综述
前交叉韧带修补的临床应用现状
中华医学杂志, 2024,104(17) : 1534-1539. DOI: 10.3760/cma.j.cn112137-20231101-00960
摘要

前交叉韧带(ACL)撕裂是常见的运动相关性损伤。关节镜下ACL重建是现阶段手术治疗的金标准,然而该方式仍然存在取腱部位并发症、术后康复时间长等无法解决的问题。ACL修补新技术基于组织愈合目标,能够保留自体韧带组织的本体感受器,保护患膝天然的生物力学特性。目前已有诸多研究探讨ACL修补手术对于特定适应证患者的临床应用可行性和实用性。本文回顾整理了现有国内外的相关研究,重点梳理了ACL修补的机制认知转变、临床应用现状和适应证局限性,ACL修补的研究将促进损伤ACL组织愈合机制的阐明。

引用本文: 夏天, 华英汇. 前交叉韧带修补的临床应用现状 [J] . 中华医学杂志, 2024, 104(17) : 1534-1539. DOI: 10.3760/cma.j.cn112137-20231101-00960.
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前交叉韧带(ACL)撕裂是常见的运动相关性损伤,不论患者是否从事运动相关工作,损伤导致的膝关节不稳都会严重影响患者生活质量。不适当的治疗更是可能导致膝关节不稳发展为创伤性关节炎乃至关节僵硬。而ACL撕裂的治疗也是运动医学研究的重点话题。当前,关节镜下ACL重建手术是手术治疗的金标准,然而近十余年对于ACL损伤组织再生的重新深入认识,使得一度被取代的ACL修补手术再度回到医师视野中。本文将对ACL修补的认知转变过程和临床应用现状进行综述,综合评价该技术的发展前景。

一、ACL修补的认知转变
(一)ACL修补的阻碍因素

20世纪70至80年代的ACL损伤主流手术治疗方式为开放式ACL修补术,其术后2年的短期临床结果良好,能够有效消除患膝轴移,减轻患者膝关节不稳的体感1, 2,然而3.5年的中期随访结果提示,患者术后移植物再断裂率达36%,5年随访再断裂率高达50%3, 4。ACL修补的宗旨在于使撕裂的韧带组织重新愈合5。然而,由于作为膝关节的腔内结构,ACL难以自然形成稳定的纤维蛋白-血小板凝块6, 7,加之滑液会抑制成纤维细胞的ACL修复作用8,造成炎症细胞的迁移和组织重塑都停留在愈合过程中的炎症期或细胞增殖期7。因此,临床医师一度认为损伤的ACL组织是无法愈合的,这使得ACL重建手术从20世纪90年代起逐渐成为主流术式9, 10, 11

(二)ACL组织的可愈合性

事物的发展常是螺旋式上升的,尽管损伤的ACL不具有自然的愈合条件,但随着近年来组织工程技术和关节镜技术的发展,通过人为筛选和干预,损伤的ACL能够获得一个具有生物活性、符合生物力学需求的愈合微环境。近十年来,大量ACL修补的动物在体实验和离体生物力学实验证明,包括生物制剂刺激技术和机械稳定增强技术的ACL修补辅助新技术,可促进ACL组织愈合,显著改善膝关节不稳。改善ACL生物愈合环境的技术包括胶原-血小板混合物、生物活性支架等;改善ACL机械愈合环境的技术包括增强修补、动态稳定修补等,相关研究表明使用新技术的ACL修补临床疗效非劣于ACL重建12, 13, 14, 15, 16, 17,甚至在软骨保护和避免局部炎症方面,ACL修补存在显著优势18, 19。Nguyen等20在山羊的ACL撕裂模型中使用了小肠黏膜下层联合的ACL修补,发现ACL周围纤维滑膜层得到再生,胶原纤维排列紧密,细胞外基质少见空洞和脂肪空泡,胶原纤维间可见新生血管走行,这些特征与自发愈合的内侧副韧带组织学特征相似。上述研究结果证明了ACL修补手术重返临床实践的可能性。

