技术领域Technical field
本发明属于生物医用材料技术领域，具体涉及一种腹壁缺损修复材料的制备方法。The invention belongs to the technical field of biomedical materials, and specifically relates to a method for preparing abdominal wall defect repair materials.
背景技术Background technique
腹壁、胸壁、硬脑膜的内部软组织缺损常由手术创伤、原发性或继发性肿瘤切除、创伤性损伤、软组织感染等引起，全世界每年至少有40万例手术和超过100亿美元的医疗费用。近年来，由于手术挑战和不理想的治疗结果，破坏浆膜和肌肉层的内部软组织缺损的修复引起了极大的关注。肌层破坏难以缝合，浆膜损伤可引起明显的脏器粘连。在过去的几十年中，无张力修复手术被推荐为腹壁缺损等软组织缺损的标准治疗方法，其中不同类型的补片被广泛使用。Internal soft tissue defects of the abdominal wall, chest wall, and dura mater are often caused by surgical trauma, primary or secondary tumor resection, traumatic injury, soft tissue infection, etc. There are at least 400,000 surgeries and more than 10 billion US dollars in medical treatment worldwide every year. cost. In recent years, the repair of internal soft tissue defects disrupting the serosa and muscle layers has attracted significant attention due to surgical challenges and suboptimal treatment outcomes. Damage to the muscle layer is difficult to suture, and damage to the serosa can cause obvious organ adhesions. Over the past few decades, tension-free repair surgery has been recommended as the standard treatment for soft tissue defects such as abdominal wall defects, in which different types of mesh are widely used.
传统合成补片（例如，聚丙烯（PP）形的和聚酯网片）具有高强度、轻重量和抗变形等优点，已广泛用于软组织缺损的无张力修复。但是，由于明显的异物反应，这些补片可能导致严重的内脏粘连和不良的伤口愈合，这可能是由于它缺乏用于细胞迁移和生长的微结构。Traditional synthetic patches (e.g., polypropylene (PP)-shaped and polyester mesh) have the advantages of high strength, light weight, and resistance to deformation, and have been widely used for tension-free repair of soft tissue defects. However, due to significant foreign body reaction, these patches can cause severe visceral adhesions and poor wound healing, possibly due to its lack of microstructure for cell migration and growth.
发明内容Contents of the invention
为了匹配所修复腹壁的力学强度，以及防止粘连现象的产生，本发明通过受腹膜启发，提供一种腹壁缺损修复材料的制备方法，实现材料和修复部位的力学匹配，以及修复过程中抗粘连问题的解决，同时还辅以良好的抗金黄色葡萄球菌的性能，能有效减少术中感染的风险。In order to match the mechanical strength of the repaired abdominal wall and prevent the occurrence of adhesions, the present invention provides a preparation method of abdominal wall defect repair materials inspired by the peritoneum, achieving mechanical matching between the material and the repair site and anti-adhesive problems during the repair process. It is also supplemented by good anti-Staphylococcus aureus properties, which can effectively reduce the risk of intraoperative infection.
本发明采用如下技术方案：The present invention adopts the following technical solutions:
一种腹壁缺损修复材料的制备方法，采用Solidworks构建复合材料内层支架模型，通过将3D打印的海藻酸钠（SA）/聚乙烯醇（PVA）/壳聚糖季铵盐（HACC）内层支架与膜造法及盐析法制备的PVA外层支架复合制备，形成不对称结构的腹壁修复材料。A method of preparing abdominal wall defect repair materials, using Solidworks to build a composite inner scaffold model, by 3D printing the inner layer of sodium alginate (SA)/polyvinyl alcohol (PVA)/chitosan quaternary ammonium salt (HACC) The stent is compositely prepared with a PVA outer stent prepared by membrane manufacturing method and salting-out method to form an asymmetrically structured abdominal wall repair material.
