细胞工程技术在肩袖损伤修复中的应用

 肩袖损伤是最常见的需要外科干预的损伤之一。自从Codman于1911第一次介绍了肩袖修补术后,肩袖损伤的治疗方式已经从开放手术逐渐过渡到小切口手术,再到全关节镜手术。虽然手术技巧日趋成熟及完善,但术后再撕裂的发生率仍然很高。文献报道中单纯冈上肌损伤术后的再撕裂率约为25%,巨大肩袖损伤的再撕裂率甚至高达75%。再撕裂率与患者年龄、肌腱的变性情况、肌腱质量、手术操作及术后康复有关。因为肩袖组织血供相对缺乏,损伤后发生一系列退行性变化,如脂肪变性、肌肉萎缩等,手术修复后腱-骨连接处主要以瘢痕组织为主,机械强度远比正常的纤维软骨性腱-骨愈合的结构差,肩袖修补后的机械强度无法恢复到自然状态。因此探讨肩袖的自身修复机制,在此基础上通过调节其生物过程来促进肩袖损伤修复,达到肩袖止点的生物学重建较单纯提高手术技术更为重要。近年来,有学者认为组织自身的微环境所诱导出的愈合能力是肩袖修补转归的重要因素之一。研究方向更多地转向了肌腱修复的生物原理,使肌腱可以有二次生长的机会,最终达到治疗目的。     

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。     

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。     

肩袖撕裂修补术后腱骨愈合的研究进展

肩袖撕裂是导致肩关节疼痛和活动受限的常见疾病,随着手术技术的进步,关节镜下修补成为主流方式。尽管如此,术后依旧有很高的再撕裂率,而腱骨界面的愈合不佳主要原因是腱骨界面未能形成正常组织结构反而形成瘢痕化,因腱骨界面的组织学改变导致其生物力学性能下降,易再次发生撕裂。近年来,越来越多的学者致力于生物学、生物力学的研究,希望能够加速腱骨愈合的进程,恢复腱骨界面的正常组织结构,本文就影响腱骨愈合常见4个因素(炎症反应、缓慢而有限的骨长入、不当的机械刺激、不足的干细胞)及物理治疗的研究进展进行综述。     

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。     

全关节镜与关节镜辅助下小切口肩袖修补术临床疗效的比较

目的探讨全关节镜下肩袖修补术与关节镜辅助下小切口肩袖修补术临床疗效的比较。方法回顾性研究了复旦大学附属华山医院在2004年3月至2006年12月间,对56肩(55例患者)肩袖撕裂患者进行两种修补方法的疗效比较,至少随访19个月,平均随访27个月。分为A组30肩(29例患者),B组26肩(26例患者);A组患者采用关节镜辅助下小切口肩袖修补术;B组患者采用全关节镜下肩袖修补术。患者随访资料包括,住院时间、并发症、关节活动度、肌力、MRI评价术后肩袖愈合情况等,并进行UCLA、VAS及ASES评分,两组进行比较。结果两组患者手术后ASES、UCLA、VAS评分测试结果均较术前有明显改善,差异具有统计学意义(P0.01);但两组组间术后评分改善情况的比较无统计学意义(P0.05)。MRI发现A组再撕裂4例(13.3%),B组再撕裂3例(11.5%),两组间的差别无统计学意义(P0.05);再撕裂患者与肩袖完整患者相比,术后ASES、UCLA、VAS评分的改善情况无统计学意义(P0.05)。结论全关节镜下肩袖修补与小切口肩袖修补治疗肩袖撕裂的临床疗效在2～3年的随访期内并无统计学差异,再撕裂的发生率为10%～15%,肩袖再撕裂与肩袖完整患者在功能方面无统计学差异。     

富血小板血浆治疗肩袖损伤的研究进展

肩袖损伤是肩关节常见损伤之一。其腱骨结合部位为骨、纤维软骨、肌腱多层结构移行的特殊组织,同时又是肩关节的应力集中点,因此一旦发生损伤常难以自愈。虽然可以通过手术治疗的方式对肩袖组织进行修补,但术后较高的再撕裂率仍是影响预后的一个重要因素。富血小板血浆（platelet-rich plasma,PRP）由自体全血浓缩得到...     

