CN110234364A - 纳米多孔生物人工骨组织复合物的制备方法 - Google Patents

纳米多孔生物人工骨组织复合物的制备方法 Download PDF

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CN110234364A
CN110234364A CN201880006841.XA CN201880006841A CN110234364A CN 110234364 A CN110234364 A CN 110234364A CN 201880006841 A CN201880006841 A CN 201880006841A CN 110234364 A CN110234364 A CN 110234364A
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帕利·纳齐尔
拉马·纳齐尔
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Abstract

本发明涉及了一种纳米多孔生物人工骨组织复合物的工艺，是针对在与宿主骨组织结合时，预防人体免疫的反应，同时减少了其整合的周期。本发明纳米多孔生物复合物由多种成分复配而成；羟基磷灰石(HA)或/和α‑或β‑磷酸三钙(α‑或β‑TCP)。聚己内酯(PCL)或聚乳酸(PLA)。将水加入任何佳乐施溶液或是凝胶，以制造本发明复合物可注射的溶液或是凝胶。由任何胶原组织构成的物质。重组人血管内皮生长因子。在化合物所有的硬化和最终过程完成后，任何丙烯酸酯立即以超声波处理。

Description

纳米多孔生物人工骨组织复合物的制备方法
本发明涉及了一种纳米孔生物人工骨组织复合物的工艺工程，针对与宿主骨组织结合时的人体免疫反应的预防，同时减少了其整合的周期。因为其瞬时硬化性质和可瞬时整合于人体任一部份骨架内，所以组合物可让任何可植入装置实时移植到该生物复合物中。该纳米多孔生物复合材料第一成分为羟基磷灰石(HA)，或/和α-或β-磷酸三钙(a-或β-TCP)或/和由组合HA和TCP而生成的双相磷酸钙(BCP)，或/和颗粒不超过99nm的硫酸钙(CaSO4)。下一成份是聚己内酯(PCL)或颗粒也不超过99nm的聚乳酸(PLA)。其他成分为：佳乐施或是任何佳乐施溶液或凝胶，之后加入一定量的水以形成本复合物的凝胶或是可注射溶液。之后，任何含有结缔胶原组织(f.ex cagut等)组成的任何物质。再之后，本发明提供了一种重组人体血管内皮生长因子A165(rhVEGF-A165)，其剂量是低于人体血管内皮细胞(HUVEC)增值之剂量依赖性的最终化合物的1-3ng ml。然后，任何作为分子配体种类的丙烯酸酯类(氰基丙烯酸酯类或磺内酯类化合物等)，在当所有该化合物的硬化和最终过程是经过一段小于60秒的时间、且频率介于24到32Khz超声波而立即获取。不同成分的比例是可变的，并且可以分别对应治疗的骨的类型和形式作出调适。在任何情况下，化合物的第一成分(HA或a-或β-TCP等)与PCL或/和PLA的比例为所得中间体化合物的58％-66％。对于0.6ml的复合物而言，丙烯酸酯(氰基丙烯酸酯或磺内酯等)不少于2滴，且不超过6滴。使用三维绘图软件(3D CAD)建模和压制成型，可以利用此复合物来制成制作任何骨骼(人类或动物)。β-TCP可以用生物可降解的Fe-Mg金属相或Fe-Ag纳米复合材料来增强。在任何种类的接合部位中，将会加入相关的涂层(例如，钛亚硝酸盐，也被称为TiNite(TiN))涂层或类钻石碳(DLC)涂层等。在脊椎处则可将可生物兼容性磷脂加入该生物复合物中。
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Claims (15)

1.第一种成分(HA或/和α或/和β-或β-TCP等)的颗粒大小尺寸必须透过适合本程序任何可实施以及核可的制程并配合着适切的冷却措施(f ex高能研磨机等)来减少。
2.通过两种细胞的相互作用使得骨再生成为可能：成骨细胞和破骨细胞。破骨细胞是直径约为50μm的巨细胞，它能独立吸收(破坏)老骨。另一方面，成骨细胞是直径约为10μm的小细胞，透过与许多其他细胞协同作用，形成新的骨。透过骨再吸收和骨形成的回路，骨总是再生。
3.如权利要求1所述，其PCL或PLA的颗粒尺寸必须透过适合本程序任何可实施以及核可的制程并配合着适切的冷却措施(f ex高能研磨机等)来减少。
4.所述第一种成分(HA或/和α或/和β-TCP或/和等))和PCL或/和PLA的联合，可利用适于本程序的任何实验室混合器而成为可能。
5.具有人体成骨细胞单一培养以及人体成骨结胞内皮细胞共同培养的β-TCP-15Fe复合物显示着这种组成物对于两种细胞的生长以及存活而言是生物兼容的，且这细胞分别在骨形成和血管生成表现出组织特异性标记。
6.生物可吸收的β-TCP-聚合物和Fe-Ag纳米复合材料可以是化合物的一部分。
7.如权利要求4所述，并以实验室研磨机加入施乐佳或是施乐佳溶液或凝胶，直到复合材料整体转换成为凝胶，并加入水以获得可用的凝胶。
8.向上述溶液中加入水直至转化为可注射溶液。
9.在实验室研磨机的帮助下，对含有胶原组织(f。ex。cagut等)的任何元素加以研磨，直到获得尽可能尽可能小的颗粒为止；依据于待治疗的骨的形式和类型，肠线或是任何含有结缔胶原组织物质的剂量，都是可变的。
10.将含有结缔胶原组织以及任何丙烯酸酯滴的任何元素附着到与超声处理完成的外科手术近处的化合物上。
11.藉由这复合物，在进行美容、创伤以及骨科手术时，准备人工骨头是相当容易的。
12.由这种生物复合物制成的移植和接枝都可避免形成于任何免疫反应，而其他则可能对受体有许多反应和影响，特别是那些基于动物骨骼的反应和影响。
13.在体外使用3D CAD建模和压制成形来构建骨头，同时也可使用这种复合物和白色，表面光滑的天然骨头来进行移植；所得到的移植物与天然骨在硬度，扭转和屈曲中的机械表现上是相当的。
14.在关节中，TiN或DLC涂层或在移植物上的任何其它类似的碳涂层赋予其类似的天然摩擦。
15.重组是为此生物复合物一部份的人血管内皮生长因子A165(rhVEGF-A165)是为微血管灌注强化，以及在活体组织中有组织的结构网络内发展新的微血管毛细现象都是一种强而有效的因子。
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