(三)ACL修补的独特价值

尽管ACL重建是目前ACL损伤后手术治疗的金标准,但仍存在无法解决的问题。例如取自体腘绳肌腱时可能出现的隐神经损伤、腘绳肌力减弱,取髌腱时可能出现的髌前区疼痛,相较保守治疗创伤性关节炎风险提高了4.7倍,以及平均长达3个月的术后康复治疗等21, 22, 23

关节镜下ACL修补的运用可一定程度上弥补这些缺陷。Denti等24认为ACL修补手术创伤小,且保留了自体韧带组织的本体感受器,提高了患者膝关节动态平衡的能力,大幅度缩短了术后康复所需的时间,保证了患者的快速返工返岗、重返运动,降低了社会经济负担。此外,ACL修补能够保留韧带止点原生的复杂纤维软骨层过渡结构,具有更强的腱-骨愈合潜力,保护了膝关节的生物力学特性,使得ACL修补能够术后短期减轻患者的疼痛体验25,术后长期降低创伤性关节炎的发病率26,同时ACL修补也降低了再断裂翻修手术的难度27, 28。因此,ACL修补这一技术存在巨大的临床需求和应用价值。

二、ACL修补的临床应用
(一)ACL修补的适应证

为了保证ACL修补后的组织能够获得高质量的愈合,应严格规范手术的适应证。与传统Sherman分型方式不同,van der List等29提出了影像医师读片与临床医师镜下观察一致性更强的ACL撕裂分型方式。该方式按ACL撕裂位置划分为5种类型(图1):Ⅰ型撕裂为股骨近端的直接撕脱,远端ACL组织剩余>90%,Ⅱ型撕裂为远端组织剩余75%~90%,Ⅲ型撕裂为远端组织剩余25%~75%,Ⅳ型撕裂为远端组织剩余10%~25%,Ⅴ型撕裂为胫骨远端的直接撕脱,远端组织剩余<10%,撕裂率分别为Ⅰ型16%,Ⅱ型27%,Ⅲ型52%,Ⅳ型1%,Ⅴ型3%。由于ACL血供来源于其滑膜鞘下的树状分支血管网30,因此撕裂位置更靠近血管网主干膝中动脉,且滑膜鞘完整的Ⅰ型、Ⅱ型撕裂具有最好的愈合潜力,相较之下中段损伤的Ⅲ型撕裂愈合能力则差强人意31, 32, 33。术前MRI所提示的撕裂位置和组织质量可有效预测关节镜下ACL修补的可行性,指导临床医师在术前评估患者是否适应进行ACL修补32。然而,手术探查仍是确定撕裂类型的金标准。

点击查看大图
图1
前交叉韧带(ACL)撕裂位置的MRI分型示意图(自绘,箭头示)A~E:依次为Ⅰ至Ⅴ型撕裂
点击查看大图
图1
前交叉韧带(ACL)撕裂位置的MRI分型示意图(自绘,箭头示)A~E:依次为Ⅰ至Ⅴ型撕裂

临床研究表明25岁以上、病程为急性期(撕裂发生3周以内)、单束ACL股骨端撕脱的年轻患者,通常具有优异的ACL残余组织质量,是目前被广泛接受的ACL撕裂修补适应证34。然而,ACL中段撕裂的老年患者则易发生残余韧带组织的萎缩,进而失去ACL修补的机会35, 36, 37。更完善的生物桥接修补(BEAR)技术有望将ACL修补适应证拓展至中段位置的撕裂38。值得注意的是,青少年手术失败率高达37%,这可能与青少年运动量更大和重返运动时间更短有关39

(二)ACL修补辅助新技术

1.带线锚钉固定修补(SAPR):DiFelice等40于2015年提出了SAPR技术,该技术使用Bunnell缝合法将ACL胫骨段重新捆扎编织,牵拉至ACL前内侧束和后外侧束的撕脱端,在前内侧和后外侧股骨止点位置用带线锚钉固定(图2)。该技术为ACL愈合提供了简易固定的机械环境。