关节镜下肩袖肱骨止点内移技术与传统技术治疗巨大肩袖撕裂的疗效比较

目的 :探讨关节镜下肩袖肱骨止点内移技术的可行性,为治疗巨大肩袖撕裂提供一种方案。方法 :自2014年2月至2018年4月行手术治疗巨大肩袖撕裂患者40例,分成2组,研究组20例,男8例,女12例,年龄42～82(57.55±8.90)岁,病程1 h～2年;采用肩袖在肱骨头处止点内移,重建完整肩袖技术治疗巨大肩袖撕裂;对照组20例,男10例,女10例,年龄45～75(57.75±9.10)岁,病程1 h～5年,采用传统清理后部分缝合肩袖或原位高张力下缝合技术治疗巨大肩袖撕裂。采用VAS评分、Constant评分、UCLA评分评价两组临床疗效。结果:40例患者均获随访,时间12～14个月。两组术后VAS评分、Constant评分、UCLA评分与术前比较均明显改善(P0.05);研究组在VAS评分、Constant评分和UCLA评分及疗效明显优于对照组(P0.05)。结论:关节镜下肩袖肱骨止点内移治疗巨大肩袖撕裂在肩关节疼痛缓解,功能改善满意,治疗巨大肩袖撕裂是一种可行的方案。     

肌腱干细胞的研究进展

由运动损伤导致的跟腱断裂、肩袖撕裂、肌腱止点撕脱等常需通过手术修复,然而肌腱组织再生能力较差,患者术后将面临肌腱的瘢痕愈合或骨-腱接点愈合困难的问题.最近新发现的肌腱干细胞已被证实具有干细胞的特性,其在肌腱组织中的修复潜能逐渐获得人们的重视,有望成为组织工程中新的种子细胞.本文对肌腱干细胞的一般特性与年龄、微环境、力学的关系及其在骨-腱接点愈合中的作用作一综述.     

自体腘绳肌腱修复兔巨大肩袖缺损的实验研究

目的研究自体腘绳肌腱修复兔巨大肩袖缺损腱骨愈合的早期实验效果。方法将40只成年雄性新西兰大白兔随机分为3组,分别为正常组(n=8)、模型组(n=8)和实验组(n=24)。正常组相同方式饲养但不予手术处理;模型组将大白兔双前肢肱骨头大结节处切取1.5 cm×1.0 cm的肩袖组织缺损,不予缝合修补后直接缝合皮肤;实验组在模型组的基础上用自体腘绳肌腱修复巨大肩袖缺损。实验组分别于术后第8、16、24周时安乐死8只大白兔后取出双肩标本。将标本处理后分别进行组织形态学分析和生物力学研究测试。结果组织形态学分析结果显示:实验组术后24周腱骨界面胶原纤维明显增多,腱骨隧道连接处可见Sharpey纤维、纤维软骨细胞及纤维软骨等腱骨愈合成分。生物力学研究结果显示实验组肌腱最大负荷随时间延长呈持续增大趋势(各时间点之间比较,P<0.05),术后24周可以获得较强的力学强度。结论应用自体腘绳肌腱修复兔巨大肩袖缺损可以获得良好的腱骨愈合。     

Editorial Commentary: Monitoring Tendon and Muscle Recovery After Rotator Cuff Repair Using Diagnostic Ultrasound Demonstrates that Early Repair is Beneficial for Many Patients With Reparable Tears

Rotator cuff repair is performed to effect healing of the enthesis; to restore shoulder comfort, strength, and function; to prevent tear propagation; and to prevent progression of atrophic muscle changes (fatty degeneration, fatty infiltration, and fatty atrophy) that eventually occur. Non-retracted and moderately retracted rotator cuff tears usually heal after repair, and muscle atrophy may recover over time. It follows that early rotator cuff repair is beneficial for many patients with chronic but reparable rotator cuff tears. Diagnostic ultrasound can provide quantitative information about the recovery of both muscle and tendon and represents a viable alternative to magnetic resonance imaging for evaluating healing after rotator cuff repair.     

Rotatorenmanschettenheilung

Background

Rotator cuff tears are associated with significant shoulder dysfunction and pain. Despite conservative management, many patients persistently have decreased quality of life warranting surgical repair as a more appropriate treatment option. Using new arthroscopic methods, a wider range of rotator cuff tears can be reconstructed using minimally invasive techniques.

Methods

Biomechanical studies which focus on the repair or reconstruction of the rotator cuff in order to restore function have been published. However, the re-tear rate remains high. This is partially due to the complexity of tendon regeneration, which is largely described as a three-stage process consisting of inflammation, followed by reparation, and finally a remodeling phase. Despite investigation of the biological principles in tendon healing, the mechanism is not yet completely understood. The ability to recreate a native enthesis between tendon and bone after rotator cuff repair is the ideal treatment goal. In addition to surgical treatment, postoperative rehabilitation is also critical to achieve full shoulder function. The appropriate time to start rehabilitation and passive motion is still controversial. To begin immediately may lead to an improvement in range of motion as well as enhanced collagen synthesis by stimulating fibroblasts, while, initiating rehabilitation too soon could risk re-tear or result in inferior healing of the tendon.

Conclusion

Biological augmentation may be an option to improve the healing process, therefore, allowing more rapid rehabilitation without compromising the repair. This article provides an overview of tendon healing principles as well as presumed enthesis stability during the healing process.

     

Tissue‐engineered tendon constructs for rotator cuff repair in sheep

Current rotator cuff repair commonly involves the use of single or double row suture techniques, and despite successful outcomes, failure rates continue to range from 20 to 95%. Failure to regenerate native biomechanical properties at the enthesis is thought to contribute to failure rates. Thus, the need for technologies that improve structural healing of the enthesis after rotator cuff repair is imperative. To address this issue, our lab has previously demonstrated enthesis regeneration using a tissue‐engineered graft approach in a sheep anterior cruciate ligament (ACL) repair model. We hypothesized that our tissue‐engineered graft designed for ACL repair also will be effective in rotator cuff repair. The goal of this study was to test the efficacy of our Engineered Tissue Graft for Rotator Cuff (ETG‐RC) in a rotator cuff tear model in sheep and compare this novel graft technology to the commonly used double row suture repair technique. Following a 6‐month recovery, the grafted and contralateral shoulders were removed, imaged using X‐ray, and tested biomechanically. Additionally, the infraspinatus muscle, myotendinous junction, enthesis, and humeral head were preserved for histological analysis of muscle, tendon, and enthesis structure. Our results showed that our ETC‐RCs reached 31% of the native tendon tangent modulus, which was a modest, non‐significant, 11% increase over that of the suture‐only repairs. However, the histological analysis showed the regeneration of a native‐like enthesis in the ETG‐RC‐repaired animals. This advanced structural healing may improve over longer times and may diminish recurrence rates of rotator cuff tears and lead to better clinical outcomes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:289–299, 2018.     

The tension required at repair to reappose the supraspinatus tendon to bone rapidly increases after injury

Rotator cuff tears occur frequently and can cause significant pain and reduced shoulder function. A high percentage of patients are satisfied after surgical repair of rotator cuff tears, but a smaller percentage of patients with chronic tears continue to have pain and poor shoulder function. This may be partly attributable to an increase in the repair tension, the force required at repair to reappose the tendon to its original insertion site on the humerus. Increases in repair tension have been shown to occur for long-standing ruptures of the supraspinatus tendon, but the precise tension at various times after injury are unknown. Therefore, the objective of the current study was to determine the repair tension at various times after a rotator cuff tear. This was achieved by creating a full-thickness supraspinatus tendon tear in a rat model and measuring the mechanical characteristics of the musculotendinous unit at 0, 2, 4, 9, and 16 weeks after injury. The repair tension rapidly increased initially after injury followed by a progressive, but less dramatic, increase with additional time. These findings suggest that rotator cuff tears should be repaired early in the clinical setting. Future studies will investigate the effect of repair tension on tendon to bone healing after repair.     

Delay of supraspinatus repair by up to 12 weeks does not impair enthesis formation: a quantitative histologic study in rabbits.

The purpose of this study was to find out whether supraspinatus repair delayed by up to12 weeks affects the formation of a new enthesis when compared to an immediate repair. In 67 rabbits, the supraspinatus fibrocartilaginous enthesis of one shoulder was resected. The tendon was attached to the greater tuberosity either immediately, after a 6-week, or after a 12-week delay. Five histologic variables were used to assess enthesis formation: number of non-chondrocytes, number of chondrocytes, alignment of chondrocytes in rows, area of metachromasia on toluidine blue (TB)-stained sections indicating proteoglycan content, and area of diffracted polarized light indicating spatial alignment of collagen fibers. For every variable, progressive enthesis formation was observed. Again, for every variable and at every time point studied, no statistically significant difference was observed between tendons repaired immediately, after 6, or after 12 weeks (all p>0.05). Supraspinatus tendon repairs delayed by 6 and 12 weeks constituted an enthesis which proceeded identically to one immediately repaired. Formation of a fibrocartilaginous enthesis depended on the elapsed time after repair and not on the duration between detachment and repair. Despite stated limitations, these results support both a trial of conservative treatment after a rotator cuff tear and a positive outcome of rotator cuff repair even if delayed by up to 12 weeks.     

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.     

