Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (8): 1293-1298.doi: 10.12307/2022.238
Previous Articles Next Articles
Wu Bingshuang1, Wang Zhi2, Tang Yi3, Tang Xiaoyu4, Li Qi5
Received:
2021-01-26
Revised:
2021-02-23
Accepted:
2021-06-05
Online:
2022-03-18
Published:
2021-11-02
Contact:
Li Qi, MD, Associate chief physician, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
About author:
Wu Bingshuang, Associate chief physician, Department of Sports Medicine, No. 1 Orthopedics Hospital of Chengdu, Chengdu 610000, Sichuan Province, China
Supported by:
CLC Number:
Wu Bingshuang, Wang Zhi, Tang Yi, Tang Xiaoyu, Li Qi. Anterior cruciate ligament reconstruction: from enthesis to tendon-to-bone healing[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(8): 1293-1298.
Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks
2.1 腱骨止点的发育 由于肌腱/韧带常需提供不同轴向/方向的运动功能,其与骨的交接处常为应力集中点,该处容易损伤。机体运动需要有效地将力量从收缩的肌肉转移到骨骼,肌腱到骨骼之间通过复杂的过渡组织让应力能够以一定梯度由肌腱转移至骨头上,从而使应力集中最小化。这种组织在受伤后难以重建,这或许与该组织的复杂发育相关,目前关于止点的发育学说有多种观点。 其中之一为肌腱/韧带-骨单元学说,既往研究显示,肌腱及其骨附着点的形成始于胚胎发育过程,由侧板而来,在发育过程中,肌腱最终与骨面通过止点连结起来,需要机体内极为复杂的信号通路引导着肌腱沿着一定走形到特定的骨面前。Sox9基因是间充质细胞向软骨细胞分化的关键因子,该基因在软骨形成过程中由软骨祖细胞和软骨细胞持续表达;Scx基因是一种碱性螺旋-环-螺旋转录因子,由腱组织的祖细胞和细胞表达并调节其分化[22]。研究表明骨面粗隆处的止点在发育阶段,祖细胞会同时表达Sox9和Scx,而与原始软骨仅表达Sox9不同,并且这一过程受到转化生长因子β和骨形态发生蛋白信号传导调节。同时,细胞谱系分析也证实了附着单位祖细胞对Sox9和Scx的共表达,表明肌腱插入部位的细胞来源于Sox9阳性谱系。 而分离模型则与上述观点不同,即整个肌腱-骨该单位的肌腱及骨组织都来自一个共同的祖细胞池,这一祖细胞池概念最早见于一项Sox5?/?Sox6?/?双突变小鼠胚胎的研究中[23]。这些祖细胞通过分化形成肌腱或软骨,从而避开了前面提及的引导机制,因为二者都是原位形成的。此外,该学说下细胞具有高水平的可塑性,这是形成极其多样和复杂的肌腱-骨附着形态所必需的。这一模型的重要依据之一是模型中存在一个共同的Scx和Sox9基因阳性祖细胞池,已有研究通过条件性敲除实验表明,Scx基因阳性细胞表达Sox9对于建立肌腱-骨附着至关重要[24]。分离模型的另一观点认为,随着细胞分化为腱细胞或软骨细胞,Scx和Sox9基因阳性祖细胞的共同池应逐渐减少[22]。 Scx和Sox9基因阳性祖细胞库的发现促使着该细胞调节分子机制的研究。条件性敲除实验表明转化生长因子β信号通路调节着骨骼隆突祖细胞[25],然而关于转化生长因子β在骨骼发生中的作用却长期存在争议。最早的研究表明,转化生长因子β可触发软骨形成[26-27],然而有实验通过对动物体内的间充质干细胞转化生长因子β受体进行阻断,却表明对软骨细胞分化和手指关节形成无显著影响[28]。转化生长因子β信号对Scx和Sox9基因阳性祖细胞库的作用表明尽管这一途径调控软骨形成,但其影响仅限于建立肌腱止点软骨侧的次级祖细胞池。 既往研究表明,转化生长因子 β信号传导在四肢肌腱形成中也是必须的。通过基因消融阻断小鼠胚胎四肢的间充质干细胞转化生长因子β Ⅱ受体,或转化生长因子β1和转化生长因子β2,可导致所有肌腱组织完全丧失[29]。此外,还有研究表明转化生长因子β在肢体发育过程中可调控软骨和肌腱的分化[30]。通过上述研究可知,转化生长因子β信号通路通过调节肌腱和骨隆突祖细胞,从而促进肌腱-骨附着单元形成。 有研究表明参与骨隆突形成的另一种分子途径是骨形态发生蛋白4信号传导[22],条件性敲除四肢间充质细胞的骨形态发生蛋白4可阻止骨骼隆突祖细胞向软骨的分化。另一项实验表明,在肌腱-软骨交界处Scx调控下的骨形态发生蛋白4表达诱导骨骼隆突的形成[22]。两项实验均表明,Scx/骨形态发生蛋白4途径在骨骼突出和肌腱-骨附着单位的发育中起主要作用。 关于肌腱附着单位形成的分子途径仍有许多问题有待解决。研究表明骨形态发生蛋白4缺失不一定导致骨骼隆起的缺失,因而其他骨形态发生蛋白可能参与不同阶段止点发育的调控,目前比较有可能的是骨形态发生蛋白2和骨形态发生蛋白7。四肢间充质细胞受体骨形态发生蛋白受体1a表达的缺失可导致肱骨无骨骼隆起,如三角肌粗隆[31]。此外还应考虑骨形态发生蛋白5,因为动物模型骨形态发生蛋白5阴性突变可导致骨骼隆起形成的异常[32]。此外,可能参与肌 腱/韧带止点形成的其他分子是成纤维细胞生长因子,已有研究证明它与骨骼形态发生和肌腱形成有关[33]。肢体间充质细胞成纤维细胞生长因子受体1和成纤维细胞生长因子受体2的失活可导致骨骼畸形。此外,成纤维细胞生长因子信号还可通过在胚胎发生期间诱导肢体中的Scx基因表达参与肌腱发育[34]。 2.2 腱骨止点的矿质化 研究表明肌腱/韧带止点处的矿化类似于生长板,小鼠在出生后不久便可在已成熟的袖套附近出现梯度矿化,在出生后止点成熟的早期阶段,梯度矿化区与发育中的肌腱被尚未被矿化的骨骺软骨区分开来;之后,随着骨骺软骨在出生后前2周内逐渐矿化,该梯度逐渐转移入腱-骨附着单元的发育过渡组织。软骨内矿化的过程可能由印度刺猬信号和甲状旁腺相关蛋白调控,印度刺猬信号由肥大软骨细胞表达,该分子通过结合膜受体刺激增殖的软骨细胞,从而激活七跨膜转导蛋白并刺激甲状旁腺相关蛋白的合成。然后,甲状旁腺相关蛋白表达阻止印度刺猬信号的进一步表达,从而形成负反馈调节,实现对软骨细胞增殖和成熟的良好控制。 多项研究已通过动物模型探索了印度刺猬信号/甲状旁腺相关蛋白信号通路在肌腱-骨止点矿化中的作用。甲状旁腺相关蛋白、印度刺猬信号、Sox9和X型胶原等已被证实在止点形成及矿化中起作用。甲状旁腺相关蛋白在肌腱到骨上的高表达表明,甲状旁腺相关蛋白在骨骼成熟过程中的矿化界面建模中起着重要作用。