具体包括如下步骤：Specifically, it includes the following steps:
第一步，膜造法结合盐析法制备外层修复材料：In the first step, the membrane manufacturing method combined with the salting out method is used to prepare the outer layer repair material:
（1）将14.4g聚乙烯醇倒入三颈烧瓶，加入80ml去离子水，温度设置为90℃，速度设置为400r/min，持续搅拌两个小时，获得粘稠的透明的聚乙烯醇液体；(1) Pour 14.4g of polyvinyl alcohol into a three-necked flask, add 80ml of deionized water, set the temperature to 90°C, and the speed to 400r/min. Continue stirring for two hours to obtain a viscous and transparent polyvinyl alcohol liquid. ;
（2）将聚乙烯醇液体置于磁力超声清洗机中超声10分钟，去除其中的气泡，获得液态膜造法前体；(2) Place the polyvinyl alcohol liquid in a magnetic ultrasonic cleaning machine and ultrasonicate for 10 minutes to remove air bubbles and obtain a liquid membrane precursor;
（3）将膜造法前体置于10ml注射器中，缓慢注射入模具内；(3) Place the membrane-making precursor into a 10ml syringe and slowly inject it into the mold;
（4）对材料进行三次冻融循环：-20℃下冷冻12h，-4℃下解冻12h；(4) Perform three freeze-thaw cycles on the material: freeze at -20°C for 12 hours, and thaw at -4°C for 12 hours;
（5）制备一系列浓度梯度的硫酸钠溶液：0.1、0.3、0.5、0.7、0.9mol/L，各20ml；(5) Prepare a series of concentration gradient sodium sulfate solutions: 0.1, 0.3, 0.5, 0.7, 0.9mol/L, 20ml each;
（6）对模具冻融好的聚乙烯醇膜片进行盐析处理，将其浸泡在不同浓度的硫酸钠溶液中24h，去离子水中12h；(6) Perform salting-out treatment on the frozen-thawed polyvinyl alcohol membrane of the mold, and soak it in sodium sulfate solutions of different concentrations for 24 hours and deionized water for 12 hours;
第二步，3D打印法制备水凝胶支架：The second step is to prepare the hydrogel scaffold using 3D printing:
将3D打印生物墨水置于5ml的注射器中，连接打印针头，在环境温度为25℃、湿度40%、针头温度37℃、机床温度10℃、打印速度6mm/s、挤出速度7mm/s、回抽0.25mm、抬高0.2mm、尺寸10*10/15*15mm、线间距1.2mm、层高0.2mm、支架高度0.4mm的条件下，打印时间持续3min，获得水凝胶支架，使用4wt%氯化钙溶液化学交联之后，将水凝胶支架于 -20℃下冷冻12h，-4℃解冻12h，进行反复冻融物理交联三次；Place the 3D printing bio-ink into a 5ml syringe, connect the printing needle, and set the environment temperature to 25°C, humidity 40%, needle temperature 37°C, machine tool temperature 10°C, printing speed 6mm/s, and extrusion speed 7mm/s. Under the conditions of retraction 0.25mm, elevation 0.2mm, size 10*10/15*15mm, line spacing 1.2mm, layer height 0.2mm, and scaffold height 0.4mm, the printing time lasts 3 minutes to obtain the hydrogel scaffold, using 4wt After chemical cross-linking with % calcium chloride solution, the hydrogel scaffold was frozen at -20°C for 12 hours, thawed at -4°C for 12 hours, and physically cross-linked by repeated freezing and thawing three times;
第三步，将膜造法结合盐析法制备的外层膜与3D打印水凝胶支架，用0 .5ml~1ml的3D打印生物墨水进行粘合，最终获得一种腹壁缺损修复材料。In the third step, the outer membrane prepared by the membrane manufacturing method combined with the salting-out method and the 3D printed hydrogel scaffold are bonded with 0.5ml~1ml of 3D printed bioink to finally obtain an abdominal wall defect repair material.
膜造法结合盐析法所制备的外层，成膜后其表面为致密结构，水接触角为20°，含水率为60%（盐析浓度为0.7mol/L）。The outer layer prepared by the membrane manufacturing method combined with the salting-out method has a dense structure on the surface after the film is formed, with a water contact angle of 20° and a moisture content of 60% (salting-out concentration is 0.7mol/L).
