CN109276759A - A biomimetic antibacterial abdominal wall repair material - Google Patents
A biomimetic antibacterial abdominal wall repair material Download PDFInfo
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Abstract
本发明公开了一种仿生抗菌腹壁修复材料,该腹壁修复材料包含猪小肠粘膜下层以及覆膜于该猪小肠粘膜下层一测的壳聚糖‑弹性蛋白纤维网层;且该壳聚糖‑弹性蛋白纤维网层为静电纺丝纳米级壳聚糖‑弹性蛋白纤维网。本发明通过将壳聚糖‑弹性蛋白纤维网层与猪小肠粘膜下层覆膜结合,使得到的腹壁修复材料的抗菌能力得到有效提高;同时,该腹壁修复材料的力学强度和降解性能满足腹壁修复要求,还可以促进血管生成而有利于组织再生,有助于解决腹壁修复材料现存技术瓶颈,有效改善腹壁缺损修复的治疗效果。The invention discloses a biomimetic antibacterial abdominal wall repair material. The abdominal wall repair material comprises a porcine small intestine submucosa and a chitosan-elastin fiber mesh layer coated on the porcine small intestine submucosa; and the chitosan-elasticity The protein fiber mesh layer is an electrospinning nano-scale chitosan-elastin fiber mesh. In the present invention, the antibacterial ability of the abdominal wall repair material is effectively improved by combining the chitosan-elastin fibrous mesh layer with the porcine small intestine submucosa membrane; at the same time, the mechanical strength and degradation performance of the abdominal wall repair material meet the requirements of abdominal wall repair. According to the requirements, it can also promote angiogenesis and facilitate tissue regeneration, help to solve the existing technical bottleneck of abdominal wall repair materials, and effectively improve the therapeutic effect of abdominal wall defect repair.
Description
技术领域technical field
本发明属于医用耗材技术领域,具体涉及一种仿生抗菌腹壁修复材料。The invention belongs to the technical field of medical consumables, and in particular relates to a bionic antibacterial abdominal wall repair material.
背景技术Background technique
腹壁修复材料的研发和应用是当前疝和腹壁外科研究的一个重要方向。目前的腹壁修复补片尚存在一些亟待解决的难题。它们的主要缺点仍然是生物活性低,导致血管化不良和植入物本身的细胞化不均匀,最终导致与周围组织缺乏整合和组织再生。最近腹壁修复中使用脱细胞基质代表了开发仿生移植物的努力,其特征在于更高的生物相容性和改善的体内性能。植入后,移植物经历以下命运之一:(i)新血管形成和新的ECM沉积;(ii)纤维化包囊;(iii)再吸收/降解。因此,理想的移植物应该有利于早期新血管形成,完全生物相容和仿生,以促进再生免疫反应,而不是可能导致纤维化包裹的炎症。此外,它应该允许招募干细胞和成人组织特异性细胞,以最终恢复组织功能。有学者目前已经研究了用于腹壁重建的仿生补片的生物学启发方法。The development and application of abdominal wall repair materials is an important direction of current hernia and abdominal wall surgery research. The current abdominal wall repair patch still has some problems that need to be solved urgently. Their main disadvantage remains low biological activity, resulting in poor vascularization and uneven cellularization of the implant itself, ultimately resulting in a lack of integration with surrounding tissues and tissue regeneration. The recent use of acellular matrices in abdominal wall repair represents an effort to develop biomimetic grafts characterized by higher biocompatibility and improved in vivo performance. After implantation, the graft undergoes one of the following fates: (i) neovascularization and new ECM deposition; (ii) fibrotic encapsulation; (iii) resorption/degradation. Therefore, ideal grafts should favor early neovascularization, be fully biocompatible, and biomimetic to promote regenerative immune responses, rather than inflammation that can lead to fibrotic encapsulation. Furthermore, it should allow the recruitment of stem cells and adult tissue-specific cells to ultimately restore tissue function. Some scholars have studied biologically inspired methods of bionic patches for abdominal wall reconstruction.