在生长板中,甲状旁腺相关蛋白维持软骨细胞增殖并抑制其成熟和矿化;与此相对应的是,在表达Scx细胞中,若甲状旁腺相关蛋白发生缺失,则可导致多处止点位置修复受损。并且如果缺乏甲状旁腺相关蛋白,破骨细胞在长骨线性生长过程中随纤维状骨质延伸和/或迁移的能力会受到限制。在这种情况下,韧带会过早地锚定在骨面上,形成过度矿化的粗大结节。甲状旁腺相关蛋白分布于发育中的肌腱/韧带止点处,指导破骨细胞延伸及迁移。 尽管软骨内骨骼(例如椎骨和长骨)的主要骨化中心出现在妊娠期,但骨骼组织的大量矿化直到孕晚期才出现[34]。Ⅰ型胶原蛋白富集的细胞外基质在膜内骨骼中直接矿化,而在软骨内骨中,矿化同时在2个部位开始:软骨素的核心区域内以及沿其周围的骨环。在软骨中,由肥大软骨细胞合成的X型胶原蛋白基质用作矿物质支架,而在骨环中(以及后来在小梁骨中),主要的矿物质支架蛋白是成骨细胞衍生的Ⅰ型胶原蛋白[35]。 2.3 腱骨止点微解剖结构 经典的腱骨止点分为两种类型:直接型止点和间接型止点[36-37],两者的区别在于组织学上是否存在纤维软骨层的过渡。 对于直接型止点而言,从肌腱或韧带过渡到骨组织,存在经典的4层结构:韧带 -非钙化纤维软骨-钙化纤维软骨-骨固有层,非钙化纤维软骨与钙化纤维软骨之间存在一层明显分界线,即潮标(tidemark),人体中大多数骨组织为此种连接方式,如前、后交叉韧带的胫骨止点和股骨止点,冈上肌肌腱在肱骨上的止点等。 间接型止点,是指肌腱或韧带未通过软骨层过渡,直接连接到骨或骨膜上,此类型的止点包括三角肌腱与肱骨的连接,膝关节内侧副韧带在胫骨止点上的腱骨连接[36-37]。 对于两种连接方式之间的区别,至今尚未明确。有研究提示,当运动时肌腱或韧带与骨面的角度变化更大时,更倾向于形成直接型连接。如上所述,属于直接型连接中的肩关节外展时冈上肌肌腱与肱骨形成的角度相较于属于间接型连接类型的三角肌与肱骨之间形成的角度变化范围更大,而膝关节内侧副韧带中其胫骨止点是间接型连接而股骨止点则为直接型连接,这似乎也与膝关节本身的运动学规律有一定的相关性[38]。ROSSETTI等[39]一项发表在 《Nature Material》的研究提示,直接型止点在从腱过渡至腱骨界面的时候,其腱性结构在靠近界面处成 15°扇形散开,且胶原纤维变细。 对于前交叉韧带的前内侧束和后外侧束来说,其前内侧束相对于后外侧束在止点处与骨质纤维交错更紧致[40]。在前交叉韧带的胫骨止点中,非钙化层和钙化层的厚度均在外侧厚度更大,这提示了前交叉韧带在胫骨外侧所受应力相对内侧和后方更强[41];其前内侧束和后外侧束的附着点处也存在差异。一项采用猪前交叉韧带进行的胫骨止点的研究提示,与胫骨平台骨面相比,内侧水泥线(cement line)较平整,外侧则显得不规律;前内侧束相对于后外侧束,肌腱纤维进入骨面时角度更陡,深度更大,与骨面的交界线也更不规律[42]。前交叉韧带股骨止点的最新研究则显示,前交叉韧带的前内侧束在股骨止点的钙化软骨和非钙化软骨均多于后外侧束,与后外侧相比,前外侧分别多了33%的钙化软骨和143%的非钙化软骨,且前内侧束的附着角比后外侧束大6倍[43]。 2.4 微力学与分子分布 前交叉韧带与骨面附着点附近的结构中,其分子分布存在一定的规律性。QU等[44]使用傅里叶变换红外光谱成像研究了前交叉韧带止点处在不同过渡层的物质变化,提示胶原纤维从肌腱到骨含量逐渐增加,排列逐渐从有序变为不规则;蛋白多糖主要在纤维软骨层,而矿物质主要在“非钙化软骨层-骨”的交界处。当前对于腱骨界面的生物标记分子仍然不清楚,ROSSETTI等[39]发现,在肌腱逐渐过渡到骨的大约 100 μm 的宽度,胶原纤维的类型逐步从跟腱实质的Ⅰ型胶原,过渡到靠近腱骨处(约500 μm处)的Ⅱ型胶原,再到骨组织的 Ⅰ型胶原。KUNTZ等[45]通过转录组学和蛋白组学的方法,发现腱骨交界面相对于肌腱和软骨处,其蛋白表达有一定的特异性,如其Ⅱ型胶原α1的表达量相对于肌腱高了100 000倍;通过不同区域的分子表达对比,对后续植入间充质干细胞的支架修复腱骨止点来说起到了另一个标杆性的参考作用;该团队的另一研究提出了一种在保持力学活性下对腱骨界面进行去细胞化的方法:室温下使用 0.5% SDS 加 1% Triton X-100 处理 72 h可有效处理掉 98%的细胞[46]。 附着点的结构特点和分子与蛋白分布,对韧带的生理功能有一定的影响。LUETKEMEYER 等[47]使用一个三维有限元模型模拟前交叉韧带止点并进行力学研究,结果提示前交叉韧带在股骨止点处应变最大,且随着韧带与骨面的附着角(attachment angle)减小而增大;同时韧带与骨面的止点形成的形状越呈现“凹”形则应变越大。该团队的另一个研究进一步对比了前交叉韧带在股骨和胫骨止点的解剖差异,结果显示前交叉韧带在胫骨止点比股骨止点的附着角大3.9倍;在纤维软骨的厚度上,股骨止点的钙化软骨和非钙化软骨比胫骨止点分别厚43%和226%,特别是在非钙化软骨的中部[48]。CHEN等[49]一项对前交叉韧带股骨止点多等级的研究提示,反复低强度的疲劳应力刺激会导致股骨止点的组织改变,影响组织完整性,从而导致非接触性前交叉韧带断裂。 作为一个重要的力学稳定装置,其形态和结构也与发育过程中力学刺激密切相关。SCHLECHT等[50]观察了发育期小鼠接受运动刺激与否是否会对前交叉韧带止点产生相应的改变,结果提示,接受运动刺激的小鼠,相对于无运动刺激的小鼠,其胫骨止点的钙化软骨面积大了20.4%,厚度大了29.2%;运动中前交叉韧带在股骨止点的应力分布,比胫骨止点处变化更大(大小与方向)。SUZUKI等[51]通过对前交叉韧带在股骨侧和胫骨侧纤维软骨和软骨下骨的结构分析进一步验证了该结论,其研究显示,股骨侧非钙化软骨显著比胫骨侧非钙化软骨厚,但钙化软骨则两侧差异不大;骨小梁的排列,在股骨止点的近后侧和胫骨止点前内侧更加有序,这也与前交叉韧带日常应力载荷分布密切相关。 2.5 腱骨愈合面临的挑战 肌腱/韧带与骨组织有完全不同的理化性质,肌腱/韧带有着200 MPa的拉伸/压缩模量,而骨组织的拉伸/压缩模量则高达20 GPa[52],一旦缺少一定的移行区缓冲而将这二者结合固定,这种显著的刚性模量不匹配便可表现为止点处潜在的破坏性应力集中。正常人体内肌腱/韧带到骨组织的复杂过渡区即止点,能有效地将肌 腱/韧带的应力传递到骨组织上,而这是通过宏观层面的外形、微观层面的纤维走形、止点处钙化的空间梯度来实现的。这种复杂的天然结构难以通过外科手术重现,故而依赖于腱骨愈合的如肩袖撕裂修复及前交叉韧带损伤重建后均常因止点愈合不良导致手术失败。 从肌腱到骨面组织成分的梯度变化有助于两种不同性质的物质之间有效地转移应力,然而肌腱/韧带止点的起源和成熟,尤其是纤维软骨层尚不清楚。其次,尚不清楚不同的生长因子、机械负荷和细胞外基质对肌腱/韧带止点愈合的作用。再者,尽管已证明各种生物和生物物理方法可有效改善肌腱/韧带止点愈合,但最佳剂量、时机和潜在机制仍有待进一步研究。对于前交叉韧带重建,尽管采用不同治疗方式改善了肌腱移植到骨隧道的愈合,但重建后韧带的机械性能仍不如正常前交叉韧带;在动物实验中,移植物复合体的力学性能仍低于正常前交叉韧带,极限破坏载荷仅能达到完整韧带-骨复合体的10%-20%,但需要注意的是,除了肌腱-移植物-胫骨复合体外,极限载荷还取决于移植物的中间物质重塑骨隧道愈合。 