water, and stir at 60-100° C. for 2-6 hours until it is completely dissolved.
优选的，聚乙烯醇溶液的最终质量分数为5-20％。Preferably, the final mass fraction of the polyvinyl alcohol solution is 5-20%.
步骤S102：在椎间盘模具中对混合预备溶液冻融循环，得到一体化椎间盘状的水凝胶。Step S102: freeze-thaw-cycle the mixed prepared solution in the intervertebral disc mold to obtain an integrated intervertebral disc-shaped hydrogel.
在具体实施过程中，冻融循环过程中冷冻的温度为-40～-5℃，冷冻时间为2-24h。冻融循环的次数为3-11次。这样通过冻融循环使水凝胶材料前驱体溶液实现初步的物理交联，冻融循环的次数和时间会影响水凝胶的聚合效果。In the specific implementation process, the freezing temperature during the freeze-thaw cycle is -40 to -5°C, and the freezing time is 2-24 hours. The number of freeze-thaw cycles is 3-11 times. In this way, the hydrogel material precursor solution is initially physically cross-linked through the freeze-thaw cycle, and the number and time of the freeze-thaw cycle will affect the polymerization effect of the hydrogel.
步骤S103：在一体化椎间盘状的水凝胶中相对应的纤维环侧壁部位及中间髓核部位均涂覆防水层。Step S103: a waterproof layer is applied to the corresponding side wall of the annulus fibrosus and the middle nucleus pulposus in the integrated intervertebral disc-shaped hydrogel.
其中，所述防水层的厚度为500-1000μm。Wherein, the thickness of the waterproof layer is 500-1000 μm.
本实施例利用防水层在干燥过程中分区域调控水凝胶的含水量，以使得一体化椎间盘状的水凝胶在不同的位置形成不同的微结构，从而具有不同的力学性能。涂覆防水层的部分水分蒸发较少，干燥完毕后该区域的弹性模量相对较低，防水层的厚度过薄过厚易导致涂覆不均匀，从而影响制备出的人工椎间盘的力学性能。This embodiment uses the waterproof layer to control the water content of the hydrogel in different regions during the drying process, so that the integrated intervertebral disc-shaped hydrogel forms different microstructures at different locations, thereby having different mechanical properties. The part where the waterproof layer is applied evaporates less water, and the elastic modulus of this area is relatively low after drying. If the thickness of the waterproof layer is too thin or too thick, it is easy to cause uneven coating, thereby affecting the mechanical properties of the prepared artificial intervertebral disc.
此处需要说明的是，所述防水层包括但不限于聚二甲基硅氧烷层、聚酰亚胺薄膜和金属薄膜。It should be noted here that the waterproof layer includes but is not limited to a polydimethylsiloxane layer, a polyimide film and a metal film.
步骤S104：将涂覆防水层的一体化椎间盘状的水凝胶进行干燥处理，直至达到预设含水量及初步力学性能要求后，去除防水层。Step S104: Drying the integrated intervertebral disc-shaped hydrogel coated with the waterproof layer until the preset water content and preliminary mechanical property requirements are reached, and then removing the waterproof layer.
在一个或多个实施例中，根据预设含水量及初步力学性能要求，相匹配调整干燥处理的温度范围及干燥时间。In one or more embodiments, the temperature range and drying time of the drying process are adjusted to match the preset moisture content and the initial mechanical property requirements.
例如，在25℃-70℃条件下进行干燥处理，干燥时间为12-24h。For example, the drying process is carried out at 25°C-70°C, and the drying time is 12-24 hours.