利用仿生学的总体原则来解决这一临床需求,以创建更好地类似于目标组织的组成,结构和机械特性的材料。胶原蛋白和弹性蛋白是体内几乎所有组织的细胞外基质(ECM)中最丰富的成分,为细胞附着,迁移和组织提供了必要的线索。胶原蛋白和弹性蛋白也是腹壁细胞外基质的两个主要成分,其比例或代谢的变化与腹壁疝发生有关。脱细胞猪小肠粘膜下层是一种富含活性因子的天然生物材料,主要由胶原蛋白以及一些生长因子和信号分子组成,具有优良的生物活性,在应用于多种组织缺损修复中,具体较突出的生物学优势,可获得组织结构和功能上的重建。弹性蛋白为组织提供弹性和变形性。弹性蛋白的特性对特定组织功能(例如真皮,血管,肌肉)至关重要。此外,一些证据表明可溶性弹性蛋白通过促进血管生成而有利于组织再生。因此,猪小肠粘膜下层和弹性蛋白复合材料可用于腹壁结构和组成上的仿生修复。This clinical need is addressed using the overarching principles of biomimicry to create materials that better resemble the composition, structure, and mechanical properties of target tissues. Collagen and elastin are the most abundant components of the extracellular matrix (ECM) of nearly all tissues in the body, providing essential cues for cell attachment, migration, and organization. Collagen and elastin are also two major components of the extracellular matrix of the abdominal wall, and changes in their ratio or metabolism are associated with the occurrence of abdominal wall hernias. Decellularized porcine intestinal submucosa is a natural biomaterial rich in active factors, mainly composed of collagen and some growth factors and signal molecules. It has excellent biological activity and is used in the repair of various tissue defects. The biological advantage of the tissue structure and function can be obtained. Elastin provides elasticity and deformability to tissues. The properties of elastin are critical for specific tissue functions (eg, dermis, blood vessels, muscle). Furthermore, some evidence suggests that soluble elastin facilitates tissue regeneration by promoting angiogenesis. Therefore, porcine small intestinal submucosa and elastin composites can be used for biomimetic repair of abdominal wall structure and composition.
现在急需一种疝修补材料能够主动抗菌,能在污染和感染创面进行应用。污染和感染情况下的腹壁缺损在战创伤、交通伤、同时进行肠道手术等情况下非常常见,目前对此类腹壁缺损多是一期清创、二期再以材料行确定性腹壁修补,不仅延长了治疗时间,给患者造成较长时问的痛苦,而且造成了卫生经济、社会劳动力的损失。要解决以上难题,就必须将抗菌材料引入到腹壁修复材料中。壳聚糖是一种可降解材料,属于天然聚阳离子生物多糖,具有广谱抗菌作用。有关壳聚糖的抗菌机制主要有2种观点。一种是根据壳聚糖的聚阳离子性质提出的、以细菌带负电荷的细胞膜为靶位的机制,其指出壳聚糖分子中的质子化铵与细胞带负电荷的细胞膜作用,吸附细菌,使其出现凹陷、变形和泄露;另一种是以细菌分子中的DNA为靶位的抗菌机制,其指出壳聚糖在透过损伤的细胞壁后进入细胞内,进一步与胞质发生作用,扰乱了细菌DNA分子的转录。壳聚糖还有良好的生物相容性和生物降解性能,可显著提高纤维细胞增殖、迁移速度,能促进细胞外基质的合成,能为缺损部位营造良好的愈合环境。There is an urgent need for a hernia repair material that can be actively antibacterial and can be applied to contaminated and infected wounds. Abdominal wall defects under the condition of pollution and infection are very common in combat trauma, traffic injury, and intestinal surgery at the same time. At present, most of these abdominal wall defects are debridement in one stage, and then repaired with materials in the second stage. It not only prolongs the treatment time and causes long-term pain to patients, but also causes the loss of health economy and social labor force. To solve the above problems, it is necessary to introduce antibacterial materials into abdominal wall repair materials. Chitosan is a kind of degradable material, which belongs to natural polycationic biopolysaccharide and has broad-spectrum antibacterial effect. There are two main viewpoints on the antibacterial mechanism of chitosan. One is a mechanism based on the polycationic properties of chitosan, which targets the negatively charged cell membrane of bacteria. Make it dented, deformed and leaked; another antibacterial mechanism is based on the DNA in the bacterial molecule as the target, which points out that chitosan enters the cell after passing through the damaged cell wall, and further interacts with the cytoplasm to disrupt the transcription of bacterial DNA molecules. Chitosan also has good biocompatibility and biodegradability, which can significantly improve the proliferation and migration speed of fibroblasts, promote the synthesis of extracellular matrix, and create a good healing environment for the defect site.
发明内容SUMMARY OF THE INVENTION
本发明的目的旨在提供一种仿生抗菌腹壁修复材料,适用于疝和腹壁外科修复,有效改善临床腹壁缺损修复的治疗效果。The purpose of the present invention is to provide a bionic antibacterial abdominal wall repair material, which is suitable for hernia and abdominal wall surgical repair, and effectively improves the therapeutic effect of clinical abdominal wall defect repair.