2.6 临床腱骨愈合 用生物因子加强或促进前交叉韧带重建后的腱骨愈合一直都是研究的热门。目前前交叉韧带重建后,关于促进腱骨愈合的研究主要集中在生长因子、生物材料、干细胞、基因疗法、自体组织等方法,且多数研究集中在术中对腱骨界面进行干预[53-54],其中富血小板血浆和间充质干细胞是较常见的促进因子[55-56]。AGIR等[58]将新西兰大白兔分为2组,其中给予富血小板血浆处理组在术后腱骨愈合效果上显著更佳,并且术后坏死等并发症更少出现。TIAN 等[59]对大鼠的体内研究发现黄芩素可通过激活 Wnt/β-Catenin 通路促进腱骨愈合。HU等[60]提出位于中性粒细胞和巨噬细胞表面的唾液酸样物质(Siglecs)可能具有免疫抑制作用,从而减少前交叉韧带重建后的炎症反应。以上研究提示使用生物因子加强腱骨愈合可能是一种可行的办法,但其机制仍然未清楚,且缺乏更高等级的证据支持其临床应用[53]。 通过改进移植物固定方式或增加物理刺激来促进腱骨愈合,也是研究的方向之一。MUTSUZAKI等[61]一项兔膝关节的生物力学实验对比了使用普通悬吊固定和骨槽(bone socket)固定股骨端移植物后的断裂载荷、移植物刚度、应力强度,两者之间差异无显著性意义,这提示肌腱移植物的固定方法可能不会影响肌腱到骨的愈合,并且与隧道方位无关,而与固定方式相关。SUN等[62]则发现术后若对膝关节进行“负压处理”可有效促进腱骨愈合。也有研究表明,术后进行持续被动活动,其纤维软骨数量、Ⅰ型胶原蛋白等数量显著增加,提示其愈合程度更好[63]。WANG等[64]使用加入镁的界面螺钉进行移植物固定,提出了镁可以通过募集骨髓间充质干细胞而促进腱骨愈合过程。 近年来,在韧带重建方面组织工程也取得了一定的研究进展,许多新的材料也在被尝试用来促进腱骨愈合过程。LI 等[65]在新西兰大白兔上的实验发现柔性双极纳米纤维可通过恢复腱骨间的双层纤维软骨结构,从而有效促进腱骨愈合。TEUSCHL等[66]使用一个基于蚕丝的前交叉韧带支架代替传统的自体或同种异体移植物,观察加入细胞是否会影响其骨整合,发现结果差异无显著性意义,两者均产生了过渡层的纤维层。PARK 等[17]在大白兔前交叉韧带重建术中使用一个3D打印套筒支架并植入间充质干细胞,发现相对于对照组,该方法可有效促进腱骨愈合。 近年来利用组织工程支架进行前交叉韧带的修复成为研究热点,最初的尝试源于利用水凝胶作为组织替代或用作生长因子的载体,因为水凝胶与大多数结缔组织的细胞外基质具有结构相似性[67]。在一项动物实验中,向前交叉韧带损伤兔模型关节内注射透明质酸,12周的组织学评估显示,在实验组中Ⅲ型胶原蛋白增加,血管生成更多,炎症更少,并且总体上修复得到改善[68]。 除透明质酸外,还有组织工程胶原被用作生物支架。一项体外研究使用组织工程化的胶原蛋白支架作用于撕裂前交叉韧带,实验表明,成纤维细胞在植入的胶原蛋白支架内可定植[69]。体内研究中,在尤卡坦小型猪模型上,与仅进行缝合修复相比,在前交叉韧带修复中使用胶原蛋白贴片在修复后韧带的生物力学测试中未能显示出优越性[70];与对照组相比,测试组的组织学评估未显示韧带组织成熟度指数的显著差异。然而,来自同一研究所的另一项研究表明,使用胶原蛋白血小板复合膜片可以改善修复后韧带的生物力学和组织化学特性[71]。"
[1] MARKOLF KL, MENSCH JS, AMSTUTZ HC. Stiffness and laxity of the knee--the contributions of the supporting structures. A quantitative in vitro study. J Bone Joint Surg Am. 1976;58(5):583-594. [2] LEVINE JW, KIAPOUR AM, QUATMAN CE, et al. Clinically relevant injury patterns after an anterior cruciate ligament injury provide insight into injury mechanisms. Am J Sports Med. 2013;41(2):385-395. [3] LAI CCH, ARDERN CL, FELLER JA, et al. Eighty-three per cent of elite athletes return to preinjury sport after anterior cruciate ligament reconstruction: a systematic review with meta-analysis of return to sport rates, graft rupture rates and performance outcomes. Br J Sports Med. 2018;52(2):128-138. [4] AGEL J, ROCKWOOD T, KLOSSNER D. Collegiate ACL Injury Rates Across 15 Sports: National Collegiate Athletic Association Injury Surveillance System Data Update (2004-2005 Through 2012-2013) . Clin J Sport Med. 2016;26(6):518-523. [5] ØIESTAD BE, ENGEBRETSEN L, STORHEIM K, et al. Knee osteoarthritis after anterior cruciate ligament injury: a systematic review. Am J Sports Med. 2009;37(7):1434-1443. [6] LOHMANDER LS, ENGLUND PM, DAHL LL, et al. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007;35(10):1756-1769. [7] MIHELIC R, JURDANA H, JOTANOVIC Z, et al. Long-term results of anterior cruciate ligament reconstruction: a comparison with non-operative treatment with a follow-up of 17-20 years. Int Orthop. 