本实施例通过调控干燥的温度和时间，能够在一定范围内调控水凝胶的机械性能，达到人工椎间盘即达到天燃椎间盘的含水量，又能达到所需要的力学强度。温度过高水凝胶会再次溶胶化，温度过低水分则蒸发过慢，降低人工椎间盘的制备速度。因此，可根据预设含水量及初步力学性能要求，相匹配调整干燥处理的温度范围及干燥时间。This embodiment can adjust the mechanical properties of the hydrogel within a certain range by adjusting the drying temperature and time, so that the water content of the artificial intervertebral disc reaches that of the natural intervertebral disc, and the required mechanical strength can be achieved. If the temperature is too high, the hydrogel will be solubilized again, and if the temperature is too low, the water will evaporate too slowly, reducing the preparation speed of the artificial intervertebral disc. Therefore, the temperature range and drying time of the drying process can be adjusted to match the preset water content and the initial mechanical property requirements.
步骤S105：将去除防水层的一体化椎间盘状的水凝胶在盐溶液中再进行水合。Step S105: rehydrating the integrated intervertebral disc-shaped hydrogel with the waterproof layer removed in a saline solution.
其中，所述盐溶液的浓度为0.5-2M。盐溶液作为一种交联剂，可制备不溶于水的聚合物吸附剂。盐溶液的浓度过低会影响导电性从而进一步影响传感性能，过高则会影响人工椎间盘的机械性能，如抗压强度。The concentration of the salt solution is 0.5-2 M. As a cross-linking agent, the salt solution can prepare a water-insoluble polymer adsorbent. If the concentration of the salt solution is too low, the conductivity will be affected, which will further affect the sensing performance. If the concentration of the salt solution is too high, the mechanical properties of the artificial intervertebral disc, such as compressive strength, will be affected.
例如，盐溶液可选择柠檬酸钠溶液等盐溶液，本领域技术人员可根据实际情况来具体选择，此处不再详述。For example, the salt solution may be a sodium citrate solution or other salt solution. Those skilled in the art may select a specific salt solution according to actual conditions, which will not be described in detail here.
步骤S106：将水合后的一体化椎间盘状的水凝胶在去离子水中浸泡预设时间后，得到抗压且保持区域各向异性的水凝胶，最终制备出传感式水凝胶人工椎间盘。Step S106: Soaking the hydrated integrated intervertebral disc-shaped hydrogel in deionized water for a preset time to obtain a hydrogel that is compression-resistant and maintains regional anisotropy, and finally preparing a sensing hydrogel artificial intervertebral disc.
下面以水凝胶材料选择聚乙烯醇，防水层选择聚二甲基硅氧烷层，盐溶液选择柠檬酸钠溶液为例，基于不同规格的传感式水凝胶人工椎间盘给出4个不同实施例：Taking polyvinyl alcohol as the hydrogel material, polydimethylsiloxane as the waterproof layer, and sodium citrate as the salt solution as an example, four different embodiments of the sensing hydrogel artificial intervertebral disc with different specifications are given below:
实施例1Example 1
本实施例提供了一种传感式水凝胶人工椎间盘的制备方法，其包括如下步骤：This embodiment provides a method for preparing a sensing hydrogel artificial intervertebral disc, which comprises the following steps:
(1)配制50ml聚乙烯醇(PVA)溶液，聚乙烯醇的质量分数为20wt％，搅拌至完全溶解。(1) Prepare 50 ml of polyvinyl alcohol (PVA) solution with a mass fraction of 20 wt % and stir until it is completely dissolved.
