Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (22): 3586-3591.doi: 10.12307/2022.289
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Tian Chong, Gao Bo, Yu Hongwei, Wang Pei
Received:
2020-11-11
Revised:
2021-02-05
Accepted:
2021-06-10
Online:
2022-08-08
Published:
2022-01-13
Contact:
Wang Pei, Master, Chief physician, Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China
About author:
Tian Chong, Master candidate, Department of Hand and Foot Surgery, Affiliated Hospital of Chengde Medical College, Chengde 067000, Hebei Province, China
CLC Number:
Tian Chong, Gao Bo, Yu Hongwei, Wang Pei. Theoretical research and technical application of bone repair materials in the treatment of calcaneal fractures[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(22): 3586-3591.
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2.1 自体骨 自体骨是临床修复骨缺损的首选材料。李笛等[6]对比植入自体髂骨和同种异体骨的区别,发现自体髂骨组的切口干燥时间、切口愈合时间及术后24 h引流量均少于同种异体骨组,同时同种异体骨组还有4例患者出现皮肤坏死。张俊杰等[7]的研究则发现,自体骨组与同种异体骨组均能减轻患者术后疼痛,恢复跟骨高度和足部功能,在疗效上并无明显差异。张柏等[8]的研究发现,自体髂骨移植组切口并发症的发生率与同种异体骨移植组有明显差异,自体髂骨移植组能减少切口相关并发症的发生。因此,多数的作者仍然认为自体骨是植骨的“金标准”。 2.2 同种异体骨 同种异体骨是来源于他人捐赠并消毒灭菌后的新鲜骨组织。章芃等[9]对32例跟骨关节内骨折患者应用钢板内固定加同种异体骨联合持续高负压引流治疗,所有患者均获得随访,随访时间为2-50个月,术后X射线平片显示跟骨骨折均获得骨性愈合,未发生排异反应,患者跟骨活动后无疼痛,优良率达97%。马延辉等[10]通过对比单纯应用钛板固定跟骨和钛板内固定联合同种异体骨植骨治疗跟骨骨折的疗效发现,联合同种异体骨治疗后的术后并发症发生率低、负重后疼痛发生率低,能明显改善患者Maryland评分。荣向科等[11]在急诊手术下对18例患者应用钛板联合同种异体骨治疗,所有患者术后X射线片显示骨折获得解剖复位,随访6-18个月骨折均达到一期愈合,未出现过敏反应及排异反应,优良率为85.7%。郑海峰等[12]研究发现在术后1年时,钢板内固定联合同种异体骨治疗组的Bohler角、Gissane角及跟骨高度均优于单纯钢板内固定治疗组,能更好地恢复跟骨的解剖形态和改善足部功能。因此,同种异体骨在一定程度上解决自体骨的取骨区不适、骨量有限等不足,但由于其来源于他人组织,在生物力学强度和来自供者的潜在疾病传播风险方面也存在局限性。 