所述3D打印生物墨水的制备方法如下：The preparation method of the 3D printing bioink is as follows:
（1）称取质量比为5：6：1的海藻酸钠、聚乙烯醇和壳聚糖季铵盐粉末备用；(1) Weigh sodium alginate, polyvinyl alcohol and chitosan quaternary ammonium salt powder with a mass ratio of 5:6:1 for later use;
（2）将聚乙烯醇在90℃下、转速为600r/min的磁力搅拌锅中，持续搅拌2h；(2) Stir polyvinyl alcohol in a magnetic stirring pot at 90°C and 600r/min for 2 hours;
（3）然后冷却至室温，加入海藻酸钠粉末，室温条件下机械搅拌30min，转速400r/min，直至海藻酸钠粉末完全溶解；(3) Then cool to room temperature, add sodium alginate powder, and stir mechanically at room temperature for 30 minutes at a speed of 400r/min until the sodium alginate powder is completely dissolved;
（4）将0 .2g壳聚糖季铵盐粉末缓慢加入溶解好的溶液中，相同条件下继续搅拌30min，即制得3D打印生物墨水。(4) Slowly add 0.2g chitosan quaternary ammonium salt powder into the dissolved solution, and continue stirring for 30 minutes under the same conditions to prepare 3D printing bioink.
本发明的有益效果如下：The beneficial effects of the present invention are as follows:
本发明采用膜造法结合盐析法以及3D打印技术制备的一种具有不对称结构的腹壁缺损修复材料。纯聚乙烯醇通过膜造法进行冻融交联，盐析法改进力学性能后，能够很好地匹配腹壁的力学性能，同时，可以复制腹膜的致密性以达到抗粘连的效果，修复材料的外层主要起到保护和支撑作用，提供必要的力学强度，同时可以在修复过程中防止软组织的长入，形成软组织粘连。对于腹壁修复来说可以减轻患者对于肠梗阻等并发症的困扰。多孔内层(3D打印水凝胶)由5wt%海藻酸钠、6wt%聚乙烯醇(PVA)和1wt%壳聚糖季铵盐(HACC)所制备。内层主要起到抗菌的作用,其多孔结构为细胞的迁移提供了合适的结构和微环境。最终获得一种受损腹壁修复的材料。The present invention adopts a membrane-making method combined with a salting-out method and 3D printing technology to prepare an abdominal wall defect repair material with an asymmetric structure. Pure polyvinyl alcohol is freeze-thaw cross-linked through the membrane-making method. After the mechanical properties are improved by the salting-out method, it can well match the mechanical properties of the abdominal wall. At the same time, it can replicate the denseness of the peritoneum to achieve the anti-adhesion effect, and the repair material is more durable. The outer layer mainly plays a protective and supporting role, providing necessary mechanical strength, and at the same time, it can prevent the ingrowth of soft tissue and the formation of soft tissue adhesion during the repair process. Abdominal wall repair can reduce patients’ worries about complications such as intestinal obstruction. The porous inner layer (3D printed hydrogel) was prepared from 5wt% sodium alginate, 6wt% polyvinyl alcohol (PVA) and 1wt% chitosan quaternary ammonium salt (HACC). The inner layer mainly plays an antibacterial role, and its porous structure provides a suitable structure and microenvironment for cell migration. Finally, a material for damaged abdominal wall repair was obtained.
本发明具有出色的生物相容性、低毒性和低免疫原性。在腹壁损伤处，外层可有效防止粘连，避免其它并发症的产生，内层能有效控制感染的同时促进皮肤再生，同时它还有利于细胞的黏附和生长，从而提高创面愈合的质量和速率。The invention has excellent biocompatibility, low toxicity and low immunogenicity. At abdominal wall injuries, the outer layer can effectively prevent adhesions and avoid other complications. The inner layer can effectively control infection while promoting skin regeneration. It is also conducive to cell adhesion and growth, thereby improving the quality and rate of wound healing. .