(2)将聚乙烯醇溶液倒入直径为6cm的圆形模具中，模具按照所需形状和大小定制。置于低温环境(-15℃)中冷冻并在室温下解冻，进行冻融循环4次；(2) Pour the polyvinyl alcohol solution into a circular mold with a diameter of 6 cm, which is customized according to the required shape and size. Freeze it in a low temperature environment (-15°C) and thaw it at room temperature, performing freeze-thaw cycles 4 times;
(3)将冻融后得到的圆柱形水凝胶在侧面和表面中间区域涂覆聚二甲基硅氧烷，控制厚度在800μm，中间区域涂覆的直径约为2cm，放入烘箱中，温度设置40℃，干燥24h；(3) The cylindrical hydrogel obtained after freezing and thawing was coated with polydimethylsiloxane on the side and the middle area of the surface, with a thickness of 800 μm and a diameter of about 2 cm in the middle area, and then placed in an oven at 40°C and dried for 24 h;
(4)剥离干燥后水凝胶表面的聚二甲基硅氧烷，在浓度为1M的柠檬酸钠(CA)溶液中浸泡24h进行再水合，进一步提高水凝胶的强度；(4) stripping the polydimethylsiloxane on the surface of the hydrogel after drying and soaking it in a 1 M sodium citrate (CA) solution for 24 h for rehydration to further improve the strength of the hydrogel;
(5)将水合盐析后的水凝胶在去离子水中浸泡12h，以达到平衡，得到抗压且保持区域各向异性的水凝胶，最终制备出传感式水凝胶人工椎间盘。(5) The hydrated and salted-out hydrogel was immersed in deionized water for 12 h to achieve equilibrium, thereby obtaining a hydrogel that is compressive-resistant and maintains regional anisotropy, and finally preparing a sensing hydrogel artificial intervertebral disc.
图2给出的传感式水凝胶人工椎间盘的制备流程示意图，说明制备工艺简单、对实验设备、材料、环境要求低、成本、可调控性强，可重复性高，可大规模批量生产。FIG2 is a schematic diagram of the preparation process of the sensing hydrogel artificial intervertebral disc, which illustrates that the preparation process is simple, has low requirements on experimental equipment, materials, and environment, is cost-effective, has strong controllability, is highly repeatable, and can be mass-produced.
实施例2Example 2
本实施例提供了一种传感式水凝胶人工椎间盘的制备方法，其包括如下步骤：This embodiment provides a method for preparing a sensing hydrogel artificial intervertebral disc, which comprises the following steps:
(1)配制30ml聚乙烯醇(PVA)溶液，聚乙烯醇的质量分数为20wt％，搅拌至完全溶解。(1) Prepare 30 ml of polyvinyl alcohol (PVA) solution with a mass fraction of 20 wt % and stir until it is completely dissolved.
(2)将聚乙烯醇溶液倒入椎间盘型的硅胶模具中，置于低温环境(-15℃)中冷冻并在室温下解冻，进行冻融循环4次；(2) Pour the polyvinyl alcohol solution into a disc-shaped silicone mold, freeze it in a low-temperature environment (-15°C), and thaw it at room temperature, performing freeze-thaw cycles four times;
(3)将冻融后得到的圆柱形水凝胶在侧面和表面中间区域涂覆聚二甲基硅氧烷，控制厚度在800μm，中间区域涂覆的直径约为2cm，放入烘箱中，温度设置40℃，干燥12h；(3) The cylindrical hydrogel obtained after freezing and thawing was coated with polydimethylsiloxane on the side and the middle area of the surface, with a thickness of 800 μm and a diameter of about 2 cm in the middle area, and placed in an oven at 40°C for drying for 12 h;
(4)剥离干燥后水凝胶表面的聚二甲基硅氧烷，在浓度为1M的柠檬酸钠(CA)溶液中浸泡24h进行再水合，进一步提高水凝胶的强度；(4) stripping the polydimethylsiloxane on the surface of the hydrogel after drying and soaking it in a 1 M sodium citrate (CA) solution for 24 h for rehydration to further improve the strength of the hydrogel;
(5)将水合盐析后的水凝胶在去离子水中浸泡12h，以达到平衡，得到抗压且保持区域各向异性的水凝胶，最终制备出传感式水凝胶人工椎间盘。(5) The hydrated and salted-out hydrogel was immersed in deionized water for 12 h to achieve equilibrium, thereby obtaining a hydrogel that is compressive-resistant and maintains regional anisotropy, and finally preparing a sensing hydrogel artificial intervertebral disc.
