屏障材料预防肌腱粘连的研究进展

肌腱与腱周组织粘连是肌腱损伤修复术后最主要的并发症,使用屏障材料预防肌腱粘连是一种最直接有效的方法。传统使用的不可吸收材料常常会导致严重免疫反应或阻隔肌腱营养而导致肌腱愈合不良,且常需二次手术取出,已基本淘汰。可吸收膜和水凝胶等具有良好通透性及组织相容性的可吸收大分子材料是目前研究的重点。使用自体或异体组织材料重建腱鞘也可预防肌腱粘连,但自体组织重建腱鞘损伤较大且手术复杂,异体组织常常受到安全性、伦理学等诸多限制,而组织工程化腱鞘可能是未来预防肌腱粘连的一个重要研究方向。     

屏障材料预防肌腱粘连的研究进展

肌腱与腱周组织粘连是肌腱损伤修复术后最主要的并发症,使用屏障材料预防肌腱粘连是一种最直接有效的方法。传统使用的不可吸收材料常常会导致严重免疫反应或阻隔肌腱营养而导致肌腱愈合不良,且常需二次手术取出,已基本淘汰。可吸收膜和水凝胶等具有良好通透性及组织相容性的可吸收大分子材料是目前研究的重点。使用自体或异体组织材料重建腱鞘也可预防肌腱粘连,但自体组织重建腱鞘损伤较大且手术复杂,异体组织常常受到安全性、伦理学等诸多限制,而组织工程化腱鞘可能是未来预防肌腱粘连的一个重要研究方向。     

前臂屈指肌腱修复术后功能恢复的影响因素分析

目的：探讨影响前臂屈指肌腱修复术后功能恢复效果的因素,以利于制定合理的手术及康复方案。方法：对2011年1月～2012年10月解放军第401医院手外科收治的58例（其中男性41例,女性17例,年龄13．62岁,平均33．8岁）屈指肌腱在前臂损伤患者的伤因及手术方式进行回顾、分析总结并进行随访,分析其受伤严重程度、手术方式、术后功能锻炼情况。结果：术后随访54例,失访4例,随访时间为术后3-6个月。根据中华医学会手外科学会手功能评定试用标准评定54例前臂屈指肌腱损伤修复术后的患手的恢复情况,其中优31例,良16例,中5例,差2例。指浅、深屈肌腱同时损伤较单纯指浅屈肌腱损伤修复术后粘连发生率较高,手功能的优良率较低（P〈0．05）,合理应用防粘连技术和术后进行系统功能锻炼的患者术后手功能的优良率分别较未合理应用防粘连技术和术后未进行系统功能锻炼的患者显著升高（P〈0．05）。结论：手术切口是否合理的延长,术中操作是否重视无创操作,是否合理的应用防粘连技术以及缺乏系统的功能锻炼以及肌腱断端吻合质量是影响前臂屈指肌腱修复术后功能恢复的重要因素。     

前臂屈指肌腱修复术后功能恢复的影响因素分析

目的:探讨影响前臂屈指肌腱修复术后功能恢复效果的因素,以利于制定合理的手术及康复方案。方法:对2011年1月~2012年10月解放军第401医院手外科收治的58例(其中男性41例,女性17例,年龄13-62岁,平均33.8岁)屈指肌腱在前臂损伤患者的伤因及手术方式进行回顾、分析总结并进行随访,分析其受伤严重程度、手术方式、术后功能锻炼情况。结果:术后随访54例,失访4例,随访时间为术后3~6个月。根据中华医学会手外科学会手功能评定试用标准评定54例前臂屈指肌腱损伤修复术后的患手的恢复情况,其中优31例,良16例,中5例,差2例。指浅、深屈肌腱同时损伤较单纯指浅屈肌腱损伤修复术后粘连发生率较高,手功能的优良率较低(P0.05),合理应用防粘连技术和术后进行系统功能锻炼的患者术后手功能的优良率分别较未合理应用防粘连技术和术后未进行系统功能锻炼的患者显著升高(P0.05)。结论:手术切口是否合理的延长,术中操作是否重视无创操作,是否合理的应用防粘连技术以及缺乏系统的功能锻炼以及肌腱断端吻合质量是影响前臂屈指肌腱修复术后功能恢复的重要因素。     