点击查看大图
图2
带线锚钉固定修补示意图(自绘)
图3
内支撑修补示意图(自绘)
图4
动态韧带内稳定修补示意图(自绘)
图5
生物桥接修补示意图(自绘)
点击查看大图
图2
带线锚钉固定修补示意图(自绘)
图3
内支撑修补示意图(自绘)
图4
动态韧带内稳定修补示意图(自绘)
图5
生物桥接修补示意图(自绘)

SAPR技术是ACL修补新技术中最为便捷的一种,不增加额外的加固装置,Ⅰ型撕裂的ACL能够在消除关节滑液影响后愈合,且愈合潜力与内侧副韧带相当41。DiFelice等40对11例患者进行了平均3.5年的随访,其中10例获得了良好的主观和临床结果,包括Lysholm评分、Tegner评分、国际膝关节文献委员会(IKDC)评分、双侧KT-1000测量差值40,在后续平均6年的中期随访中,这组患者维持了良好的临床结果42。Achtnich等43对41例患者开展了SAPR与重建的对照研究,随访28个月的结果显示ACL修补能够达到与重建相当的KT-1000测量值和IKDC评分。其他小型病例系列研究也显示对于严格挑选的ACLⅠ型撕裂和组织质量良好的患者,SAPR技术能够获得良好的短至中期随访结果44, 45, 46

2.内支撑修补(IBLA):Heitmann等47于2014年提出了IBLA技术并开展了猪的生物力学实验。该技术环结捆扎剩余ACL组织,将捆扎线从股骨止点位置的骨道牵出,贴合ACL股骨端和胫骨端撕裂部位,之后沿ACL自其股骨止点至胫骨止点,添加一根穿过膝关节的聚乙烯线带桥接起两端组织(图3)。该技术为愈合期的ACL组织提供了稳定的机械性二次加固。

IBLA技术是目前临床报道最广泛、准确的ACL修补新技术,其手术成功率和膝关节功能改善效果都相当可观48。Heusdens等49对42例患者进行了平均2年的随访,此病例系列研究表明,对于严格符合适应证的急性ACL近端撕裂患者,IBLA能够在术后3个月就展现出对比术前显著改善的膝关节损伤与骨关节炎评分(KOOS)、疼痛视觉模拟评分、Marx活动水平评分等患者报告结局指标。有研究发现,IBLA能够有效保留患者膝关节本体感觉,有助于预防创伤性关节炎的发生,也能让职业运动员在术后快速恢复到满负荷的训练状态50, 51。一项系统性综述表明,与ACL重建相比,IBLA在Lysholm评分、IKDC评分、双侧松弛度差值、轴移分级或移植物断裂率方面差异无统计学意义,其中4篇病例系列报道提示IBLA可依靠其更优秀的韧带愈合速度和生物力学特性在中长期随访中保持良好的临床结果52。IBLA术后的总体ACL再断裂率约为8%,尽管各年龄段手术成功的患者都获得了良好的功能改善,但其中青少年患者手术失败率相对更高(约17%),因此应谨慎对未成年的高运动水平患者行IBLA术53, 54

3.动态韧带内稳定修补(DIS):Kohl等15于2013年提出了DIS技术并开展了动物实验。该技术使用聚乙烯线带桥接起ACL两侧的断端,近端通过股骨骨道固定,远端连接胫骨骨道内的80 N预加载弹簧装置进行机械性增强(图4)。该技术独特的弹簧装置在植入后对胫骨近端持续施加向后拉力,为损伤组织的愈合提供了一个主动的机械性保护。

