CN105919696A - 一种具有力学梯度仿生人工骨支架的制备方法 - Google Patents
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- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Abstract
本发明公开了一种具有力学梯度仿生人工骨支架的制备方法。该方法首先将人工骨支架CAD模型由下至上均匀分割成N层截面并将每层截面由里到外分为四部分,然后将羟基磷灰石、明胶、生物粘结剂等材料按四种不同比例混合成打印原材料。最后将四种不同比例的混合材料依次有序地挤压打印到每层截面的四部分中。在本发明中,由于每层截面各部分使用的打印原材料各组分比例不同,从而使得各部分具有不同的力学性能,利用此方法制备的人工骨支架具有更好的力学性能和梯度。
Description
技术领域
本发明提出了一种具有力学梯度仿生人工骨支架的制备方法。主要涉及到人工骨支架材料的研究、骨移植技术的研究、人体骨骼结构等方面的研究。
背景技术
骨骼是人体运动系统的重要组成部分,起着支撑、保护身体的作用。但骨骼疾病是现代社会影响人们身体健康的重要疾病之一。骨缺损是目前一种常见的骨骼疾病,而利用骨移植手术进行骨修复是治疗骨缺损的重要方式之一。
骨修复材料是进行骨移植、修复骨缺损的重要材料。传统骨移植多采用自体骨或者异体骨进行移植。自体骨虽然一直是进行骨修复和移植的理想材料,但存在供体不足、患者的二次损伤、出血量高、供骨部位容易出现并发症等缺点。而如果用异体骨取代自体骨移植则存在着出现排斥反应等风险,因此,利用人工骨来代替天然骨进行骨移植的研究越来越受到科研人员的重视。
人体骨组织主要由羟基磷灰石与胶原两大部分组成。羟基磷灰石是一种无机物质,其具有良好的生物相容性和生物活性,植入骨组织后能在界面上和骨形成很强的化学性键合,具有骨传导和骨诱导性,目前羟基磷灰石生物陶瓷已经用于临床上骨的修复替换,本次发明拟采用羟基磷灰石作为复合打印材料中的一种组分。
羟基磷灰石虽然是人体骨的无机组成成分,但其存在生物降解性低等缺点。因此为弥补这些缺点,本发明拟在复合材料中加入一种具有良好生物降解性的材料。为使复合材料成分更接近人体骨组织的组成成分,本次发明选用明胶作为此种材料。明胶是由动物皮肤、肌膜等结缔组织中的胶原部分降解而成的粉粒,其是非常重要的天然生物高分子材料之一,目前已被广泛应用于食品、医药等行业。
3D打印,即快速成型技术的一种,它是一种以数字模型文件为基础,运用粉末状金属或塑料等可粘合材料,通过逐层打印的方式来构造物体的技术。当前,利用3D打印技术进行人工骨支架制备已经成为一种趋势。目前已出现利用激光烧结法、骨水泥挤压法、粉末叠层法等方法进行人工骨支架制备。但目前在人工骨支架制备过程中,大多数研究只是只是集中于人工骨支架三维模型的建立、人工骨支架微观结构的设计、人工骨支架制备材料的优化、人工骨支架植入人体后的相容性及可降解性以及人工骨支架孔隙率的控制等方面的研究,但对于人工骨支架力学性能的研究一般较少,即便是有也只是集中于整体骨支架的力学性能的实现,和天然人体骨的力学性能相比还是有很大的差距。
公开号为CN102429745A的发明专利提出了一种横向梯度孔结构的纳米人工骨支架及其制备方法。该方法将聚己内酯溶入已经制备好的羟基磷灰石溶胶中从而制备出不同比例的HA/PCL溶胶,然后将HA/PCL溶胶层层浇铸到特制的模具中制得人工骨支架。该发明将人工骨支架由里到外分不同部分进行浇模,在一定程度上实现了骨支架的横向梯度。但本方法还存在以下问题:
该发明采用向模具中浇铸材料的方法进行制备骨支架,采用的模具形状单一(该发明中模具采用圆柱形),不能符合人工骨三维结构复杂曲面的要求。该方法所制备的骨支架层与层之间连接不够紧密,容易出现分层现象,引起应力集中以及骨支架的空隙结构不能得到保障,此外,该发明选用二甲基乙酰胺作为溶剂,虽然最后洗去溶剂,但还是会造成骨支架上有残留,植入人体内对人体有害。
公开号CN102697584A的发明专利提出了一种孔隙连通性可控的人工骨支架的制备方法。该发明将生物陶瓷小球和生物可降解小球通过离散分析颗粒流软件按一定比例进行混合后通过喷洒生物胶黏剂进行粘结的方法实现人工骨支架的制备。其特点是利用生物可降解小球的在人体内的降解性来控制实现骨支架的孔隙率。但本方法存在以下问题:
该发明只是通过控制生物可降解小球的比例来控制人工骨支架的孔隙连通性,并没有实现人工骨支架的优良的力学性能。
因此,为克服传统骨移植手术中存在供体不足、排斥反应等及新型人工骨支架制备工艺无法很好地实现横向力学梯度分布等问题,本发明提出一种具有力学梯度仿生人工骨支架的制备方法。
发明内容
针对背景中提出的当前人工骨支架制备过程中存在的问题,本发明采用的技术方案是:一种具有力学梯度仿生人工骨支架的制备方法。