附图说明Description of the drawings
图1为实例1~6，所制备的外层腹壁缺损修复材料的宏观图。Figure 1 is a macro view of the outer abdominal wall defect repair material prepared in Examples 1 to 6.
图2为实例1~6，所制备的外层腹壁缺损修复材料的微观图。Figure 2 is a microscopic view of the outer abdominal wall defect repair material prepared in Examples 1 to 6.
图3为实例1~6，所制备的外层腹壁缺损修复材料的拉伸应力应变图。Figure 3 is a tensile stress strain diagram of the outer abdominal wall defect repair material prepared in Examples 1 to 6.
图4为实例1~6，所制备的外层腹壁缺损修复材料的缝合拉伸应力应变图。Figure 4 is a suture tensile stress strain diagram of the outer abdominal wall defect repair material prepared in Examples 1 to 6.
图5为实例1~6，所制备的外层腹壁缺损修复材料的细胞抗粘附图。Figure 5 is a graph of cell anti-adhesion of the outer abdominal wall defect repair material prepared in Examples 1 to 6.
图6为实例1~6，所制备的内层水凝胶支架材料的抗菌图。Figure 6 is the antibacterial pattern of the inner hydrogel scaffold material prepared in Examples 1 to 6.
图7为实例1~6，所制备的内层水凝胶支架材料的血液相容性图。Figure 7 is a blood compatibility diagram of the inner hydrogel scaffold material prepared in Examples 1 to 6.
图8为实例1和实例5，所制备的腹壁缺损修复材料的CCK-8图。Figure 8 is a CCK-8 diagram of the abdominal wall defect repair materials prepared in Example 1 and Example 5.
具体实施方式Detailed ways
下面通过实施例来进一步说明本发明，但不局限于以下实施例。The present invention is further described below through examples, but is not limited to the following examples.
实施例1Example 1
3D打印法制备内层水凝胶支架：将1.2g聚乙烯醇(PVA)溶入20ml去离子水，盖上锡纸（减少去离子水挥发），调节温度为90℃、转速为400r/min，持续搅拌2h，直至聚乙烯醇(PVA)完全溶解；待聚乙烯醇(PVA)溶液自然冷却至室温（25℃），将1g海藻酸钠(SA)缓慢加入溶解好的聚乙烯醇（PVA）溶液中，机械搅拌30min，转速400r/min，直至海藻酸钠(SA)完全溶解；加入0.2g壳聚糖季铵盐(HACC)粉末，机械搅拌30min，转速400r/min，即制得3D打印水凝胶。将获得溶胶状3D打印水凝胶置于注射器（BD-5ml）中，连接打印针头（0.25G），在环境温度为25℃、湿度40%、针头温度37℃、机床温度10℃、打印速度6mm/s、挤出速度7mm/s、回抽（S.K）0.25mm、抬高(H.P)0.2mm、尺寸10*10mm、线间距1.2mm、层高0.2mm、支架高度0.4mm的条件下，打印时间持续5min，获得海藻酸钠(SA)、聚乙烯醇(PVA)和壳聚糖季铵盐(HACC)复合3D打印水凝胶支架，使用4wt%氯化钙溶液对海藻酸钠(SA)交联，将支架于-20℃下冷冻12h，-4℃解冻12h，对聚乙烯醇（PVA）进行三次循环冻融物理交联后，获得内层水凝胶支架。Prepare the inner hydrogel scaffold by 3D printing method: Dissolve 1.2g polyvinyl alcohol (PVA) into 20ml deionized water, cover with tin foil (to reduce the evaporation of deionized water), adjust the temperature to 90°C and the rotation speed to 400r/min. Continue stirring for 2 hours until the polyvinyl alcohol (PVA) is completely dissolved; when the polyvinyl alcohol (PVA) solution naturally cools to room temperature (25°C), slowly add 1g of sodium alginate (SA) to the dissolved polyvinyl alcohol (PVA). In the solution, stir mechanically for 30 minutes at a speed of 400r/min until sodium alginate (SA) is completely dissolved; add 0.2g of chitosan quaternary ammonium salt (HACC) powder, stir mechanically for 30min at a speed of 400r/min, and 3D printing is obtained Hydrogels. Place the obtained sol-like 3D printing hydrogel into a syringe (BD-5ml), connect the printing needle (0.25G), and set the environment temperature to 25°C, humidity 40%, needle temperature 37°C, machine tool temperature 10°C, and printing speed. 