以尺寸为长径4.5cm，短径为3.5cm的传感式水凝胶人工椎间盘为例：Take the sensor-type hydrogel artificial intervertebral disc with a long diameter of 4.5 cm and a short diameter of 3.5 cm as an example:
图3中的a和b分别为水凝胶椎间盘干燥处理前后的光学照片，图3中的c最终得到的与椎间盘模型类似的水凝胶植入到脊柱模型中的光学照片，处理前传感式水凝胶人工椎间盘尺寸为长径4.5cm，短径3.5cm，厚度为0.9cm，处理后传感式水凝胶人工椎间盘的尺寸为长径4cm，短径3cm，厚度为0.75cm，说明水凝胶干燥处理前后体积有所收缩，获得了较高的机械强度。a and b in Figure 3 are optical photographs of the hydrogel intervertebral disc before and after drying treatment, respectively. c in Figure 3 is an optical photograph of the hydrogel similar to the intervertebral disc model implanted in the spinal model. Before treatment, the dimensions of the sensing hydrogel artificial intervertebral disc were 4.5 cm in long diameter, 3.5 cm in short diameter and 0.9 cm in thickness. After treatment, the dimensions of the sensing hydrogel artificial intervertebral disc were 4 cm in long diameter, 3 cm in short diameter and 0.75 cm in thickness, indicating that the volume of the hydrogel shrunk before and after drying treatment, and a higher mechanical strength was obtained.
实施例3Example 3
本实施例提供了一种传感式水凝胶人工椎间盘的制备方法，其包括如下步骤：This embodiment provides a method for preparing a sensing hydrogel artificial intervertebral disc, which comprises the following steps:
(1)配制50ml聚乙烯醇(PVA)溶液，聚乙烯醇的质量分数为20wt％，搅拌至完全溶解。(1) Prepare 50 ml of polyvinyl alcohol (PVA) solution with a mass fraction of 20 wt % and stir until it is completely dissolved.
(2)将聚乙烯醇溶液倒入尺寸为5*5*1cm的模具中，置于低温环境(-15℃)中冷冻并在室温下解冻，进行冻融循环6次；(2) Pour the polyvinyl alcohol solution into a mold with a size of 5*5*1 cm, freeze it in a low temperature environment (-15°C) and thaw it at room temperature, performing freeze-thaw cycles 6 times;
(3)将冻融后得到的椎间盘型水凝胶在侧面和表面中间区域涂覆聚二甲基硅氧烷，控制厚度在800μm，中间区域涂覆的直径约为2cm，放入烘箱中，温度设置40℃，干燥24h；(3) The intervertebral disc-type hydrogel obtained after freezing and thawing was coated with polydimethylsiloxane on the side and the middle area of the surface, with a thickness of 800 μm and a diameter of about 2 cm in the middle area, and then placed in an oven at 40°C and dried for 24 h;
(4)剥离干燥后水凝胶表面的聚二甲基硅氧烷，在浓度为1M的柠檬酸钠(CA)溶液中浸泡24h进行再水合，进一步提高水凝胶的强度；(4) stripping the polydimethylsiloxane on the surface of the hydrogel after drying and soaking it in a 1 M sodium citrate (CA) solution for 24 h for rehydration to further improve the strength of the hydrogel;
(5)将水合盐析后的水凝胶在去离子水中浸泡24h，以达到平衡，得到抗压且保持区域各向异性的水凝胶，最终制备出传感式水凝胶人工椎间盘。(5) The hydrated and salted-out hydrogel is immersed in deionized water for 24 hours to reach equilibrium, thereby obtaining a hydrogel that is resistant to compression and maintains regional anisotropy, and finally preparing a sensing hydrogel artificial intervertebral disc.