2011;35(7):1093-1097. [8] COX CL, HUSTON LJ, DUNN WR, et al. Are articular cartilage lesions and meniscus tears predictive of IKDC, KOOS, and Marx activity level outcomes after anterior cruciate ligament reconstruction? A 6-year multicenter cohort study. Am J Sports Med. 2014;42(5):1058-1067. [9] OIESTAD BE, HOLM I, AUNE AK, et al. Knee function and prevalence of knee osteoarthritis after anterior cruciate ligament reconstruction: a prospective study with 10 to 15 years of follow-up. Am J Sports Med. 2010;38(11):2201-2210. [10] RISBERG MA, OIESTAD BE, GUNDERSON R, et al. Changes in Knee Osteoarthritis, Symptoms, and Function After Anterior Cruciate Ligament Reconstruction: A 20-Year Prospective Follow-up Study. Am J Sports Med. 2016;44(5):1215-1224. [11] GIOVE TP, MILLER SJ, KENT BE, et al. Non-operative treatment of the torn anterior cruciate ligament. J Bone Joint Surg Am. 1983;65(2): 184-192. [12] MAHAPATRA P, HORRIAT S, ANAND BS. Anterior cruciate ligament repair - past, present and future. J Exp Orthop. 2018;5(1):20. [13] FOSTER TE, WOLFE BL, RYAN S, et al. Does the graft source really matter in the outcome of patients undergoing anterior cruciate ligament reconstruction? An evaluation of autograft versus allograft reconstruction results: a systematic review. Am J Sports Med. 2010; 38(1):189-199. [14] SAMUELSEN BT, WEBSTER KE, JOHNSON NR, et al. Hamstring Autograft versus Patellar Tendon Autograft for ACL Reconstruction: Is There a Difference in Graft Failure Rate? A Meta-analysis of 47,613 Patients. Clin Orthop Relat Res. 2017;475(10):2459-2468. [15] XIE X, LIU X, CHEN Z, et al. A meta-analysis of bone-patellar tendon-bone autograft versus four-strand hamstring tendon autograft for anterior cruciate ligament reconstruction. Knee. 2015;22(2):100-110. [16] MOHTADI N, CHAN D, BARBER R, et al. A Randomized Clinical Trial Comparing Patellar Tendon, Hamstring Tendon, and Double-Bundle ACL Reconstructions: Patient-Reported and Clinical Outcomes at a Minimal 2-Year Follow-up. Clin J Sport Med. 2015;25(4):321-331. [17] PARK SH, CHOI YJ, MOON SW, et al. Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft. Arthroscopy. 2018; 34(1):166-179. [18] LU H, CHEN C, XIE S, et al. Tendon Healing in Bone Tunnel after Human Anterior Cruciate Ligament Reconstruction: A Systematic Review of Histological Results. J Knee Surg. 2019;32(5):454-462. [19] CHEN CH. Graft healing in anterior cruciate ligament reconstruction. Sports Med Arthrosc Rehabil Ther Technol. 2009;1(1): 21. [20] BUEHLER MJ, YUNG YC. Deformation and failure of protein materials in physiologically extreme conditions and disease. Nature Mat. 2009; 8(3):175-188. [21] DENG X H, LEBASCHI A, CAMP CL, et al. Expression of Signaling Molecules Involved in Embryonic Development of the Insertion Site Is Inadequate for Reformation of the Native Enthesis: Evaluation in a Novel Murine ACL Reconstruction Model. J Bone Joint Surg Am. 2018;100(15):e102. [22] BLITZ E, SHARIR A, AKIYAMA H, et al. Tendon-bone attachment unit is formed modularly by a distinct pool of Scx- and Sox9-positive progenitors. Development. 2013;140(13):2680-2690. [23] BRENT AE, BRAUN T, TABIN CJ. Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development. Development. 2005;132(3):515-528. [24] SUGIMOTO Y, TAKIMOTO A, AKIYAMA H, et al. Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament. Development. 