6mm/s, extrusion speed 7mm/s, retraction (S.K) 0.25mm, elevation (H.P) 0.2mm, size 10*10mm, line spacing 1.2mm, layer height 0.2mm, bracket height 0.4mm, The printing time lasted for 5 minutes, and a composite 3D printed hydrogel scaffold of sodium alginate (SA), polyvinyl alcohol (PVA) and chitosan quaternary ammonium salt (HACC) was obtained. 4wt% calcium chloride solution was used to test sodium alginate (SA). ) cross-linking, the scaffold was frozen at -20°C for 12 hours, and thawed at -4°C for 12 hours. After three cycles of freeze-thaw physical cross-linking of polyvinyl alcohol (PVA), the inner hydrogel scaffold was obtained.
外层腹壁缺损修复材料的制备：将14.4g聚乙烯醇（PVA）溶入80ml去离子水中，温度为90℃，时间为2h，得到聚乙烯醇(PVA)溶液，磁力超声清洗机中超声10min，去除气泡，使用10ml注射器将聚乙烯醇(PVA)溶液均匀注射到定制模具中，-20℃下冷冻12h，-4℃下解冻12h，经过三次循环以后，获得外层腹壁缺损修复材料。Preparation of outer abdominal wall defect repair material: Dissolve 14.4g polyvinyl alcohol (PVA) into 80ml deionized water at a temperature of 90°C for 2 hours to obtain a polyvinyl alcohol (PVA) solution, and ultrasonicate in a magnetic ultrasonic cleaning machine for 10 minutes , remove air bubbles, use a 10ml syringe to evenly inject polyvinyl alcohol (PVA) solution into the custom mold, freeze at -20°C for 12h, and thaw at -4°C for 12h. After three cycles, the outer abdominal wall defect repair material is obtained.
实施例2Example 2
3D打印法制备内层水凝胶支架同实例1。The inner hydrogel scaffold prepared by 3D printing method is the same as Example 1.
外层腹壁缺损修复材料的制备：将14.4g聚乙烯醇（PVA）溶入80ml去离子水中，温度为90℃，时间为2h，得到聚乙烯醇(PVA)溶液，磁力超声清洗机中超声10min，去除气泡，使用10ml注射器将聚乙烯醇(PVA)溶液均匀注射到定制模具中，-20℃下冷冻12h，-4℃下解冻12h，经过三次循环以后，在0.1wt%硫酸钠(Na2SO4)溶液中浸泡24h，在去离子水中浸泡12h，获得外层腹壁缺损修复材料。Preparation of outer abdominal wall defect repair material: Dissolve 14.4g polyvinyl alcohol (PVA) into 80ml deionized water at a temperature of 90°C for 2 hours to obtain a polyvinyl alcohol (PVA) solution, and ultrasonicate in a magnetic ultrasonic cleaning machine for 10 minutes , remove the bubbles, use a 10ml syringe to evenly inject the polyvinyl alcohol (PVA) solution into the custom mold, freeze at -20°C for 12h, and thaw at -4°C for 12h. After three cycles, inject the polyvinyl alcohol (PVA) solution into the custom mold with 0.1wt% sodium sulfate (Na2 Soak in SO4 ) solution for 24 hours and deionized water for 12 hours to obtain outer abdominal wall defect repair material.
实施例3Example 3
3D打印法制备内层水凝胶支架同实例1。The inner hydrogel scaffold prepared by 3D printing method is the same as Example 1.