具体包括如下步骤:
步骤1、首先利用计算机建立起将要打印的骨支架的三维CAD模型,然后将已建立的人工骨支架CAD模型由下至上均匀分割成N个等间距的二维截面。
步骤2、根据天然骨组织各部分的力学特性,将步骤1分割好的每层二维截面由内到外分成4个梯度a、b、c、d,其中a区形状是具有一定直径的类圆形,b、c、d为一定宽度的类圆环形。
步骤3、将羟基磷灰石、明胶、生物粘结剂分别按照质量比为(1) 10%:70%:20%、(2)15%:60%:25%、(3) 20%:50%:30%、 (4) 25%:40%:35%四种比例混合打印原材料。
步骤4、将步骤3中制备的(1)、(2)、(3)、(4)四种混合材料分别放入自制的挤压成型机的挤压喷头(Ⅰ)、(Ⅱ)、(Ⅲ)、(Ⅳ)中。
步骤5、将步骤4喷头(Ⅰ)、(Ⅱ)、(Ⅲ)、(Ⅳ)中放入的原材料分别挤压至二维截面的a、b、c、d四部分中,形成第一层。然后按照分割的每层二维截面的轨迹逐层挤压,直到N层截面打印完毕。
步骤6、待最后一层截面打印完毕,取出制备好的骨支架进行后续的干燥与完善处理。
进一步的优选:
1.选用羟基磷灰石材料时要注意尽量选用较小半径的材料,一般选用30nm-50nm之间的材料。
2.明胶颗粒事先利用粉碎技术处理为粉末状。
3.生物粘结剂一般包括医用胶水、医药级聚乙烯醇等,可以选择其中一种。
本发明的创新点是:
1、创新性的提出采用将每层截面分部分打印的新型方法进行加工制备骨支架。
2、每层截面各部分采用的粉末混合材料的组成比例各不相同,从而实现骨支架横向力学梯度分布。
3、各部分混合材料中生物粘结剂的比例各不相同,从而实现各部分粘结性能的不同并进而实现对人工骨支架横向力学性能的控制。
以下通过具体实施实例对本发明作进一步说明。
具体实施实例:
本实施实例采用快速成型机中的挤压成型机,该种成型机利用将原材料分层挤压的技术制备骨支架。其包括多个挤压喷头、成型工作台等装置。本次具体实例拟利用挤压成型机快速成型制作一个底面直径为12mm,高度为30mm的圆柱形人工骨支架。
步骤1、首先利用计算机建立起本次需要打印的骨支架的CAD模型,然后利用分层软件将本次需打印的具体实例骨支架CAD模型由下至上均匀等间距地分割成60层二维截面,每层厚度为0.5mm。
步骤2、将步骤1分割好的每层二维截面由里到外依次分成四部分并由里到外分别编号为a、b、c、d这四个区,其中中心的a区是直径为6mm的圆,b、c、d三区分别是宽度为1mm的圆环形。
步骤3、
步骤3.1、首先将用到的明胶利用粉碎技术粉碎成粉末状。
步骤3.2、本次实施实例选用医药级聚乙烯醇作为生物粘结剂。
步骤3.3、将粒径为40mm羟基磷灰石、粉末状的明胶、医药级聚乙烯醇分别按照质量比为(1) 10%:70%:20%、(2) 15%:60%:25%、(3) 20%:50%:30%、(4) 25%:40%:35%四种比例混合打印原材料。
步骤4、将步骤3中制备的(1)、(2)、(3)、(4)四种混合材料分别放入挤压成型机的挤压喷头(Ⅰ)、(Ⅱ)、(Ⅲ)、(Ⅳ)中。
步骤5、将步骤4喷头(Ⅰ)、(Ⅱ)、(Ⅲ)、(Ⅳ)中的原材料分别挤压至各层二维截面的a、b、c、d四部分中,形成第一层。然后按照建立的每层模型轨迹逐层挤压,直到60层截面打印完毕。
步骤6、待最后一层截面打印完毕,取出制备好的骨支架进行后续的干燥与完善处理。
本次实施实例制备的人工骨支架的力学性能(压缩模量MPa)经检测分别为a区24.8,b区32.1,c区39.6,d区48.5。
Claims (1)
1.一种具有力学梯度仿生人工骨支架的制备方法,具体包括如下步骤:
步骤1、首先利用计算机建立起将要打印的骨支架的三维CAD模型,然后将已建立的人工骨支架CAD模型由下至上均匀分割成N个等间距的二维截面;
步骤2、根据天然骨组织各部分的力学特性,将步骤1分割好的每层二维截面由内到外分成4个梯度a、b、c、d,其中a区形状是具有一定直径的类圆形,b、c、d为一定宽度的类圆环形;
步骤3、将羟基磷灰石、明胶、生物粘结剂分别按照质量比为(1)10%:70%:20%、(2)15%:60%:25%、(3) 20%:50%:30%、 (4) 25%:40%:35%四种比例混合打印原材料;
步骤4、将步骤3中制备的(1)、(2)、(3)、(4)四种混合材料分别放入自制的挤压成型机的挤压喷头(Ⅰ)、(Ⅱ)、(Ⅲ)、(Ⅳ)中;
步骤5、将步骤4喷头(Ⅰ)、(Ⅱ)、(Ⅲ)、(Ⅳ)中放入的原材料分别挤压至二维截面的a、b、c、d四部分中,形成第一层,然后按照分割的每层二维截面的轨迹逐层挤压,直到N层截面打印完毕;
步骤6、待最后一层截面打印完毕,取出制备好的骨支架进行后续的干燥与完善处理。
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