Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (10): 1615-1621.doi: 10.3969/j.issn.2095-4344.1884
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Wei Chenxu1, He Yiwen1, Wang Dan1, Hou Jingxia1, 2, Xie Hui1, 2, Yin Fangzhou1, 2, Chen Zhipeng1, 2, Li Weidong1, 2
Received:
2019-05-08
Revised:
2019-05-22
Accepted:
2019-07-05
Online:
2020-04-08
Published:
2020-02-18
Contact:
Li Weidong, Researcher, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China; Key Laboratory of Chinese Medicine Processing in Jiangsu Province, Nanjing 210023, Jiangsu Province, China
About author:
Wei Chenxu, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Supported by:
CLC Number:
Wei Chenxu, He Yiwen, Wang Dan, Hou Jingxia, Xie Hui, Yin Fangzhou, Chen Zhipeng, Li Weidong. Research hotspots and progress of bone repair materials in tissue engineering[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(10): 1615-1621.
2.1 骨修复材料的特点 目前应用于骨修复的材料有数种,各有其利弊。公认的理想的骨修复材料应具有以下特点:①良好的生物组织相容性[5]:移植到体内后不引起排斥反应、炎症反应和毒性反应;②可塑性:材料可塑为任意的结构,植入后在体内仍可保持特定形状,具有记忆金属的特性;③可降解性:能在生物体内逐渐降解最终由自身骨组织所替代,且降解速率可根据骨组织形成中不同细胞再生速率而进行调整;④良好的力学性能[6]:良好的骨修复材料要能模拟生物体骨组织的结构、成分和性质,与骨组织力学性能相匹配;⑤可作为载体:调节生物活性因子的释放;⑥良好的骨传导性:有利于临近骨组织爬行替代;⑦较高的孔隙率及渗透性能[5]:适当的孔径与孔隙率利于物质交换,能够为细胞生长提供足够空间。 2.2 骨修复材料的种类 2.2.1 天然骨材料 天然骨,顾名思义就是来源于机体,非后天人工合成的骨修复材料。天然骨中成分均为机体的组成成分,所以临床使用安全性较高,天然骨主要有自体骨和(同种)异体骨两类,在骨修复中应用较为广泛,这类材料在骨修复领域中应用起步较早,研究也较为深入。 自体骨:自体骨是较为理想的骨缺损植入材料,是骨移植手术中骨修复材料的首选。自体骨来源于患者本身,临床上易于被患者接受且免疫排斥反应较低,甚至不引起排斥反应,生物相容性较好,骨诱导能力、骨传导能力和骨修复能力均较强,业内称之为“金标准”[7]。同时为避免感染,临床通常使用带血运的自体骨。张云峰等[8]对60例距骨骨软骨损伤患者实施自体软骨骨移植治疗,术后治疗效果显著,疼痛明显降低。高占巍等[9]对9例颧骨颧弓截骨术后骨不连患者实施自体骨移植修复,结果显示临床效果优异,2年内未出现严重并发症,移植骨成活性良好。但另一方面,临床应用中自体骨供骨量有限,术后易发生供区不良反应和神经损伤等问题,以及供体部位发病率高,易出现出血、慢性疼痛、感染、美容效果差等不良反应[10]。 