2013;140(11):2280-2288. [25] BLITZ E, VIUKOV S, SHARIR A, et al. Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev Cell. 2009;17(6):861-873. [26] KULYK WM, RODGERS BJ, GREER K, et al. Promotion of embryonic chick limb cartilage differentiation by transforming growth factor-β. Dev Biol. 1989;135(2):424-430. [27] CARRINGTON J L, CHEN P, YANAGISHITA M, et al. Osteogenin (bone morphogenetic protein-3) stimulates cartilage formation by chick limb bud cells in vitro. Dev Biol.1991;146(2):406-415. [28] VERRECCHIA F, MAUVIEL A. Transforming growth factor-β signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol. 2002;118(2):211-215. [29] PRYCE BA, WATSON SS, MURCHISON ND, et al. Recruitment and maintenance of tendon progenitors by TGFβ signaling are essential for tendon formation. Development. 2009;136(8):1351-1361. [30] LORDA-DIEZ CI, MONTERO JA, MARTINEZ-CUE C, et al. Transforming growth factors β coordinate cartilage and tendon differentiation in the developing limb mesenchyme. J Biol Chem. 2009;284(43): 29988-29996. [31] OVCHINNIKOV DA, SELEVER J, WANG Y, et al. BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning. Dev Biol. 2006;295(1):103-115. [32] HOSSEINI A, HOGG D. The effects of paralysis on skeletal development in the chick embryo. II. Effects on histogenesis of the tibia. J Anat. 1991; 177:169-178. [33] EDOM-VOVARD F, SCHULER B, BONNIN MA, et al. Fgf4 positively regulates scleraxis and tenascin expression in chick limb tendons. Dev Biol. 2002;247(2):351-366. [34] ROSEN CJ. Primer on the metabolic bone diseases and disorders of mineral metabolism. John Wiley Sons,2009. [35] KARSENTY G, WAGNER EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell. 2002;2(4):389-406. [36] APOSTOLAKOS J, DURANT TJ, DWYER CR, et al. The enthesis: a review of the tendon-to-bone insertion. Muscles Ligaments Tendons J. 2014;4(3): 333-342. [37] BENJAMIN M, TOUMI H, RALPHS JR, et al. Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load. J Anat. 2006;208(4):471-490. [38] THAMBYAH A, LEI Z, BROOM N. Microanatomy of the medial collateral ligament enthesis in the bovine knee. Anat Rec (Hoboken). 2014;297(12):2254-2261. [39] ROSSETTI L, KUNTZ LA, KUNOLD E, et al. The microstructure and micromechanics of the tendon-bone insertion. Nat Mater. 2017;16(6): 664-670. [40] ZHAO L, LEE PVS, ACKLAND DC, et al. Microstructure Variations in the Soft-Hard Tissue Junction of the Human Anterior Cruciate Ligament. Anat Rec (Hoboken). 2017;300(9):1547-1559. [41] DAI C, GUO L, YANG L, et al. Regional fibrocartilage variations in human anterior cruciate ligament tibial insertion: a histological three-dimensional reconstruction. Connect Tissue Res. 2015;56(1):18-24. [42] ZHAO L, THAMBYAH A, BROOM ND. A multi-scale structural study of the porcine anterior cruciate ligament tibial enthesis. J Anat. 2014;224(6): 624-633. [43] BEAULIEU ML, CAREY GE, SCHLECHT SH, et al. On the heterogeneity of the femoral enthesis of the human ACL: microscopic anatomy and clinical implications. J Exp Orthop. 