低强度脉冲超声波对肌腱愈合的促进作用

目的:分析低强度脉冲超声波(low intensity pulsed ultrasound,LIPU)对Ⅱ区屈指肌腱愈合的促进作用,并探讨其减少肌腱粘连的临床效果。方法:选取2010年8月至2013年4月在我院接受II区屈指肌腱损伤修复术治疗的患者80例并随机分为两组。LIPU组(33例,共39指),该组患者均接受系统的低强度脉冲超声波进行治疗;对照组(34例,共41指),所有患者在治疗时放置超声探头,但不接通电源。在术后12周,采用视觉模拟评分法(visual analogue scale,VAS)评估患手疼痛程度;采用肌腱总主动活动度(total active motion,TAM)评定标准评价肌腱的功能状况;采用Lovett分级法评价患指屈指肌力。结果:两组术后无肌腱再断裂病例出现。术后12周时,LIPU组与对照组的VAS疼痛评分分别为(1.9±1.8)和(2.3±1.9)(t=0.996,P=0.337)。根据TAM系统评定标准,LIPU组与对照组的优良率分别为94.9%和70.7%,组间差异有统计学意义(X2=12.798,P=0.000),LIPU组显著高于对照组,两组患指屈指肌力恢复正常的发生率分别为100%和95.1%,组间差异无统计学意义(X2=1.951,P=0.162)。结论:LIPU具有促进II区屈指肌腱愈合,改善患指主动活动功能的效果,且不增加肌腱断裂的风险,但其促进肌腱愈合的机制尚需进一步实验研究证实。     

丹参注射液对同种异体肌腱移植后粘连防治的实验研究

目的:探讨局部应用丹参注射液(Salvia Miltiorrhiza,SM)对异体肌腱移植后粘连的影响.方法:使用深低温冷冻处理的同种异体肌腱修复缺损的大鼠屈趾肌腱,72只大鼠随机分为2组,A组为试验组,腱周局部注射丹参注射液,B组为对照组,注射生理盐水(Saline).术后2、4、8周处死动物,标本进行大体观察、组织学观察及生物力学测定.结果:A组粘连范围小,粘连等级评分与B组相比有统计学意义,力学测定结果显示A组与B组无统计学意义.结论:丹参注射液能有效减轻肌腱移植后粘连.     

丝裂霉素C预防肌腱粘连的实验研究

目的:探讨丝裂霉素C(mitomycin C,MMC)对肌腱粘连的影响.方法:SD大鼠80只,右足为丝裂霉素C组,左足为生理盐水组.以屈趾肌腱为试验对象,切断后采用改良Kessler法缝合.右足吻合处用0.4mg/ml MMC脑棉片湿敷5分钟,生理盐水反复冲洗3次;左足生理盐水脑棉片湿敷5分钟,生理盐水反复冲洗3次.术后1、2、4、8周处死动物,收集2组屈趾肌腱分别进行大体观察、组织学观察和羟脯氨酸含量测定.结果:丝裂霉素C组肌腱粘连程度较生理盐水组明显减轻,有统计学意义(P＜0.05),羟脯氨酸含量在术后2、4、8周较生理盐水组增高.结论:丝裂霉素C有防止肌腱粘连的作用.     