以尺寸为Φ6cm*1cm的传感式水凝胶人工椎间盘为例：Take the sensor-type hydrogel artificial intervertebral disc with a size of Φ6cm*1cm as an example:
图4说明了制备的传感式水凝胶人工椎间盘具有高抗压强度强度和弹性模量。图5说明了在多次循环压缩下，传感式水凝胶人工椎间盘具备良好的抗压缩稳定性，有希望代替人体天然的椎间盘、软骨等承重组织。图6说明了所制备的智能传感式水凝胶人工椎间盘在不同压应变下具有优异的传感性能，能够更好的满足植入式传感器的需求。图7说明了所制备的智能传感式水凝胶人工椎间盘在不同压应力下具有优异的传感性能，能够更好的满足植入式传感器的需求。如图8所示，在长循环的传感性能测试下，传感式水凝胶人工椎间盘能保持稳定的传感信号，为其在体内的长期信号传感工作奠定了基础。Figure 4 illustrates that the prepared sensing hydrogel artificial intervertebral disc has high compressive strength and elastic modulus. Figure 5 illustrates that under multiple cycles of compression, the sensing hydrogel artificial intervertebral disc has good compressive stability and is expected to replace the body's natural intervertebral disc, cartilage and other load-bearing tissues. Figure 6 illustrates that the prepared intelligent sensing hydrogel artificial intervertebral disc has excellent sensing performance under different compressive strains, which can better meet the needs of implantable sensors. Figure 7 illustrates that the prepared intelligent sensing hydrogel artificial intervertebral disc has excellent sensing performance under different compressive stresses, which can better meet the needs of implantable sensors. As shown in Figure 8, under the long-cycle sensing performance test, the sensing hydrogel artificial intervertebral disc can maintain a stable sensing signal, laying the foundation for its long-term signal sensing work in the body.
实施例4Example 4
本实施例提供了一种传感式水凝胶人工椎间盘的制备方法，其包括如下步骤：This embodiment provides a method for preparing a sensing hydrogel artificial intervertebral disc, which comprises the following steps:
(1)配制30ml聚乙烯醇(PVA)溶液，聚乙烯醇的质量分数为20wt％，搅拌至完全溶解。(1) Prepare 30 ml of polyvinyl alcohol (PVA) solution with a mass fraction of 20 wt % and stir until it is completely dissolved.
(2)将聚乙烯醇溶液倒入椎间盘型的硅胶模具中，置于低温环境(-15℃)中冷冻并在室温下解冻，进行冻融循环4次；(2) Pour the polyvinyl alcohol solution into a disc-shaped silicone mold, freeze it in a low-temperature environment (-15°C), and thaw it at room temperature, performing freeze-thaw cycles four times;
(3)将冻融后得到的圆柱形水凝胶在侧面和表面中间区域涂覆聚二甲基硅氧烷，控制厚度在800μm，中间区域涂覆的直径约为2cm，放入烘箱中，温度设置40℃，干燥12h；(3) The cylindrical hydrogel obtained after freezing and thawing was coated with polydimethylsiloxane on the side and the middle area of the surface, with a thickness of 800 μm and a diameter of about 2 cm in the middle area, and placed in an oven at 40°C for drying for 12 h;
(4)剥离干燥后水凝胶表面的聚二甲基硅氧烷，在浓度为1M的柠檬酸钠(CA)溶液中浸泡24h进行再水合，进一步提高水凝胶的强度；(4) stripping the polydimethylsiloxane on the surface of the hydrogel after drying and soaking it in a 1 M sodium citrate (CA) solution for 24 h for rehydration to further improve the strength of the hydrogel;
(5)将水合盐析后的水凝胶在去离子水中浸泡12h，以达到平衡，得到抗压且保持区域各向异性的水凝胶，最终制备出传感式水凝胶人工椎间盘。(5) The hydrated and salted-out hydrogel was immersed in deionized water for 12 h to achieve equilibrium, thereby obtaining a hydrogel that is compressive-resistant and maintains regional anisotropy, and finally preparing a sensing hydrogel artificial intervertebral disc.
(6)在传感式水凝胶人工椎间盘的上下表面固定铜线作为电极，与外部数字万用表连接，数字万用表将传感式水凝胶人工椎间盘的电阻变化实时传输到手机终端。(6) Copper wires are fixed on the upper and lower surfaces of the sensing hydrogel artificial intervertebral disc as electrodes and connected to an external digital multimeter. The digital multimeter transmits the resistance change of the sensing hydrogel artificial intervertebral disc to a mobile phone terminal in real time.