为了解决上述技术问题,本发明具体通过以下技术方案实现:In order to solve the above-mentioned technical problems, the present invention is specifically realized through the following technical solutions:
一种仿生抗菌腹壁修复材料,包括猪小肠粘膜下层和壳聚糖-弹性蛋白纤维网层,所述的壳聚糖-弹性蛋白纤维网层覆膜于猪小肠粘膜下层一侧。A biomimetic antibacterial abdominal wall repair material comprises a porcine small intestine submucosa and a chitosan-elastin fibrous mesh layer, wherein the chitosan-elastin fibrous mesh layer is coated on one side of the pig small intestine submucosa.
所述的壳聚糖-弹性蛋白纤维网层为纳米级壳聚糖-弹性蛋白纤维网层,所述的聚糖-弹性蛋白纤维网层的纤维直径为80~230纳米,厚度为50~300微米。纳米级的壳聚糖-弹性蛋白纤维网有利于更好地发挥壳聚糖-弹性蛋白纤维层对猪小肠粘膜下层在修复效果上的抗菌作用。The chitosan-elastin fiber mesh layer is a nano-scale chitosan-elastin fiber mesh layer, and the fiber diameter of the polysaccharide-elastin fiber mesh layer is 80-230 nanometers, and the thickness is 50-300 nanometers. microns. The nano-scale chitosan-elastin fiber mesh is beneficial to better exert the antibacterial effect of the chitosan-elastin fiber layer on the repair effect of the porcine small intestine submucosa.
所述的壳聚糖-弹性蛋白纤维网层采用静电纺丝的方法制备得到,与猪小肠粘膜下层覆膜结合,进一步优化了腹壁修复材料的医用性能。The chitosan-elastin fiber mesh layer is prepared by the method of electrospinning, and is combined with the submucosa membrane of the small intestine of pigs, which further optimizes the medical performance of the abdominal wall repair material.
所述的猪小肠粘膜下层为4层脱细胞猪小肠粘膜下层材料。The porcine small intestine submucosa is 4 layers of decellularized porcine small intestine submucosa material.
本发明的有益效果为:The beneficial effects of the present invention are:
本发明将壳聚糖-弹性蛋白纤维网层与猪小肠粘膜下层覆膜结合,使得到的腹壁修复材料具有仿生性、抗菌性和生物活性。同时,该腹壁修复材料的力学强度和降解性能满足腹壁修复要求,还可以促进血管生成而有利于组织再生,有助于解决腹壁修复材料现存技术瓶颈,有效改善腹壁缺损修复的治疗效果。In the invention, the chitosan-elastin fiber mesh layer is combined with the submucosa membrane of the small intestine of pigs, so that the obtained abdominal wall repair material has biomimetic properties, antibacterial properties and biological activity. At the same time, the mechanical strength and degradation performance of the abdominal wall repair material meet the requirements of abdominal wall repair, and can also promote angiogenesis to facilitate tissue regeneration, help to solve the existing technical bottleneck of abdominal wall repair materials, and effectively improve the therapeutic effect of abdominal wall defect repair.
附图说明Description of drawings
图1是本发明实施例1仿生抗菌腹壁修复材料的结构示意图;其中1为猪小肠粘膜下层,2为壳聚糖-弹性蛋白纤维网层;1 is a schematic structural diagram of a biomimetic antibacterial abdominal wall repair material in Example 1 of the present invention; wherein 1 is the submucosa of pig small intestine, and 2 is the chitosan-elastin fiber mesh layer;
图2是本发明实施例1猪小肠粘膜下层的扫描电镜图,其中图2(a)为低放大倍数,图2(b)为高放大倍数;Fig. 2 is the scanning electron microscope picture of the pig small intestine submucosa in Example 1 of the present invention, wherein Fig. 2 (a) is a low magnification, and Fig. 2 (b) is a high magnification;
图3是本发明实施例1猪小肠粘膜下层的横截面图;3 is a cross-sectional view of the porcine small intestine submucosa in Example 1 of the present invention;
图4是本发明实施例1仿生抗菌腹壁修复材料的扫描电镜图,其中图4(a)为低放大倍数,图4(b)为高放大倍数;Fig. 4 is the scanning electron microscope image of the bionic antibacterial abdominal wall repair material in Example 1 of the present invention, wherein Fig. 4(a) is a low magnification, and Fig. 4(b) is a high magnification;
图5是本发明实施例1仿生抗菌腹壁修复材料的横截面图。5 is a cross-sectional view of a bionic antibacterial abdominal wall repair material in Example 1 of the present invention.