未成年的高运动水平患者同样是DIS技术潜在的失败风险因素36。Hoogeslag等55对48例患者开展了DIS与ACL重建的对照研究,随访2年的结果显示DIS技术具有非劣于重建的IKDC评分和再断裂率。Schliemann等56对60例患者开展了DIS与ACL重建的对照研究,随访1年发现接受DIS治疗的患者在术后2~3周活动量显著恢复,且DIS组与重建组患者膝关节力学参数和胫骨前移距离差异无统计学意义。一项数据库分析表明,DIS技术与ACL重建的二次关节镜检查率和手术翻修率差异均无统计学意义,且DIS技术能够让患者提前1个月回归工作岗位57。然而,DIS术后患者常因ACL再断裂翻修手术以外的原因接受额外手术,其中占大多数的是局部麻醉下的DIS装置移除手术58。相关临床研究发现DIS术后6个月起,ACL组织即可愈合承担稳定功能,此时可选择移除胫骨内的DIS装置,且装置移除不影响术后2年随访中患者的膝关节稳定度及功能评分59,加之装置引起的胫骨近端局部不适感,高达50%的患者选择术后半年适时移除DIS装置58

4.BEAR技术:Murray等60于2016年提出了BEAR技术。该技术针对损伤的ACL组织缺乏血供及过早丢失未成熟纤维蛋白-血小板凝块的问题,在缝合修补的基础上使用了生物制剂胶原支架桥接断端,为ACL愈合提供了适宜的生物微环境(图5)。目前较为成熟的BEAR技术通常使用由患者全血浸染的胶原仿生细胞外基质支架桥接断端,仍在实验室及临床应用起步阶段的生物制剂包括细胞因子、富血小板血浆、干细胞等61, 62, 63, 64, 65, 66, 67

由于BEAR技术使用生物制剂的伦理因素,目前相关临床研究数量较少,但就现有结果而言,该技术已经展现出了优秀的ACL撕裂治疗潜力。Murray等68对100例患者开展了首例随机对照临床试验,将患者随机分为BEAR组和ACL重建组,随访2年揭盲结果显示BEAR技术能够达到非劣于重建的IKDC评分和双侧膝关节前后松弛度差值,而其平均腘绳肌肌力显著高于重建组,且在未成年的高运动水平患者中也获得了相当的治疗效果。BEAR技术也展现出了拓展ACL修补适应证至Ⅳ型撕裂的潜力38

三、ACL修补的局限性

尽管目前ACL修补在新技术的支持下,临床研究初期结果令人满意,但其距离成为临床医师的可选手术方案仍然存在相当的限制。首先,ACL修补对于患者的残余韧带组织质量有着严格的筛选标准,这大幅限制了手术的适应证,使得大量中老年、运动要求高、ACL中段撕裂或伤后超过1个月的患者无法通过ACL修补获得令人满意的手术效果。其次,运动医学手术治疗的成功离不开术后康复的功劳。目前,仍然缺乏适用于ACL修补的规范理疗和重返运动方案,激进的康复方案可能导致韧带无法愈合,而保守的方案则可能导致韧带应力不足而萎缩,这都有可能造成ACL修补的失败。

综上,近十余年来,ACL修补的实验室及临床研究逐渐改变了早期临床医师对于ACL愈合可能性的认知,再次将该手术方案引入临床医师的视野。目前,许多研究显示ACL修补在治疗急性病程、股骨端撕脱以及韧带残余组织质量良好的特定适应证患者中,治疗潜力与ACL重建相当,但仍然缺乏高质量的大型随机对照临床试验,以反映ACL修补的长期临床结果。同时,ACL修补狭窄的适应证和康复方案的缺乏限制了该手术方案在临床医师中的推广,各种辅助新技术的复杂创新设计与临床手术技术的普适性之间也存在一定的矛盾。随着ACL修补相关研究的加速推进,损伤ACL的愈合机制终将被阐明,为现有ACL修补手术的优化或新型ACL修补技术的开发提供理论指导。

引用本文:

夏天, 华英汇. 前交叉韧带修补的临床应用现状[J]. 中华医学杂志, 2024, 104(17): 1534-1539. DOI: 10.3760/cma.j.cn112137-20231101-00960.

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