2.3 硫酸钙 硫酸钙又称熟石膏,粉末型的硫酸钙人工骨可注射给药,使手术操作难度降低。章明刚[13]对比硫酸钙人工骨和自体骨治疗跟骨骨折的疗效发现,硫酸钙人工骨组的手术时间和术中出血量明显少于自体骨组,两组术后切口干燥时间、拆线时间、术后并发症和换组功能恢复情况均无明显差异。王华等[14]对12例跟骨骨折患者采用硫酸钙人工骨植骨及接骨板置入内固定进行治疗,进行了7-18个月随访,X射线片显示所有骨折达解剖复位,骨折均达到一期愈合,骨折平均愈合时间为12周,根据Maryland 足部评分系统,总优良率为92%,所有患者均未出现排斥反应、过敏反应及毒性反应。苏冠龙等[15]对35例患者跟骨骨折进行锁定钢板联合硫酸钙人工骨治疗,全部患者获得随访,随访时间8-30个月,术后X射线片显示所有骨折均获得骨性愈合,优良率为89.7%,所有患者均未出现切口感染、皮瓣坏死、钢板外露或断裂等并发症。王波等[16]应用硫酸钙人工骨植骨治疗41例根骨骨折患者,有3例出现切口延迟愈合,1例出现钢板断裂,4例出现术后关节面再次塌陷。硫酸钙的吸收速度有可能超出新生骨组织的形成速度,使得其作为支撑物的作用有限。 2.4 磷酸钙 海洋珊瑚为天然硫酸钙的来源,具有良好的生物相容性和空间三维结构。罗亚平等[17]通过自固化磷酸钙人工骨植骨结合钢板内固定治疗跟骨骨折,对81例患者进行随访,随访时间为10-19 个月,所有患者骨折全部愈合,优良率为94.0%,期间所有患者未出现感染、过敏等并发症。周敏[18]的研究发现,新型可注射磷酸钙骨水泥联合空心螺钉内固定可以减少术后并发症的发生,且术后足功能恢复良好,患者预后良好。许文斌等[19]对比了自固化磷酸钙人工骨与异体骨治疗跟骨骨折的区别,发现两者作为植骨材料应用于跟骨骨折的治疗效果相当,无明显差异,但磷酸钙人工骨无排异反应,可减少相关并发症的发生。磷酸钙的降解过程缓慢且存在着脆性大、柔韧性不足等缺点,限制了其在临床的应用。 2.5 羟基磷灰石 羟基磷灰石具有与人体骨组织相似的化学成分和空间结构。王大平等[20]对27例骨缺损患者应用羟基磷灰石治疗,并进行了11-26个月的随访,术后X射线片显示了羟基磷灰石和正常骨骼之间的界限,在13-16个月内界限开始变得模糊,所有患者均达到一期愈合,没有并发症发生。HIRAO等[21]对6例患有类风湿足的患者进行羟基磷灰石植入治疗,术后患者均无切口不适症状,在负重行走后融合部位无疼痛,所有患者在6-10周完成骨愈合,在12个月内所有的羟基磷灰石均被吸收,跟骨骨缺损得到恢复。同时研究还指出,如果术前不能控制类风湿疾病的进程,可能会出现骨愈合的失败,因为所移植的羟基磷灰石可能会在骨愈合之前就被活化的破骨细胞所破坏。由于类固醇对成骨细胞有抑制作用,因此还要限制类固醇类药物的使用。羟基磷灰石人工骨存在力学性能差、抗压和抗折性能差等缺点,只能用于非承重骨的缺损修复。 2.6 脱钙骨基质 脱钙骨基质为在制备同种异体骨时尽可能地保留胶原基质和生长因子。GALLI等[22]评估了12例内踝截骨术结合脱钙骨基质软骨下骨移植的疗效,疼痛评分在6-24个月呈现减少趋势,同时致残率也显著降低。在治疗运动员急性第五跖骨近端骨折中,LAREAU等[23]的研究表明,脱钙骨基质联合髓内螺钉固定可以使运动员能早期返回赛场,平均时间为8.7周;MITCHELL等[24]的研究表明,脱钙骨基质联合钢板内固定可达到同样的结果,重返赛场的时间是12.3周。由于脱钙骨基质的制备需要灭菌、脱矿等处理,因此在生物力学强度和疾病传播的方面存在风险。 2.7 复合材料 2.7.1 富血小板血浆 富血小板血浆是通过离心技术所提取的血小板悬液,富含各种促进骨愈合的生长因子。GANDHI等[25]对足踝骨折术后并发骨不连的患者应用富血小板血浆治疗,平均愈合时间为60 d,且所有骨折均达到一期愈合,同时还发现骨不连患者血液中的血小板衍生生长因子及转化生长因子β浓度均较新鲜骨折明显降低。