以尺寸为长径4.5cm，短径3.5cm的传感式水凝胶人工椎间盘为例：Take the sensor-type hydrogel artificial intervertebral disc with a long diameter of 4.5 cm and a short diameter of 3.5 cm as an example:
如图9所示，将商用脊柱模型中原有的椎间盘取出，将传感式水凝胶人工椎间盘植入到模型中，取代的原有的椎间盘部位，将脊柱模型模拟前后屈伸，测试其传感性能，说明了脊柱在不同的活动状态时，传感式水凝胶人工椎间盘具有不同的压缩程度，进而获得了不同的电阻变化，实现了对椎间盘受力状态的监测。As shown in Figure 9, the original intervertebral disc in the commercial spine model was removed, and a sensing hydrogel artificial intervertebral disc was implanted into the model to replace the original intervertebral disc. The spine model was simulated to flex and extend forward and backward to test its sensing performance. It was shown that when the spine is in different activity states, the sensing hydrogel artificial intervertebral disc has different compression degrees, and thus different resistance changes are obtained, thereby realizing the monitoring of the stress state of the intervertebral disc.
上述实施例提供的传感式水凝胶人工椎间盘制备工艺简单、机械性能以及传感性能优良，植入动物体内可以替代动物天然的椎间盘组织，起到承重的作用，同时可以通过传感性能直接反馈椎间盘的受力和恢复状态，有利于为实施椎间盘置换术后康复阶段的患者制定个性化康复方案。The sensing hydrogel artificial intervertebral disc provided in the above-mentioned embodiment has a simple preparation process, excellent mechanical properties and sensing properties, and can be implanted in animals to replace the natural intervertebral disc tissue of the animals and play a load-bearing role. At the same time, the sensing performance can directly feedback the stress and recovery state of the intervertebral disc, which is conducive to formulating personalized rehabilitation plans for patients in the rehabilitation stage after intervertebral disc replacement surgery.
在另一些实施例中，还提供了一种传感式水凝胶人工椎间盘，其采用如上述所述的传感式水凝胶人工椎间盘的制备方法中的步骤制备而成；In other embodiments, a sensing hydrogel artificial intervertebral disc is provided, which is prepared by the steps in the method for preparing the sensing hydrogel artificial intervertebral disc as described above;
所述传感式水凝胶人工椎间盘由纤维环部位及髓核部位构成的一体化水凝胶结构；The sensing hydrogel artificial intervertebral disc is an integrated hydrogel structure consisting of an annulus fibrosus part and a nucleus pulposus part;
所述传感式水凝胶人工椎间盘的表面设置有电极，所述电极与监控终端相连。Electrodes are arranged on the surface of the sensing hydrogel artificial intervertebral disc, and the electrodes are connected to a monitoring terminal.
其中，在制备出一种传感式水凝胶人工椎间盘后，在其上下表面固定铜线作为电极传输电信号输出，例如与数字万用表连接，将电信号无线传输到监控终端。Among them, after a sensing hydrogel artificial intervertebral disc is prepared, copper wires are fixed on its upper and lower surfaces as electrodes to transmit electrical signal output, for example, connected to a digital multimeter to wirelessly transmit the electrical signal to a monitoring terminal.
此处需要说明的是，电极连接方式包括但不限于单个位置，多个位置以及阵列式传感输出。本领域技术人员通过电极设计达到多向传感监测。It should be noted that the electrode connection modes include but are not limited to single position, multiple positions and array sensing output. Those skilled in the art can achieve multi-directional sensing monitoring through electrode design.
在一个或多个实施例中，所述传感式水凝胶人工椎间盘的表面还包覆/涂覆有防粘连层，这样形成防粘连的人工椎间盘。In one or more embodiments, the surface of the sensing hydrogel artificial intervertebral disc is further coated with an anti-adhesion layer, thus forming an anti-adhesion artificial intervertebral disc.