外层腹壁缺损修复材料的制备：将14.4g聚乙烯醇（PVA）溶入80ml去离子水中，温度为90℃，时间为2h，得到聚乙烯醇(PVA)溶液，磁力超声清洗机中超声10min，去除气泡，使用10ml注射器将聚乙烯醇(PVA)溶液均匀注射到定制模具中，-20℃下冷冻12h，-4℃下解冻12h，经过三次循环以后，在0.3wt%硫酸钠(Na2SO4)溶液中浸泡24h，在去离子水中浸泡12h，获得外层腹壁缺损修复材料。Preparation of outer abdominal wall defect repair material: Dissolve 14.4g polyvinyl alcohol (PVA) into 80ml deionized water at a temperature of 90°C for 2 hours to obtain a polyvinyl alcohol (PVA) solution, and ultrasonicate in a magnetic ultrasonic cleaning machine for 10 minutes , remove the bubbles, use a 10ml syringe to evenly inject the polyvinyl alcohol (PVA) solution into the custom mold, freeze at -20°C for 12h, and thaw at -4°C for 12h. After three cycles, inject the solution into the custom mold with 0.3wt% sodium sulfate (Na2 Soak in SO4 ) solution for 24 hours and deionized water for 12 hours to obtain outer abdominal wall defect repair material.
实施例4Example 4
3D打印法制备内层水凝胶支架同实例1。The inner hydrogel scaffold prepared by 3D printing method is the same as Example 1.
外层腹壁缺损修复材料的制备：将14.4g聚乙烯醇（PVA）溶入80ml去离子水中，温度为90℃，时间为2h，得到聚乙烯醇(PVA)溶液，磁力超声清洗机中超声10min，去除气泡，使用10ml注射器将聚乙烯醇(PVA)溶液均匀注射到定制模具中，-20℃下冷冻12h，-4℃下解冻12h，经过三次循环以后，在0.5wt%硫酸钠(Na2SO4)溶液中浸泡24h，在去离子水中浸泡12h，获得外层腹壁缺损修复材料。Preparation of outer abdominal wall defect repair material: Dissolve 14.4g polyvinyl alcohol (PVA) into 80ml deionized water at a temperature of 90°C for 2 hours to obtain a polyvinyl alcohol (PVA) solution, and ultrasonicate in a magnetic ultrasonic cleaning machine for 10 minutes , remove the bubbles, use a 10ml syringe to evenly inject the polyvinyl alcohol (PVA) solution into the custom mold, freeze at -20°C for 12h, and thaw at -4°C for 12h. After three cycles, inject the solution into the custom mold with 0.5wt% sodium sulfate (Na2 Soak in SO4 ) solution for 24 hours and deionized water for 12 hours to obtain outer abdominal wall defect repair material.
实施例5Example 5
3D打印法制备内层水凝胶支架同实例1。The inner hydrogel scaffold prepared by 3D printing method is the same as Example 1.
外层腹壁缺损修复材料的制备：将14.4g聚乙烯醇（PVA）溶入80ml去离子水中，温度为90℃，时间为2h，得到聚乙烯醇(PVA)溶液，磁力超声清洗机中超声10min，去除气泡，使用10ml注射器将聚乙烯醇(PVA)溶液均匀注射到定制模具中，-20℃下冷冻12h，-4℃下解冻12h，经过三次循环以后，在0.7wt%硫酸钠(Na2SO4)溶液中浸泡24h，在去离子水中浸泡12h，获得外层腹壁缺损修复材料。Preparation of outer abdominal wall defect repair material: Dissolve 14.4g polyvinyl alcohol (PVA) into 80ml deionized water at a temperature of 90°C for 2 hours to obtain a polyvinyl alcohol (PVA) solution, and ultrasonicate in a magnetic ultrasonic cleaning machine for 10 minutes , remove the bubbles, use a 10ml syringe to evenly inject the polyvinyl alcohol (PVA) solution into the custom mold, freeze at -20°C for 12h, and thaw at -4°C for 12h. After three cycles, inject the solution into the custom mold with 0.7wt% sodium sulfate (Na2 Soak in SO4 ) solution for 24 hours and deionized water for 12 hours to obtain outer abdominal wall defect repair material.