异体骨:主要指同种异体骨,具有良好的骨传导性和骨诱导性,来源比自体骨较广,被广泛应用于填充骨空隙[11]、诱导局部组织的修复。马中瑞等[12]研究发现良性骨肿瘤患者采用异体骨手术12个月后愈合率达97.5%,并且初步愈合时间明显短于人工骨移植。GRACITELLI等[13]研究认为骨软骨同种异体骨移植是治疗膝关节软骨和骨缺损的有效办法,临床症状得到显著改善。膝关节同种异体骨移植有利于膝盖的修复并提升患者生活质量[14]。郜德龙等[15]回顾分析得出,同种异体骨Cage在修复腰椎骨时可提供早期稳定性和较高的融合率。但相对于自体骨,同种异体骨容易出现免疫排斥反应,有疾病传播的危险。同时,异体骨材料较难获得、价格不菲及刚性较低等也是其不足之处。 2.2.2 骨移植替代材料 单一成分的人工骨研究起步较早,目前在临床中已有应用;复合人工骨的研究目前还处于基础研究阶段,虽还有很多未解的难题,但仍有一定的研究成果,目前以复合有骨生长因子或种子细胞的复合材料居多。随着对原位组织再生理解的不断深入以及研究的不断拓展,骨组织工程的研究方向逐渐向基于药物和骨修复材料结合上转变,即将骨修复材料作为一种药物控释载体。下面将分类介绍骨修复材料及其优缺点。 天然高分子材料:目前此类材料常见的主要有胶原、透明质酸、壳聚糖[16](图2)、海藻酸盐、丝素蛋白、纤维蛋白等。总体来说,这类材料的优势在于具有较好的生物相容性,安全无毒,细胞亲和性良好。但同时由于各自天然成分的不同及来源不尽相同,也不可避免的存在着一些如质量重复性不佳等不足之处,见表1。 "
医用生物陶瓷材料:医用生物陶瓷材料有惰性材料与活性材料之分。惰性材料有氧化铝、氧化锆等。肖长江等[28]研究发现加入30 nm氧化铝粉,氧化铝陶瓷的硬度和抗弯强度有所改善。曾峰等[29]研究表明将氧化锆复合到氧化铝粉体中可增强断裂韧性。活性材料:①羟基磷灰石:是自然骨中的无机成分之一。近年来,亦有对纳米羟基磷灰石的临床研究报道[30],临床显示生物相容性良好,无不良反应;②磷酸三钙:WANG等[31]研究发现,磷酸钙陶瓷的相组成可能会调节植入物局部微环境中骨诱导因子的数量;③生物活性玻璃:是一种硅酸盐玻璃。COATHUP等[32]研究发现与具有相同形态的非硅酸盐相比,硅酸盐取代的磷酸钙骨替代材料的骨诱导能力增加。 总体来说,这类材料来源广泛,成本相对较低,生物相容性和骨传导性较好,可与组织表现出良好的亲和性,美中不足的是生物力学性能不足、脆性大。另外,在不同的植入部位上,陶瓷制作的孔径大小及孔隙率尚未有统一标准[33]。羟基磷灰石晶体结构见图4[34]。医用生物陶瓷材料的优缺点见表3。 "
其他新型材料:如以石墨烯材料和碳纳米管为主的碳素材料及脱细胞基质材料等。碳素材料以优良的导电性和热学性能,独特的机械性能,良好的生物相容性,使其在生物医学领域备受关注[49-50]。脱细胞基质是采用一定的方法去除组织或器官中的细胞等成分,获得的接近细胞外基质天然结构与形状、同时保留了活性成分的一种材料[51],具有较好的骨传导性和骨诱导能力[52],生物衍生骨材料在许多方面都具有显著的优势,比如孔隙结构和生物降解等方面,但是其生物力学性能不佳以及免疫原性等问题仍不能令人满意,有待于改善[53]。 随着3D打印技术的发展及个体化治疗的需求不断增长,3D打印的骨修复材料也应运而生,目前常用的3D打印技术有电子束熔融法和选择性激光融化技术[54]。3D打印制备的支架具有良好的生物相容性及物理性能,而且制备的支架更加符合骨修复部位所需的环境条件,但是也有其一定的局限性,比如孔隙率和孔径大小对支架性能的影响仍有一定的争议[55-56]。随着越来越多的生物材料被应用于骨修复,各种复合材料也如雨后春笋般的被研发而出,复合材料可以扬长避短,综合各种材料的优越性能,临床试验效果更佳。几种复合骨修复材料的主要优越性见表5。 "
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