2016;3(1):14. [44] QU D, SUBRAMONY SD, BOSKEY AL, et al. Compositional mapping of the mature anterior cruciate ligament-to-bone insertion. J Orthop Res. 2017;35(11):2513-2523. [45] KUNTZ LA, ROSSETTI L, KUNOLD E, et al. Biomarkers for tissue engineering of the tendon-bone interface. PLoS One. 2018;13(1): e0189668. [46] XU K, KUNTZ LA, FOEHR P, et al. Efficient decellularization for tissue engineering of the tendon-bone interface with preservation of biomechanics. PLoS One. 2017;12(2):e0171577. [47] LUETKEMEYER CM, MARCHI BC, ASHTON-MILLER JA, et al. Femoral entheseal shape and attachment angle as potential risk factors for anterior cruciate ligament injury. J Mech Behav Biomed Mater. 2018;88:313-321. [48] BEAULIEU ML, CAREY GE, SCHLECHT SH, et al. Quantitative comparison of the microscopic anatomy of the human ACL femoral and tibial entheses. J Orthop Res. 2015;33(12):1811-1817. [49] CHEN J, KIM J, SHAO W, et al. An Anterior Cruciate Ligament Failure Mechanism. Am J Sports Med. 2019;47(9):2067-2076. [50] SCHLECHT SH, MARTIN CT, OCHOCKI DN, et al. Morphology of Mouse Anterior Cruciate Ligament-Complex Changes Following Exercise During Pubertal Growth. J Orthop Res. 2019;37(9):1910-1919. [51] SUZUKI D, OTSUBO H, ADACHI T, et al. Functional Adaptation of the Fibrocartilage and Bony Trabeculae at the Attachment Sites of the Anterior Cruciate Ligament. Clin Anat. 2020;33(7):988-996. [52] EINHORN TA, BUCKWALTER JA, O’KEEFE RJ. Orthopaedic basic science: foundations of clinical practice. Amer Acad Orthop. 2007. [53] HEXTER AT, THANGARAJAH T, BLUNN G, et al. Biological augmentation of graft healing in anterior cruciate ligament reconstruction: a systematic review. Bone Joint J. 2018;100-b(3):271-284. [54] HAO ZC, WANG SZ, ZHANG XJ, et al. Stem cell therapy: a promising biological strategy for tendon-bone healing after anterior cruciate ligament reconstruction. Cell Prolif. 2016;49(2):154-162. [55] ZHOU Y, ZHANG J, YANG J, et al. Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface. J Tissue Eng Regen Med. 2017;11(12):3445-3456. [56] ZHANG Y, YU J, ZHANG J, et al. Simvastatin With PRP Promotes Chondrogenesis of Bone Marrow Stem Cells In Vitro and Wounded Rat Achilles Tendon-Bone Interface Healing In Vivo. Am J Sports Med. 2019; 47(3):729-739. [57] MURRAY IR, GEESLIN AG, GOUDIE EB, et al. Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO): Platelet-Rich Plasma and Mesenchymal Stem Cells. J Bone Joint Surg Am. 2017; 99(10):809-819. [58] AGIR I, AYTEKIN MN, KUCUKDURMAZ F, et al. The effect of platelet-rich plasma in bone-tendon integration. Adv Clin Exp Med. 2017;26(2): 193-199. [59] TIAN X, JIANG H, CHEN Y, et al. Baicalein Accelerates Tendon-Bone Healing via Activation of Wnt/beta-Catenin Signaling Pathway in Rats. BioMed Res Int. 2018;2018:3849760. [60] HU J, YAO B, YANG X, et al. The immunosuppressive effect of Siglecs on tendon-bone healing after ACL reconstruction. Med Hypotheses. 2015; 84(1):38-39. [61] MUTSUZAKI H, NAKAJIMA H, NOMURA S, et al. Differences in placement of calcium phosphate-hybridized tendon grafts within the femoral bone tunnel during ACL reconstruction do not influence tendon-to-bone healing. J Orthop Surg Res. 2017;12(1):80. [62] SUN Z, WANG X, LING M, et al. Acceleration of tendon-bone healing of anterior cruciate ligament graft using intermittent negative pressure in rabbits. J Orthop Surg Res. 2017;12(1):60. [63] SONG F, JIANG D, WANG T, et al. Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells. Cell Physiol Biochem. 2017; 41(3):875-889. [64] WANG J, XU J, SONG B, et al. Magnesium (Mg) based interference screws developed for promoting tendon graft incorporation in bone tunnel in rabbits. Acta Biomaterialia. 2017;63:393-410. [65] LI X, CHENG R, SUN Z, et al. Flexible bipolar nanofibrous membranes for improving gradient microstructure in tendon-to-bone healing. Acta Biomaterialia. 2017;61:204-216. [66] TEUSCHL AH, TANGL S, HEIMEL P, et al. Osteointegration of a Novel Silk Fiber-Based ACL Scaffold by Formation of a Ligament-Bone Interface. Am J Sports Med. 2019;47(3):620-627. [67] DRURY JL, MOONEY DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. 2003;24(24):4337-4351. [68] WIIG ME, AMIEL D, VANDEBERG J, et al. The early effect of high molecular weight hyaluronan (hyaluronic acid) on anterior cruciate ligament healing: an experimental study in rabbits. J Orthop Res. 1990;8(3):425-434. [69] BERRY SM, GREEN MH. Hyaluronan: a potential carrier for growth factors for the healing of ligamentous tissues. Wound Repair Regen. 1997;5(1):33-38. [70] FLEMING BC, MAGARIAN EM, HARRISON SL, et al. Collagen scaffold supplementation does not improve the functional properties of the repaired anterior cruciate ligament. J Orthop Res. 2010;28(6):703-709. [71] JOSHI SM, MASTRANGELO AN, MAGARIAN EM, et al. Collagen-platelet composite enhances biomechanical and histologic healing of the porcine anterior cruciate ligament. Am J Sports Med. 2009;37(12): 2401-2410. |
[1] | Wang Jianping, Zhang Xiaohui, Yu Jinwei, Wei Shaoliang, Zhang Xinmin, Xu Xingxin, Qu Haijun. Application of knee joint motion analysis in machanism based on three-dimensional image registration and coordinate transformation [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(在线): 1-5. |
[2] | Shao Yangyang, Zhang Junxia, Jiang Meijiao, Liu Zelong, Gao Kun, Yu Shuhan. Kinematics characteristics of lower limb joints of young men running wearing knee pads [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(6): 832-837. |
[3] | Zhou Jianguo, Liu Shiwei, Yuan Changhong, Bi Shengrong, Yang Guoping, Hu Weiquan, Liu Hui, Qian Rui. Total knee arthroplasty with posterior cruciate ligament retaining prosthesis in the treatment of knee osteoarthritis with knee valgus deformity [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(6): 892-897. |
[4] | Yang Kuangyang, Wang Changbing. MRI evaluation of graft maturity and knee function after anterior cruciate ligament reconstruction with autogenous bone-patellar tendon-bone and quadriceps tendon [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(6): 963-968. |