在BIBBO等[26]的研究中,有62例患者进行富血小板血浆治疗,术后每2周进行X射线片检查,随访时间为6个月,发现在术后平均41 d时有94%的患者达到骨愈合。GALLI等[22]对比了在踝关节置换时应用富血小板血浆和自体骨移植治疗对下胫腓联合融合率的影响,使用富血小板血浆治疗的患者术后8周时的下胫腓联合融合改善率为61.4%,12周时融合改善率为73.6%;而联合使用富血小板血浆及自体骨移植组的患者,术后8周时的下胫腓联合融合改善率为76%,12周时融合改善率为93.9%。尽管富血小板血浆被广泛用于治疗各种骨组织问题,但确切的生物成分及其对骨愈合的影响仍然有待发现。 2.7.2 骨形态发生蛋白 骨形态发生蛋白具有强大的骨诱导潜能和成骨特性。在踝关节融合术中,BIBBO等[27]的研究显示,69例行踝关节融合术的患者接受了重组人骨形态发生蛋白2的辅助治疗,平均融合时间为11周,愈合率为96%,只有3例患者出现伤口并发症。KANAKARIS等[28]的研究在19例融合手术中使用了重组人骨形态发生蛋白7,所有患者的主观疗效为优良,平均临床愈合时间为3.4个月,总体治愈率为90%。但其不能形成骨的三维结构,因此常联合其他骨修复材料使用。 2.7.3 骨髓抽吸浓缩液 骨髓抽吸浓缩液是富含各种骨细胞和生长因子的生物浓缩液。GIANAKOS等[29]回顾了35项关于动物模型中长骨愈合的文献,发现骨髓抽吸浓缩液组的骨愈合情况明显优于对照组。HERNIGOU等[30]的研究显示在60例骨不连患者中,有53例通过经皮注射骨髓抽吸浓缩液的患者达到骨性愈合;同时,有7例愈合较慢患者的骨髓抽吸浓缩液浓度比其他人低,进一步证实了细胞浓度越高结果越好的理论。ADAMS等[31]通过经皮空心螺钉联合骨髓抽吸浓缩液治疗应力性骨折,术后CT证实骨折愈合良好。对糖尿病合并踝部骨折骨不连的研究中,接受骨髓抽吸浓缩液治疗患者比接受髂骨植骨患者的愈合率高[32]。由于目前尚无骨髓抽吸和移植的标准化技术,所以如何以最大限度地提高疗效和减少临床并发症,包括抽吸的位置、危险的神经血管结构、注射器的大小、从每个区域抽出的量以及抽吸浓缩液成分的鉴定,这些都是在临床应用中需要考虑的问题。 2.7.4 血小板衍生生长因子 血小板衍生生长因子可促进软骨内成骨。在对大鼠胫骨骨折局部应用血小板衍生生长因子的研究发现,血小板衍生生长因子治疗组在所有时间点(3,7和10 d)都比对照组有明显改善,骨折处骨痂增生迅速且牢固[33]。DIGIOVANNI等[34]的研究显示在需要后足或踝关节固定术的患者中,与自体骨移植相比,重组人血小板衍生生长因子联合β-磷酸三钙的治疗可有更高的融合率,更好地减轻患者的痛苦且并发症更少。但其作为骨修复材料仍需要更加完善的临床试验。 2.7.5 甲状旁腺激素 甲状旁腺激素可调节钙与磷酸盐的代谢,从而介导骨形成和骨吸收。动物研究表明,重组人甲状旁腺激素对骨折愈合具有积极作用,具有改善的骨密度、促进骨折愈合并增加骨质强度[35-36]。ZHANG等[36]的最新动物研究表明,以低频率(如每周给予一次)重组人甲状旁腺激素治疗,发现骨量和骨骼微结构得到了改善,促进了骨质的愈合。ALMIROL等[37]发现与对照组相比,每日注射20 mg 重组人甲状旁腺激素患者的骨折愈合时间明显缩短,同时骨形成生物标志物显着增加。在关于重组人甲状旁腺激素对肌腱到骨愈合影响的动物研究中,HETTRICH等[38]发现与对照组相比,经重组人甲状旁腺激素治疗的大鼠会促进更多的纤维软骨、成骨细胞和血管的生成。但长期应用甲状旁腺激素有诱发骨肉瘤的可能,需要严格监测患者病情变化。 骨修复材料治疗跟骨骨折的相关临床应用,见表1。"
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