实施例6Example 6
3D打印法制备内层水凝胶支架同实例1。The inner hydrogel scaffold prepared by 3D printing method is the same as Example 1.
外层腹壁缺损修复材料的制备：将14.4g聚乙烯醇（PVA）溶入80ml去离子水中，温度为90℃，时间为2h，得到聚乙烯醇(PVA)溶液，磁力超声清洗机中超声10min，去除气泡，使用10ml注射器将聚乙烯醇(PVA)溶液均匀注射到定制模具中，-20℃下冷冻12h，-4℃下解冻12h，经过三次循环以后，在0.9wt%硫酸钠(Na2SO4)溶液中浸泡24h，在去离子水中浸泡12h，获得外层腹壁缺损修复材料。Preparation of outer abdominal wall defect repair material: Dissolve 14.4g polyvinyl alcohol (PVA) into 80ml deionized water at a temperature of 90°C for 2 hours to obtain a polyvinyl alcohol (PVA) solution, and ultrasonicate in a magnetic ultrasonic cleaning machine for 10 minutes , remove air bubbles, use a 10ml syringe to evenly inject the polyvinyl alcohol (PVA) solution into the custom mold, freeze at -20°C for 12h, and thaw at -4°C for 12h. After three cycles, inject the solution into the custom mold with 0.9wt% sodium sulfate (Na2 Soak in SO4 ) solution for 24 hours and deionized water for 12 hours to obtain outer abdominal wall defect repair material.
以上方法制得的腹壁缺损修复材料应用于人体不会产生免疫排斥和过敏反应。采用仿生的思路，结合膜造法和盐析法，制备出力学性能优异，抗粘附性能良好的外层材料。使用3D打印的方法制备内层支架，具有促进细胞生长、迁移的细胞外基质结构，其有良好的生物相容性。在软组织缺损修复领域中，具有广阔的临床应用前景。The abdominal wall defect repair material prepared by the above method will not produce immune rejection and allergic reactions when applied to the human body. Using bionic ideas, combined with membrane manufacturing method and salting-out method, an outer layer material with excellent mechanical properties and good anti-adhesion properties is prepared. The inner scaffold is prepared using 3D printing method, which has an extracellular matrix structure that promotes cell growth and migration, and has good biocompatibility. It has broad clinical application prospects in the field of soft tissue defect repair.
图1为不同浓度硫酸钠溶液处理膜造法制备的外层膜（从左至右依次为实施例1-实施例6），可以看出盐析法可以明显影响聚乙烯醇分子的结晶度，随着硫酸钠浓度越高，外层膜的不透明性越高，结晶度越高。Figure 1 shows the outer membranes prepared by membrane manufacturing methods treated with sodium sulfate solutions of different concentrations (from left to right, Example 1 to Example 6). It can be seen that the salting out method can significantly affect the crystallinity of polyvinyl alcohol molecules. As the sodium sulfate concentration increases, the outer film becomes more opaque and crystalline.
图2为实例1~6的SEM图（a至f依次为实施例1-6），可以看出随着硫酸钠浓度越高，分子量小的聚乙烯醇分子链从材料里面排出，导致材料表面出现较小的孔隙，但材料表面整体呈致密的状态。Figure 2 is the SEM image of Examples 1 to 6 (a to f are Examples 1 to 6 in order). It can be seen that as the concentration of sodium sulfate increases, the polyvinyl alcohol molecular chains with small molecular weight are discharged from the material, resulting in the surface of the material Small pores appear, but the overall surface of the material is dense.