具体实施方式Detailed ways
下面将结合本发明具体的实施例,对本发明技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。The technical solutions of the present invention will be clearly and completely described below with reference to specific embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
实施例1Example 1
一种仿生抗菌腹壁修复材料,如图1所示,包含猪小肠粘膜下层以及覆膜于猪小肠粘膜下层一侧的壳聚糖-弹性蛋白纤维网层。A biomimetic antibacterial abdominal wall repair material, as shown in Figure 1, comprises a porcine small intestine submucosa and a chitosan-elastin fibrous mesh layer coated on one side of the porcine small intestine submucosa.
上述的壳聚糖-弹性蛋白纤维网层的厚度为50微米,纳米级壳聚糖-弹性蛋白纤维的纤维直径为100纳米,且该纳米级壳聚糖-弹性蛋白纤维网采用静电纺丝制备而得。如图2和图3,上述的猪小肠粘膜下层为4层脱细胞猪小肠粘膜下层材料。The thickness of the above-mentioned chitosan-elastin fiber mesh layer is 50 microns, the fiber diameter of the nano-scale chitosan-elastin fiber is 100 nanometers, and the nano-scale chitosan-elastin fiber mesh is prepared by electrospinning And get. As shown in Fig. 2 and Fig. 3, the above-mentioned porcine small intestinal submucosa is a 4-layer decellularized porcine small intestinal submucosa material.
如图4和图5所示,制备所得仿生抗菌腹壁修复材料的扫描电镜图,由图4可知仿生抗菌腹壁修复材料中的壳聚糖-弹性蛋白纤维表面光滑,纤维直径为纳米量级;由图5可知仿生抗菌腹壁修复材料中的两层材料结合紧密。As shown in Figure 4 and Figure 5, the scanning electron microscope images of the obtained biomimetic antibacterial abdominal wall repair material are prepared. It can be seen from Figure 4 that the chitosan-elastin fibers in the biomimetic antibacterial abdominal wall repair material have a smooth surface, and the fiber diameter is on the order of nanometers; Figure 5 shows that the two layers of materials in the biomimetic antibacterial abdominal wall repair material are closely combined.
实施例2Example 2
一种仿生抗菌腹壁修复材料,包含猪小肠粘膜下层以及覆膜于猪小肠粘膜下层一侧的壳聚糖-弹性蛋白纤维网层A biomimetic antibacterial abdominal wall repair material, comprising a porcine small intestine submucosa and a chitosan-elastin fibrous mesh layer coated on one side of the porcine small intestine submucosa
本实施方式中的纳米级壳聚糖-弹性蛋白纤维网层的厚度为100微米,纳米级壳聚糖-弹性蛋白纤维的纤维直径为150纳米,且该纳米级壳聚糖-弹性蛋白纤维网采用静电纺丝制备而得。本实施方式中的猪小肠粘膜下层为4层脱细胞猪小肠粘膜下层材料。In this embodiment, the thickness of the nano-scale chitosan-elastin fiber mesh layer is 100 microns, the fiber diameter of the nano-scale chitosan-elastin fiber is 150 nanometers, and the nano-scale chitosan-elastin fiber mesh is Prepared by electrospinning. The porcine small intestinal submucosa in this embodiment is a 4-layer decellularized porcine small intestinal submucosa material.
实施例3Example 3
一种仿生抗菌腹壁修复材料,包含猪小肠粘膜下层以及覆膜于猪小肠粘膜下层一侧的纳米级壳聚糖-弹性蛋白纤维网层。A biomimetic antibacterial abdominal wall repair material comprises a porcine small intestine submucosa and a nano-scale chitosan-elastin fiber mesh layer coated on one side of the porcine small intestine submucosa.
本实施方式中的纳米级壳聚糖-弹性蛋白纤维网层的厚度为150微米,纳米级壳聚糖-弹性蛋白纤维的纤维直径为200纳米,且该纳米级壳聚糖-弹性蛋白纤维网采用静电纺丝制备而得。本实施方式中的猪小肠粘膜下层为4层脱细胞猪小肠粘膜下层材料。In this embodiment, the thickness of the nano-scale chitosan-elastin fiber mesh layer is 150 microns, the fiber diameter of the nano-scale chitosan-elastin fiber is 200 nanometers, and the nano-scale chitosan-elastin fiber mesh is Prepared by electrospinning. The porcine small intestinal submucosa in this embodiment is a 4-layer decellularized porcine small intestinal submucosa material.
尽管已经示出和描述了本发明的实施例,对于本领域的普通技术人员而言,可以理解在不脱离本发明的原理和精神的情况下可以对这些实例进行多种变化、修改、替换和变型,本发明的范围由所附权利要求及其等同物限定。Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principle and spirit of the invention Variations, the scope of the invention is defined by the appended claims and their equivalents.
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