关于骨髓刺激技术在肩袖撕裂治疗作用的系统评价及Meta分析

目的评估骨髓刺激技术在改善肩袖愈合及功能恢复中的作用。 方法计算机检索Cochrane Library、PubMed、Medline、Embase、中国知网（CNKI）、维普（VIP）、万方及中国生物医学文献数据库（CBM）等数据库中关于应用骨髓刺激技术和单纯肩袖修复的比较研究，包括临床随机对照和回顾性队列研究。手工检索纳入研究的参考文献。提取各研究中指标数据，包括总体再撕裂率，大到巨大肩袖撕裂的再撕裂率，术后肩关节活动度（range of motion，ROM），视觉模拟评分（visual analogue scale,VAS），Constant-Murley肩关节功能评分（Constant-Murley score，CMS）,加州福尼亚大学洛杉矶分校评分（University of California, Los Angeles shoulder rating scale，UCLA）,美国肩肘外科协会评分（American shoulder and elbow surgeons score，ASES）,手臂、肩膀和手的残疾问卷（disabilities of the arm, shoulder, and hand questionnaire ，DASH）各项功能评分。运用Revman 5.3软件对其进行分析和处理。 结果共纳入2篇随机对照研究、6篇回顾性队列研究、2篇非对照回顾性研究共10篇文献进行系统回顾，Meta分析只纳入前8篇文献，患者共641例。Meta分析结果显示，与单纯肩袖修复相比，结合骨髓刺激技术能明显改善肩袖总体愈合效果[OR = 0.42，95% CI（0.28，0.63），P< 0.0001]，大到巨大撕裂的肩袖修复术后再撕裂率也明显减少[OR = 0.28, 95% CI（0.13, 0.58）, P = 0.0007]。而在肩关节疼痛VAS评分[SMD = -0.63, 95% CI（-1.40, 0.14）, P = 0.11], ROM外旋[SMD = 0.05, 95% CI（-0.22, 0.32）, P = 0.70]、前屈[SMD = 0.10, 95% CI（-0.17, 0.37）, P = 0.47]，CMS评分[SMD = 0.12, 95% CI（-0.09, 0.32）, P = 0.26]，UCLA评分[SMD = -0.04, 95% CI（-0.29, 0.21）, P = 0.76]，ASES评分[SMD= -0.06，95% CI（-0.33, 0.21）, P = 0.67]及DASH评分[SMD = -0.15, 95% CI（-0.43, 0.13）, P = 0.29]等方面的差异均无统计学意义。 结论与单纯肩袖修复相比，结合骨髓刺激技术能明显改善肩袖修复能力，尤其值得关注的是该技术能够促进大到巨大撕裂肩袖的愈合，而在术后肩关节疼痛、ROM及功能方面未见明显差异。     

反式全肩关节假体置换治疗巨大不可修复肩袖撕裂

目的探讨反式全肩关节置换术（reverse total shoulder arthroplasty,RTSA）治疗巨大不可修复肩袖撕裂的临床治疗效果。 方法对南京中医药大学附属医院2018年5月至2020年1月收治的采取RTSA治疗的13例巨大不可修复肩袖撕裂患者的临床资料进行回顾性分析。记录术前及最后一次随访时患者的肩关节前屈、外展、外旋活动,美国肩肘外科协会评分（American shoulder and elbow surgeons score,ASES）及美国加州大学洛杉矶分校（University of California at Los Angeles,UCLA）评分评估患者肩关节功能。并记录患者发生并发症的情况及影像学检查结果。术前行MR确定肩袖脂肪浸润程度,CT评价肩胛盂骨质情况及有无缺损,术后使用X线评估假体情况。 结果13例患者均随访至少12个月以上。统计术前与术后12个月数据之间的关系,术后12个月肩关节前屈、外展、外旋活动,ASES评分和UCLA评分较术前明显提高,差异具有统计学意义（P<0.01）。随访期内13例患者中有1例患者因局部血肿在术后1周行切开血肿清除引流术,所有患者功能恢复良好。 结论RTSA治疗巨大不可修复肩袖撕裂临床效果良好。     

肩袖撕裂的组织学及电子显微镜观察

目的观察肩袖的损伤过程及超微结构。方法３６例肩袖撕裂的标本分别制成组织切片和电镜超薄切片,比较手术所见与肩袖的病理变化。结果肩袖退变分别由滑膜和肌腱本身发生。肌腱的修复分为两种类型：Ⅰ型通过滑膜组织修复;Ⅱ型通过肌腱本身修复。结论肌腱虽然有自身修复能力,但肌腱全层和深层的断裂难以完全修复,应手术治疗     

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.