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410054665.4ACN117883633B (en) | 2024-01-12 | 2024-01-12 | Sensing hydrogel artificial intervertebral disc and preparation method thereof |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410054665.4ACN117883633B (en) | 2024-01-12 | 2024-01-12 | Sensing hydrogel artificial intervertebral disc and preparation method thereof |
| Publication Number | Publication Date |
|---|---|
| CN117883633A CN117883633A (en) | 2024-04-16 |
| CN117883633Btrue CN117883633B (en) | 2024-09-10 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410054665.4AActiveCN117883633B (en) | 2024-01-12 | 2024-01-12 | Sensing hydrogel artificial intervertebral disc and preparation method thereof |
| Country | Link |
|---|---|
| CN (1) | CN117883633B (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0700671B1 (en)* | 1994-09-08 | 2001-08-08 | Stryker Technologies Corporation | Hydrogel intervertebral disc nucleus |
| US7169405B2 (en)* | 2003-08-06 | 2007-01-30 | Warsaw Orthopedic, Inc. | Methods and devices for the treatment of intervertebral discs |
| US8591950B2 (en)* | 2010-05-27 | 2013-11-26 | Covidien Lp | Hydrogel implants with varying degrees of crosslinking |
| Publication number | Publication date |
|---|---|
| CN117883633A (en) | 2024-04-16 |
| Publication | Publication Date | Title |
|---|---|---|
| EP3490624B1 (en) | Nerve guidance conduits, methods of production and uses thereof | |
| Yin et al. | Double network hydrogels: Design, fabrication, and application in biomedicines and foods | |
| Goh et al. | Alginates as a useful natural polymer for microencapsulation and therapeutic applications | |
| US10064736B2 (en) | Engineered intervertebral disc (IVD) for degenerated disc disease | |
| CN113174080B (en) | Biological glass nanofiber porous scaffold and preparation and application thereof | |
| US20070141108A1 (en) | Fiber-reinforced water-swellable articles | |
| Gloria et al. | Dynamic-mechanical properties of a novel composite intervertebral disc prosthesis | |
| CN106075597B (en) | Biomimetic tissue and its preparation based on bladder acellular matrix-cell-three-dimensional fiber network | |
| WO2002076336A2 (en) | Implantable prosthetic or tissue expanding device | |
| CN101820930A (en) | Biomaterial scaffolds for controlled tissue growth | |
| CN114149598B (en) | Composite intelligent hydrogel with diabetes mellitus microenvironment responsiveness as well as preparation method and application thereof | |
| CN114618021B (en) | Intelligent bionic tendon scaffold and preparation method thereof | |
| CN105944143A (en) | Bionic tissue based on acellular matrix-cell-three-dimensional fiber network and preparation method of bionic tissue | |
| CN117883633B (en) | Sensing hydrogel artificial intervertebral disc and preparation method thereof | |
| CN108525003A (en) | Based on the double cross of acylhydrazone key and hydrophobe self assembly connection hybridized hydrogel, preparation method and skin histology wound repair agent | |
| CN117164891A (en) | Method for preparing tough hydrogel based on directional annealing casting method and application of method | |
| CN115887742A (en) | Preparation method of antibacterial functional collagen-based injectable self-healing hydrogel | |
| Wu et al. | Thermo-responsive microneedles patch for transdermal drug delivery via squeezing in diabetic foot ulcers | |
| CN106492278A (en) | A kind of artificial skin and preparation method thereof | |
| CN110732038B (en) | Silk fibroin fiber hollow nerve conduit and preparation method and application thereof | |
| Yao et al. | Channel structure design and biological properties of silk fibroin/sericin sponge nerve scaffolds | |
| Subramanian et al. | Hydrogels: Classification, synthesis, characterization, and applications | |
| Liang et al. | Biomimetic Versatile Anisotropic, Electroactive Cellulose Hydrogel Scaffolds Tailored from Fern Stem Serving as Nerve Conduit and Cardiac Patch | |
| CN116284861B (en) | Conductive hydrogel, gel ball and preparation method and application thereof | |
| CN115894709B (en) | Recombinant human elastin with skin damage repairing effect and application thereof |
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |