腱-骨结合部结构化界面修复的研究进展

在运动系统中,腱-骨结合部在运动过程中起到抗拉伸、承载负荷的作用,因此其愈合效果在恢复关节功能方面起到至关重要的作用。腱-骨界面损伤修复过程多为瘢痕组织形成,从形态结构和生物力学强度方面难以达到理想效果。而组织工程方法能够从种子细胞、生长因子、支架材料三方面来促进腱-骨愈合效果,是腱-骨愈合发展领域的新方向。     

促进肩袖止点腱骨愈合的研究进展

肩袖修补术是肩袖撕裂常用的治疗方式,能有效缓解肩关节疼痛,改善肩关节的活动,但肩袖修补术后肩袖再撕裂的发生率依然很高,主要原因在于肩袖修补术后肩袖止点处腱—骨愈合差,不能恢复原有的组织学结构和生物力学性能。因此,如何有效提高肩袖止点处腱骨愈合是解决此类问题的关键。目前随着人们对于肩袖止点研究的不断深入,各类治疗方法在改善肩袖止点腱骨愈合方面取得了较大的进展。本文将从影响肩袖止点处腱骨愈合的因素、肩袖止点处腱骨界面的恢复以利于肩袖腱骨愈合以及组织工程学在腱骨愈合中的应用3个方面阐述近几年关于肩袖腱骨愈合的研究进展,以期为肩袖撕裂的临床治疗提供一定的指导。     

肩袖修复后促进腱骨界面软骨再生的研究进展

肩袖损伤是造成肩关节功能障碍最常见的原因,尽管手术技术不断进步,但肩袖修复术后再撕裂发生率依然高达20%~94%。从组织病理学角度看,传统肩袖重建术后正常腱骨界面组织结构无法重演,主要问题是肌腱插入骨部位的软骨过渡层不能再生,腱骨之间仅为瘢痕愈合,有研究证实修复后肩袖止点的抗拉强度大幅减弱,推测这可能是已修复肩袖容易发生再撕裂的原因之一。近年来,越来越多的国内外研究致力于利用生物学技术促进肩袖修复后腱骨界面软骨再生,尝试恢复正常腱骨连接部的组织形态,已成为目前研究的热点。本文就这方面的基础研究进展作一综述。     

前交叉韧带重建术后腱-骨和骨-骨界面愈合的比较研究

目的 探讨并比较两种移植物重建前交叉韧带(anterior cruciate ligament,ACL)后早期移植物隧道界面愈合的生物学机制. 方法 55只成年新西兰大白兔,体重2.0～2.8 kg.左膝关节切取带胫骨.骨块的髌韧带作为供区,右膝关节作为自体移植重建ACL受区.移植物骨块端为骨.骨界面愈合模型,韧带端为腱.骨界面愈合模型.术后观察实验动物一般情况,术后第2、4和8周取材(n=5)行大体及组织学观察,并于第4、8周取材(n=20)进行生物力学检测. 结果 术后动物肢体活动情况良好,实验过程中ACL连续性完整,张力适中.组织学观察:术后2周骨.骨界面大部分区域为纤维组织连接,腱一骨界面主要为肉芽组织填充;术后4周骨.骨界面大部分区域骨性愈合,腱.骨界面可见成骨反应及大量成纤维细胞;术后8周骨.骨界面已完全骨性愈合,腱.骨界面部分区域可见Sharpey纤维,形成间接止点.生物力学观察:术后4周腱-骨界面拔出率为85%,骨.骨界面为15%;术后8周腱.骨界面拔出率为95%,骨.骨界面为5%;各时间点骨.骨界面拔出率与腱一骨界面拔出率比较差异均有统计学意义(P<0.001). 结论 ACL重建术后早期骨一骨界面较腱.骨界面在愈合强度和速度上具有优势.     

韧带重建术后腱-骨界面愈合相关研究进展

腘绳肌肌腱重建前交叉韧带是目前受欢迎的术式,影响其疗效的最主要环节为术后早期腱-骨界面愈合.不良愈合如瘢痕组织形成、骨隧道扩大可能是术后腱-骨界面连接不牢固的原因之一.如何促使术后腱-骨界面连接并形成近似生理性止点成为众多研究者的共同目标.多数研究发现,移植物周围早期炎症反应所形成的瘢痕组织、缓慢有限的骨长入、缺乏足够数量祖细胞、缺乏协调组织再生的信号分子等可能是腱-骨界面不能有效愈合的原因.调控炎症、促进骨长入、干细胞应用、细胞生长因子应用以及相关物理疗法、组织工程等综合方法等,或可成为促进腱-骨界面愈合的有利措施.     

大鼠关节外骨隧道-游离肌腱移植模型的建立

 目的 建立大鼠关节外骨隧道-游离肌腱移植模型,通过对移植肌腱和骨隧道愈合界面的组织学、生物力学和影像学分析,评价其作为早期腱-骨愈合研究模型的有效性。方法 将成年雄性 Wistar 大鼠左侧后肢的趾浅屈肌腱制成自体游离肌腱（移植物）,植入同侧胫骨近端直径 1.2 mm 骨隧道内建立关节外骨隧道-游离肌腱移植模型。分别于术后 1、2、4、6 周（n=4）处死取材,组织学观察腱-骨界面组织形态学演变过程;于术后第 2、6 周（n=6）进行生物力学测试,测定移植肌腱最大抗拔出应力并记录其衰竭模式,对完成生物力学测试的胫骨标本同时进行高分辨率 X 线成像,观察骨隧道的影像学改变。结果 组织学检查显示腱-骨界面早期由一层不定形的疏松纤维肉芽组织构成,随后腱-骨界面组织厚度逐渐减小,周围的新生骨组织逐渐长入并替代肉芽组织;术后 6 周,腱-骨界面基本消失,移植肌腱与周围骨组织之间可见大量锚固纤维形成。术后 6 周肌腱平均最大抗拔出应力隧道长度比为（1.00±0.30）N/mm,明显高于术后 2 周组（0.35±0.17）N/mm;衰减模式在术后 2 周以肌腱拔出为主,而术后 6 周以肌腱实质性断裂为主。高分辨率 X 线成像显示术后 2 周骨隧道与周围骨间隙清晰,而术后 6 周骨隧道密度与周围骨相当,间隙变得模糊不清,隧道周围可见小梁骨的改建。结论 大鼠关节外骨隧道内游离肌腱的愈合模式在早期与关节内十字韧带重建模型类似,具有手术操作简单、适合双侧肢体同时造模且造模术后对关节活动影响小等优点,是研究早期腱-骨愈合的良好模型。     

骨-髌腱-骨自体移植重建前十字韧带的研究

目的探讨使用骨-髌腱-骨自体移植重建前十字韧带(ACL)术后1年内重建物生物力学性能和组织学变化。方法在39只成年犬单侧后肢行骨-髌腱-骨自体移植重建ACL手术。术后分别在4、8、12、26和52周时处死动物,对正常对照侧ACL和手术侧重建物在屈膝90°行拉力试验直到完全断裂,记录断裂位置,计算横断面积、强度、刚度和应力,观察关节内和隧道内韧带转化过程及隧道内骨块-隧道壁、髌腱-隧道壁和骨块-髌腱三个界面的组织学愈合过程。结果术后隧道内骨块-隧道壁界面4周时愈合;髌腱-隧道壁界面52周时有Sharpey样纤维跨过,出现潮线,软骨细胞有成行排列的趋势;术后骨块-髌腱界面未钙化的纤维软骨层消失,52周时仍未重现;韧带在关节内和隧道内部分的转化过程相似,其结构均于26周时与正常ACL相似。生物力学试验显示所有重建物均在韧带部断裂。52周时,移植髌腱的强度、刚度和应力分别为对照侧的38%、58%和50%,差异有统计学意义。骨隧道内的骨-骨界面术后4周时愈合,早于骨-腱界面;骨-腱界面52周时表现为间接止点,界面出现成行排列趋势的软骨细胞,界面的愈合过程仍在继续。结论用挤压螺钉固定的重建物在手术4周以后,力学薄弱处始终位于韧带本身,在指导患者进行康复锻炼时不必担心固定止点的力学性能。挤压螺钉固定的止点不仅在术后即刻稳定,而且在止点愈合、韧带化过程中仍然保持力学性能可靠。术后1年时虽然韧带在组织学上与正常ACL相似,但力学性能显著低于正常,在剧烈活动时患者需配带支具等进行保护。     

rhBMP-2对兔肩袖损伤重建术后腱-骨愈合的组织学及生物力学研究

[目的]评价重组人骨形态发生蛋白2(rhBMP-2)对兔肩袖损伤重建术后的修复效果。[方法]48只8个月龄雄性新西兰大白兔双侧冈上肌腱行急性损伤后重建其在肱骨大结节上的止点,术后随机分为3组,每组16只,32侧,实验组在腱骨界面注射以纤维蛋白胶为载体的rhBMP-2;实验对照组仅填充纤维蛋白胶;空白对照组术后不给予任何干预。于术后8周取出各组8侧肩袖标本行组织形态学检查,分别于术后2、4、8周分批随机取出各组8侧肩袖标本行生物力学测试。[结果]组织学分析表明,术后8周实验组腱骨界面出现有明显的Sharpey′s纤维连接,出现类似直接止点的四层结构。而实验对照组及空白对照组腱骨界面以结缔组织为主,出现部分Sharpey′s纤维结构及新骨形成。生物力学测试显示,术后各组腱骨界面的抗拉强度及刚度均随着康复时间的延长而不断增强,而且各个时间点实验组腱骨界面的抗拉强度及刚度均显著高于实验对照组及空白对照组,差异有统计学意义(P0.01)。[结论]rh-BMP-2可以在术后明显增强腱骨界面的抗拉强度及刚度,促进腱骨界面形成类似直接止点的特有结构,可很好的修复肩袖损伤。     

酸性成纤维细胞生长因子复合胶原蛋白对兔前交叉韧带重建后腱-骨愈合的影响

目的观察酸性成纤维细胞生长因子(a FGF)复合胶原蛋白对兔前交叉韧带(ACL)重建后腱-骨界面愈合的影响。方法将30只新西兰白兔随机分为实验组与对照组,每组15只,均取趾长伸肌腱作为移植物。实验组将a FGF/胶原蛋白复合物植入到重建的ACL腱-骨界面,对照组单纯行ACL重建。于术后第4、8、12周分别处死动物取材,将股骨与胫骨端分别固定于生物力学试验机上,测试移植肌腱的腱-骨界面抗拉伸强度,取其绝对值作比较;同时,将股骨隧道和胫骨隧道纵向剖开,取下标本组织学观察移植物界面愈合情况。结果术后第4、8、12周抗拉力强度实验组强于对照组,差异有统计学意义(P0.001)。两组动物均在第4周时移植物与骨隧道之间均形成了纤维结缔组织。术后第12周,实验组肌腱移植物在骨隧道内形成了纤维软骨移行带,类似于正常的纤维软骨连接,而对照组则形成了走向与骨隧道轴向垂直的Sharpey样纤维。结论a FGF复合胶原蛋白能促进兔ACL重建腱-骨界面的早期直接愈合。     

成体干细胞技术促肩袖损伤修复实验研究进展

由于肩袖损伤修复术后再撕裂率较高,有学者采用不同种类成体干细胞来修复肩袖损伤以降低再撕裂率。目前多数实验研究证实,成体干细胞具有提高肩袖损伤修复术后腱-骨界面最大失效负荷、增加肩袖胶原蛋白生成、促进界面纤维软骨形成、减少再撕裂率的作用;多种因素在成体干细胞促进损伤肩袖腱-骨界面愈合过程中起了诱导分化的作用。该文就成体干细胞技术促肩袖损伤修复实验研究进展作一综述。     

骨质疏松对肩袖损伤修复的影响研究进展

老年人群因合并有不同程度的骨质疏松,肩袖损伤修复再撕裂率高。为解决这一难题,手术医师尝试通过增加锚钉初始固定强度、改变局部骨质情况等方法来降低这类患者肩袖损伤的再撕裂率。组织工程学的快速发展也使生长因子的辅助应用成为可能。但在目前的临床工作中,合并有骨质疏松的肩袖损伤修复仍然是临床工作者面临的一个巨大挑战。如何更好地增加锚钉固定强度,改善腱骨愈合微环境,降低肩袖再撕裂率成为了近年来的研究热点。本文从骨质疏松与肩袖损伤的关系、骨质疏松对肩袖腱骨愈合的影响及目前采用的减少骨质疏松对腱骨愈合的不同方法3个方面进行综述,以便更好地指导临床治疗,提高患者的手术效果及术后满意率。     

Cell‐based tissue engineering augments tendon‐to‐bone healing in a rat supraspinatus model

Rotator cuff pathology causes substantial pain/disability and health care costs. Cell‐based tissue engineering offers promise for improved outcomes in tendon to bone healing. Cells from the tendon‐bone interface were used here to amplify surgical defect healing in a rat model. Cells from tendon‐to‐bone interface of the rotator cuff were seeded in sponges and implanted into critical rotator cuff defects: Group I, control; II, surgical defect only; III, suture‐repaired defect; IV, surgical defect, repair with sponge only; V, surgical defect, repair with sponge with cells. Three, 6‐, and 12‐week results were assessed for histologic features. At 3 weeks, histologic indices in Group V were significantly increased versus other treatment groups. Group V (12 weeks) showed significantly improved collagen organization versus other treatment groups; there was no difference in collagen organization in Group I versus V. In summary, increased cellularity, inflammation, vascularity, and collagen organization were present at 3 weeks; increased collagen organization at 12 weeks in Group V provides evidence for improved healing with cells. Data further support the utility of tendon‐bone interface cells in rotator cuff healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 407–412, 2013     

Editorial Commentary: Rotator Cuff Repairs Fail at an Alarmingly High Rate During Long-Term Follow-Up: Graft Augmentation and Biologics May Improve Future Outcomes

Rotator cuff repairs (RCR) frequently fail to heal, particularly those with advanced fatty infiltration, supraspinatus and infraspinatus atrophy, narrowed acromiohumeral distance, and large-to-massive tear size. Unfortunately, the longer the follow up, the more sobering the statistics, with some reported retear rates ranging up to 94%. Importantly, recent long-term radiographic assessments after primary RCR reveal direct correlations between failure and patient-reported outcomes, functional deterioration, and ultimately, progression of glenohumeral arthritis and/or frank cuff tear arthropathy. As shoulder surgeons, we must continue to seek out novel approaches to improve tendon to bone healing and recapitulate the native rotator cuff enthesis. In doing so, we hope to engender more sustained subjective and objective results for our patients over time. Investigations are ongoing into several biomechanical and biological or structural adjuncts, from platelet-rich plasma and bone marrow aspirate concentrate to autograft or allograft structural augments. We must continue to push the envelope and refuse to settle for the current reality and alarmingly high failure rates following RCR.     

Editorial Commentary: Platelet-Rich Plasma in the Treatment of Rotator Cuff Tears—From Hero to Zero?

As failure rates after arthroscopic rotator cuff remain high, platelet-rich plasma (PRP) has gained interest as a potential biological augmentation to enhance bone–tendon healing. Recent research shows that delayed PRP application fails to significantly improve clinical results or decrease retear rates but may result in less fatty-infiltration of the repaired rotator cuff muscles. In combination with a lower trend toward retear, this may hint that we should not bid farewell to PRP in rotator cuff repair just yet, and whether our current enthusiasm for emerging biological strategies in rotator cuff repair is justified remains subject to additional investigation.     

Arthroscopic Rotator Cuff Repair: How to Avoid Retear

A healed rotator cuff repair results in a superior outcome for the patient compared with a non-healed repair. The surgeon can maximize the chance of a healed repair by knowing the end-point of each key step in the repair process and adhering to a few core principles. First, the rotator cuff tear pattern (e.g. crescent, L-tear, reverse L-tear, U-tear) must be recognized, starting with careful assessment of preoperative MRI but concluding with the arthroscopic assessment of tear edge mobility. Second, a low-tension, anatomic, and mechanically robust repair construct (e.g. linked, double row; load-sharing rip stop; margin convergence to bone) must be determined based on the tear pattern. Increasingly, surgeons are recognizing the importance of the superior capsule of the shoulder, which can appear as a separate pathoanatomic structure in a delaminated rotator cuff tear and require independent suturing in the repair construct. Third, the biological healing capacity of the repair site must be optimized by using meticulous preparation of the greater tuberosity bone, including removal of soft tissue remnants, light burring, and creation of bone vents. Finally, avoid aggressive early rehabilitation after arthroscopic rotator cuff repair respecting that tendon to bone healing is unlikely to occur before 12 weeks postoperatively. Sling immobilization and judicious use of early passive motion should be used for the first 6 weeks, with passive shoulder range of motion performed during weeks 6-12 postoperatively. Rotator cuff strengthening, and active overhead use of the arm should be delayed until at least 12 weeks after surgery to minimize the risk of retear.     

Die Biologie der Heilung der Rotatorenmanschettenl?sion

Rotator cuff tears are a common orthopedic diagnosis in daily practice. The failure rate is still high despite the continued developments in suture material and techniques in both the open and arthroscopic approaches. In recent years, the physiological processes in the bone tendon insertion as well as the biological characteristics of rotator cuff healing have received increasing attention by researchers. It has been shown that the healing of the tendon bone insertion is a complex interplay of local cells, progenitor stem cells, extracellular matrix, growth factors, and other cytokines. Accordingly, several biological in vitro and in vivo therapy methods were developed to improve reinsertion. This article provides an overview of the current evidence for augmentation of rotator cuff reconstruction with growth factors. Furthermore, potential future therapeutic approaches are discussed.     

Graft Augmentation of Repairable Rotator Cuff Tears: An Algorithmic Approach Based on Healing Rates

We provide our algorithm for tissue augmentation of rotator cuff repairs based on the current available evidence regarding rotator cuff healing. A variety of factors are associated with healing following rotator cuff repair. Increasing tear size and retraction as well as severe fatty degeneration have been associated with worsening rates of tendon healing. Given the correlation between tendon healing and postoperative outcomes, it is important to identify patients at high risk for failure and to modify their treatment accordingly to minimize the risk of early biomechanical failure and maximize the potential for structural healing. One approach that may be used to improve healing is tissue augmentation. Tissue augmentation is the use of tissue patches and scaffolds to provide rotator cuff reinforcement. Surgical management for rotator cuff tears (RCTs) continues to be a challenging task in orthopaedic surgery today. Appropriate treatment measures require an in depth understanding and consideration of the patient’s prognostic factors such as age, fatty infiltration of the rotator cuff muscles, bone mineral density, rotator cuff retraction, anteroposterior tear size, work activity, and degenerative changes of the joint. Using these factors within the Rotator Cuff Healing Index, we can determine a patient’s surgical treatment that will yield the maximum healing rate. For nonarthritic RCTs, joint-preserving strategies should be first-line treatment options. For young, active patients with a reparable RCT and minimal fatty infiltration, a complete repair can be effective. For young patients with irreparable RCTs, superior capsular reconstructions, and tendon transfers are viable options. For elderly patients with low work activity, an irreparable RCT and significant fatty infiltration, a partial repair with or without graft augmentation can be attempted if minimal to no arthritic changes are seen.Level of EvidenceLevel V, expert opinion.     

Preoperative Shoulder Corticosteroid Injection Is Associated With Revision After Primary Rotator Cuff Repair

Rotator cuff surgery should be delayed in patients receiving frequent or recent shoulder steroid injections. That said, success rates after rotator cuff surgery are high, and injection is but one of a number of factors associated with retear after rotator cuff repair.     

Biologic augmentation of rotator cuff repair

Rotator cuff repair is commonly performed to provide pain relief and improve shoulder function in patients with pain and disability related to cuff tears. However, re-tear rates following repair remain remarkably high in certain patient populations. Biologic strategies to reinforce repairs or augment tendon healing, such as extracellular matrices and platelet-rich plasma therapy, are an area of increased interest among orthopedic surgeons to improve these suboptimal healing rates. As more products have become commercially available, much attention has been turned to determining the optimal augmentation technique. However, data supporting the role and efficacy of these products is limited. Thus careful patient selection remains the most essential strategy for optimizing tendon healing potential following rotator cuff repair.