骨组织工程支架材料修复牙槽嵴裂的研究进展

doi:10.7518/gjkq.2018.05.018

摘要/Abstract

摘要：

牙槽嵴裂是一种常见的颌面部发育畸形,传统的骨移植治疗存在骨量有限、术后易出现并发症等缺陷。骨组织工程修复骨缺损消除了自体骨移植的缺点,为牙槽嵴裂修复提供了新途径,成为当前的研究热点。骨组织工程研究的中心环节是支架材料,本文就骨组织工程支架及其修复牙槽嵴裂的研究状况作一综述。

关键词: 牙槽嵴裂, 骨组织工程, 支架材料

Abstract:

Alveolar cleft is a common craniofacial abnormality. Traditional treatments, including autogenous bone grafting, suffer from limited bone resources and high incidence of post-operative complications. These problems can be solved by bone tissue engineering, which offers a superior approach to repair the alveolar cleft. This article reviews the progress of using various scaffolds for repairing alveolar cleft.

Key words: alveolar cleft, bone tissue engineering, scaffold

中图分类号:

R782.13

易芳,王斯任,褚衍昊,卢燕勤. 骨组织工程支架材料修复牙槽嵴裂的研究进展[J]. 国际口腔医学杂志, 2018, 45(5): 603-610.

Fang Yi,Siren Wang,Yanhao Chu,Yanqin. Lu. Research progress on the repair of alveolar cleft with bone tissue engineering scaffolds[J]. Inter J Stomatol, 2018, 45(5): 603-610.

图/表 4

表 1

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表 4

负载细胞、生长因子支架材料修复牙槽嵴裂的研究应用"

支架材料	负载细胞、生长因子种类	应用	对照组	评价方法	实验结果	随访时间/月
碳酸羟	BMSC	3只比格犬双侧牙	HA	X线、组织	植骨区实验和对照组的牙齿移动距离没有差异;牙齿移动	6
磷灰石^[35]		槽嵴裂,移植术		学染色	速率实验组一致,对照组不一致;对照组观察到牙根吸收
		后6个月对上颌牙
		加力
β-TCP^[36]	BMSC	6只犬双侧牙槽	β-TCP、自	荧光标记、X	侧切牙移动距离、剩余牙槽骨高度、尖牙与侧切牙间的	5
		嵴裂,术后2个	体髂骨	线、组织学	新骨生成百分比：实验组（5.345±0.936） mm,73.60%±
		月对上颌牙加力		分析、组织	6.51%,70.79%±7.02%;单纯支架组（6.986±1.412） mm,
				形态学分析	56.31%± 7.72%,54.98%±9.22%;自体骨移植组（4.665±
					0.483） mm,72.42%±8.72%,78.68% ±4.91%
β-TCP^[37]	MSC	10只比格犬单侧	空白对照	X线、CT、	实验组骨内矿物质含量是对照组的3倍,对照组缺损被纤	3.25
		牙槽嵴裂		组织学分析	维组织充填,而实验组缺损被新生骨取代
β-TCP^[38]	BMSC	14只比格犬单侧	空白组、	荧光标记、	实验组新骨形成和矿化的速度较单纯自体骨移植组明显加	2
		牙槽嵴裂结合上	自体髂骨	X线螺旋CT、	快,骨吸收明显减少,与自体髂骨移植结合快速扩弓组无
		颌快速扩弓	组织、自	苏木精-伊红	明显差别
			体髂骨移	染色、组织
			植结合上	形态学分析
			颌快速扩
			弓组
支架材料	负载细胞、生长因子种类	应用	对照组	评价方法	实验结果	随访时间/月
HA-TCP^[40]	未分化MSC、分化MSC	84只Lewis大鼠单侧牙槽嵴裂	HA-TCP、空白对照	CBCT、组织形态学分析、组织形态测定	骨缺损的体积和宽度：负载未分化MSC组（4.08± 1.36） mm³、（2.39 ± 0.23） mm,负载分化MSC组（5.00±0.84）mm³、（2.53±0.22） mm,单纯支架组（5.50±1.05） mm³、（2.70±0.66） mm,空白对照组（6.86±3.21） mm³、（2.63±0.52）mm	1.5
HA-TCP^[41]	MSC	4只犬双侧牙槽嵴裂	对侧自体胫骨骨密质	组织形态学分析	骨形成率对照组为70%,实验组为5%	2
Col^[42]	牙髓干细胞	60只Wistar大鼠牙槽嵴裂	自体髂骨、Col	苏木精-伊红染色	自体骨移植组新生骨量最多	2
胶原膜复合含HA的富血小板血浆凝胶^[43]	MSC	1例单侧牙槽嵴裂	无	CT	裂隙处有骨形成,瘘管消失	3
富含血小板的纤维蛋白、自体髂骨^[44]	BMSC	20只比格犬单侧牙槽嵴裂	自体髂骨、自体髂骨复合BMSC、自体髂骨和富含血小板的纤维蛋白	CT、苏木精-伊红染色	实验组骨密度最高,新骨结构形成最好;单纯自体骨移植骨吸收率最高,骨密度最低	6
脱钙骨、硫酸钙人工骨^[45]	MSC	2例单侧牙槽嵴裂	无	CT	骨再生：1例患者34.5%,1例患者25.6%	4
牛胶原脱钙骨基质^[46]	成骨细胞	8例牙槽嵴裂	自体髂骨骨松质	CBCT	裂隙区平均体积和骨化率：实验组（0.55±0.24） cm³、 40.9%,对照组（0.59±0.23） cm³、36.6%	6
HA-CP、Col^[47]	rhBMP-2	大鼠牙槽嵴裂	单纯支架和空白对照	组织学分析、影像学	实验组新骨形成率最高	3
牛骨骨松质^[48]	BMP	63例单侧牙槽突裂	自体髂骨骨松质骨	螺旋CT	治疗总有效率、牙槽骨密度（g·cm^-2）：实验组90%、 0.78±0.19,对照组94%、0.79±0.10,较治疗前显著上升,2组均有尖牙萌出	12
Col^[7]	rhBMP-2	16例单侧牙槽嵴裂	自体髂骨骨松质	CT	术后肿胀、疼痛患者：实验组37.5%,对照组87.5%; 术后平均住院时间（d）、裂隙区骨充填比、平均骨高度（mm）、骨高度百分比：实验组1、74.4%、10.2、 65.0%,对照组3、80.2%、13.9、86.8%	12
Col^[8]	rhBMP-2	18例单侧牙槽嵴裂	自体髂骨骨松质组、骨膜成形术组	CT	平均骨形成率：实验组75%,自体骨移植组78%,骨膜成形术组25.3%,新生骨骨密度实验组与自体骨移植组相似	12