图3为实例1~6的应力应变图，可以看出随着硫酸钠浓度越高，材料的力学性能逐渐提高。实例1~6的拉伸强度分别为：0.15MPa、1.21 MPa、2.95 MPa、5.58 MPa、5.91 MPa、6.57 MPa，比较贴合人体腹壁的力学参数。Figure 3 is the stress strain diagram of Examples 1 to 6. It can be seen that as the concentration of sodium sulfate increases, the mechanical properties of the material gradually increase. The tensile strengths of Examples 1 to 6 are respectively: 0.15MPa, 1.21 MPa, 2.95 MPa, 5.58 MPa, 5.91 MPa, and 6.57 MPa, which are relatively consistent with the mechanical parameters of the human abdominal wall.
图4为实例1~6的缝合拉伸应力应变图，同样是随着硫酸钠浓度越高，材料的力学性能逐渐提高。缝合拉伸强度分别为：0.15 MPa、0.12 MPa、0.27 MPa、2.95 MPa、1.05 MPa、1.45 MPa，即使是最低缝合拉伸强度的材料也能够在缝合植入人体后，很好地承受最高0.02MPa的腹压。Figure 4 shows the suture tensile stress and strain diagrams of Examples 1 to 6. Likewise, as the concentration of sodium sulfate increases, the mechanical properties of the material gradually increase. The suture tensile strengths are: 0.15 MPa, 0.12 MPa, 0.27 MPa, 2.95 MPa, 1.05 MPa, 1.45 MPa. Even the material with the lowest suture tensile strength can withstand up to 0.02MPa well after being sutured into the human body. of abdominal pressure.
图5为实例1~6的细胞抗粘附图，可以看出随着硫酸钠浓度越高，总体上材料呈现出更加优异的抗粘附性能。Figure 5 shows the cell anti-adhesion graphs of Examples 1 to 6. It can be seen that as the sodium sulfate concentration increases, the material generally exhibits better anti-adhesion properties.
图6为内层水凝胶支架实验组（6wt%PVA/5wt%SA/1wt%HACC）和内层水凝胶支架空白组（不含壳聚糖季铵盐）的抗菌实验结果图，实验组对于金黄色葡萄球菌具有良好的杀灭作用，对于大肠杆菌基本没有作用。Figure 6 shows the antibacterial experimental results of the inner hydrogel scaffold experimental group (6wt%PVA/5wt%SA/1wt%HACC) and the inner hydrogel scaffold blank group (without chitosan quaternary ammonium salt). The group has good killing effect on Staphylococcus aureus, but has basically no effect on Escherichia coli.
图7为内层水凝胶支架实验组（6wt%PVA/5wt%SA/1wt%HACC）和内层水凝胶支架空白组（不含壳聚糖季铵盐）的血液相容性实验结果图，可以看出空白组和实验组的血液相容性分别为0.89%和1.51%，均低于5%（ISO 10993-4:2017）。Figure 7 shows the blood compatibility experimental results of the inner hydrogel stent experimental group (6wt%PVA/5wt%SA/1wt%HACC) and the inner hydrogel stent blank group (without chitosan quaternary ammonium salt) From the figure, it can be seen that the blood compatibility of the blank group and the experimental group are 0.89% and 1.51% respectively, both lower than 5% (ISO 10993-4:2017).
图8为空白组（材料仅为培养基）、内层水凝胶支架实验组（6wt%PVA/5wt%SA/1wt%HACC）、空白组（不含壳聚糖季铵盐）、 外层水凝胶支架实验组（使用0.7mol/ml硫酸钠进行盐析处理）和空白组（未经盐析处理）的CCK-8图。由检测结果可知，随着培养时间的延长材料的吸光度在不断增大，表明材料可促进L929(小鼠成纤维细胞)增殖，具有良好的生物活性。Figure 8 shows the blank group (material only culture medium), inner hydrogel scaffold experimental group (6wt%PVA/5wt%SA/1wt%HACC), blank group (without chitosan quaternary ammonium salt), outer layer CCK-8 images of the hydrogel scaffold experimental group (salting out treatment using 0.7mol/ml sodium sulfate) and the blank group (without salting out treatment). It can be seen from the test results that the absorbance of the material continues to increase as the culture time increases, indicating that the material can promote the proliferation of L929 (mouse fibroblasts) and has good biological activity.
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