[5] | Li Jie, Zhang Haitao, Chen Jinlun, Ye Pengcheng, Zhang Hua, Zhou Bengen, Zhao Changqing, Sun Youqiang, Chen Jianfa, Xiang Xiaobing, Zeng Yirong. Anterior cruciate ligament rupture and patellofemoral joint stability before sagittal and axial measurement using MRI [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(6): 969-972. |
[6] | Wei Xing, Liu Shufang, Mao Ning. Roles and values of blood flow restriction training in the rehabilitation of knee joint diseases [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(5): 774-779. |
[7] | Liu Shaohua, Zhou Guanming, Chen Xicong, Xiao Keming, Cai Jian, Liu Xiaofang. Changes in kinematic parameters after unicompartmental knee arthroplasty and high tibial osteotomy [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(3): 390-396. |
[8] | Cao Fuyang, Xu Jianzhong, Lu Shitao, Tan Jun, Jiang Xu, Yang Meng, Shi Jianming, Chang Yingjian. Autologous, mixed and ligament advanced reinforcement system ligaments reconstruction of anterior cruciate ligament: evaluation of bone tunnel enlargement value, ligament growth factor and knee function [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(21): 3281-3290. |
[9] | Zhang Xuepu, Wu Yuexin, Zhao Haosen, Ban Zhaoliang, Ma Xiaohu, Tong Gang, Yang Limin. A circular RNA, circ_0040646, regulates the proliferation, differentiation, and apoptosis of knee osteoarthritis chondrocytes by targeted inhibition of microRNA-188-3p [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(20): 3141-3146. |
[10] | Diao Yulei, Zong Xiaorui, Deng Zhibo, Shu Han. Analgesic effect of adductor canal block versus femoral nerve block after autogenous bone-tendon-bone reconstruction of the anterior cruciate ligament: an updated Meta-analysis [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(2): 315-320. |
[11] | Yuan Haoxiang, Xu Jing, Zeng Jinshu, Chen Hao, Yan Yelei, Chen Jiahao, Liu Qingshan, Xu Fei. Sequence of prevention for anterior cruciate ligament injury: screening, intervention and assessment [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(17): 2775-2781. |
[12] | Liao Xinyu, He Lu, Li Yanlin, Wang Fuke, Zhou Xiaoxiang, Wang Xu, Zhong Ruiying, Wang Guoliang. Single-bundle anatomical reconstruction of the anterior cruciate ligament with residual ligament stump is beneficial to the recovery of proprioception [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(17): 2631-2635. |
[13] | Xia Peige, Yin Li, Wang Haitao, Zhang Yi, Qiao Renqiu, Kong Zhiheng, Zhao Hongbo, Shi Xiangyu. Effect of knee ligamentous laxity on patient satisfaction after total knee arthroplasty: a medium to long-term follow-up [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(15): 2323-2329. |
[14] | Zhao Chi, Xu Hui, Kang Bingxin, A Xinyu, Xie Jun, Sun Songtao, Shen Jun, Xiao Lianbo, Shi Qi. Tuina prevents deep venous thrombosis of the lower limbs after total knee arthroplasty [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(15): 2330-2336. |
[15] | Zhang Wei, Liu Yunpeng, Wang Xingliang, Peng Chao, Hua Guojun. Imaging analysis of risk factors for knee anterior cruciate ligament injury [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(15): 2361-2366. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||