表 4

参考文献 48

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支架材料	优点	缺点
磷酸钙生物陶瓷支架	生物相容性、生物活性、骨传导性好,无免	脆性大,可塑性差,降解性弱,制备时间长,孔隙率难控制,
	疫原性,成本低^[19,20]	产量低
聚合物支架	生物降解性好,生物相容性好,加工灵活,	脆性大,力学强度差,体内强度衰减快,降解不易控制,降解
	可塑性好	产物可能导致炎症
异种骨材料	骨传导性好,一定的骨诱导能力,来源广泛	有一定抗原性
复合材料支架	结合了相应组分的优点	材料间最适比例难控制,制备技术复杂
负载细胞或生长因子支架材料	成血管化和骨诱导性好	制备成本高,因子的剂量及控制其稳定、持续地释放较难

支架材料	实验组	对照组	应用	评价方法	研究结果	随访时间/月	参考文献
磷酸钙生	HA	自体髂骨	23例单侧牙槽嵴	锥形束计算机断层扫	移植成功。HA为100%,	67.82±10.36;	Benlidayi等^[21]
物陶瓷		骨松质	裂	描（cone beam com-	自体骨移植为83.4%;裂	47.33±13.79
				puted tomography,	隙区骨密度差异无统计学
				CBCT）	意义
	β-TCP	无	7例单侧牙槽嵴裂	CBCT	裂隙区骨体积平均百分比	6	De Ruiter等^[22]
					为73%±6%
	β-TCP	对侧自体	10只荷兰奶山羊	micro-CT	缺损处重建的骨质和骨体	6	Janssen等^[23]
		骨移植	双侧牙槽嵴裂		积与自体骨移植侧一致
	BG	无	1例单侧牙槽嵴裂	放射学	修复效果为Bergland Ⅰ级	12	Ezzat等^[24]
聚合物	牛胶原基	无	1例单侧牙槽嵴裂	X线	裂隙区出现成骨,尖牙正	18	Pradel等^[30]
	质				常萌出
异种骨类	复合牛骨	无	15例单侧牙槽突	X线、CT	X线显示有明显新骨形成,	4	徐燕等^[32]
			裂		患者面部外形改善
	脱蛋白牛	自体髂骨	30例牙槽嵴裂	X线、临床观察	2组骨组织变化没有明显	24	Thuaksuban等^[33]
	骨复合自	骨松质			差异,尖牙萌出;术后并
	体骨				发症明显减少。
	脱蛋白无	无	9例单侧牙槽嵴裂	临床观察、放射学	平均骨扩增量5.45 mm,	2	Aly等^[3]
	机牛骨、				修复效果评价Bergland标
	自体下颌				准分级为Ⅰ级占55%、Ⅱ
	体骨				级34%、Ⅲ级1%

支架材料	对照组	应用	评价方法	研究结果	随访时间/月	参考文献
β-TCP/Col	PLLA/PCL支架	54只SD大鼠	CT、组织学分析	新生成骨的体积比：自体骨移植组	4	Ekin等^[9]
	组、自体骨移植	牙槽嵴裂		45.4%、β-TCP/Col组21.5%、PLLA/
	组、空白对照组			PCL组18.2%
HA/Col/自体	自体髂骨骨松质	15例单侧牙	CT	裂隙区骨体积（mL）、术中输血量	12	Takemaru等^[6]
髂骨骨松质		槽嵴裂		（mL）：自体骨移植组0.518±0.303、
				51.5±37.9,支架组0.648±0.120、
				12.4±5.13;术后12个月骨体积没有明
				显差异
磷酸八钙/Col	Col	6只比格犬牙	Micro-CT、X线、	缺损区被新骨充填,新骨由骨密质和	10	Matsui等^[29]
		槽嵴裂	苏木精-伊红染色	骨松质构成,较Col移植组新生骨体积
				更大