肌腱组织工程支架与种子细胞研究进展

目的:综述肌腱组织工程支架材料、细胞来源、制备技术及体外构建的研究进展.方法:查阅近期肌腱组织工程研究的相关文献,对组织工程肌腱支架的材料来源、制备技术,复合细胞种类,体外构建力学刺激等进行分析、归纳.结果:肌腱组织工程支架材料有天然材料、人工合成材料及复合材料等;制备技术包括静电纺丝和编织法等;其中支架材料的表面修饰是组织工程化肌腱构建的重要环节.与肌腱材料进行复合的种子细胞有肌腱细胞、骨髓间充质干细胞及成纤维细胞等.结论:复合材料是近年肌腱组织工程支架材料研究的重点,静电纺丝技术是一种具有潜力的支架制备技术,支架材料的表面修饰可促进细胞在支架上的黏附及肌腱的形成,种子细胞的研究仍是肌腱组织工程发展的瓶颈,周期性张力的存在为组织工程化肌腱的形成创造了条件.     

丝素蛋白布洛芬复合凝胶预防肌腱粘连的作用研究

目的:探讨丝素蛋白布洛芬复合凝胶对肌腱粘连的预防作用及愈合后肌腱功能的影响。方法:选取体重2.5 Kg-3.5 Kg成年雄性来亨(Leghorn)鸡90只,随机分成3组,每组30只。将左足第三趾趾深屈肌腱横断后,采用改良Kessler缝合法缝合肌腱,A组动物直接缝合,B组动物在肌腱横断处周围注入丝素蛋白凝胶,然后逐层缝合,C组动物在肌腱横断处周围注入丝素蛋白布洛芬复合凝胶。在术后1、3、6周处死并取材分别进行大体实验观察、组织学观察和生物力学测定,在术后6周进行关节活动度评定。结果:术后1、3、6周,创口无感染流脓,创口愈合较好,C组肌腱粘连程度评分和肌腱功能评价显著优于B组和A组。C组细胞炎性反应较少,与周围组织粘连程度较轻,纤维组织排列较规则;B组有细胞炎性浸润反应,且与周围组织程中度粘连,纤维组织排列不规则;A组细胞炎性反应明显,与周围组织粘连较重,分界不清,纤维组织排列杂乱无序。术后3、6周,各时间点肌腱滑动距离C组最远,B组好于A组,两两比较,C组与A、B两组之间有明显差异(P0.05)。术后3周、6周C组肌腱主动屈曲功优于B组,A组最差,两两比较,肌腱主动屈曲功比值存在差异具有统计学意义(P0.05)。肌腱术后功能测定比较,C组趾关节活动度明显优于B组,A组最差,术后各组肌腱趾关节活动度组间差异具有统计学意义(P0.05)。结论:丝素蛋白布洛芬复合凝胶可以有效防止肌腱粘连,且不影响术后肌腱的功能。     

影响腱-骨愈合因素的研究新进展

随着运动爱好者逐渐增多,运动带来的膝关节损伤也与日俱增。前交叉韧带断裂是常见的膝关节运动损伤,目前手术是其主要治疗方法,术中取自体肌腱编制成韧带重建前交叉韧带(Anterior Cruciate Ligament,ACL)。因此,肌腱与骨的愈合直接影响着手术效果。那么,如何加速肌腱与骨的愈合是关节外科医生最关心的问题。近年来研究发现,多种因素可通过改变腱骨结合面的局部微环境对腱-骨愈合起到抑制或促进作用。其中,增强相关生长因子活性、加入自体骨膜、运用中药治疗等措施可加快腱-骨愈合;关节液等不利因素可减慢腱-骨愈合。因此,合理增加有利因素,减少不利因素可缩短愈合周期,加速术后康复,进而提高手术效果。本文就目前影响腱骨愈合因素的最新进展作一综述。     

组织工程化肌腱研究进展

肌腱损伤常发生在日常的工作和运动中,世界范围内每年有超过3000万人肌腱损伤。目前,尽管临床上对于肌腱损伤可以采取非手术、手术和康复等多种手段进行治疗,但这些传统治疗手段的效果均差强人意。修复后的肌腱很难恢复到损伤前的功能状态。肌腱损伤的治疗也成了运动医学研究的重点。随着组织工程技术的发展,组织工程化肌腱为解决这一难题提供思路。其与传统的肌腱损伤的治疗手段相比,不再有自体供区功能缺失,及异体移植肌腱的排异等问题。     

Tendon stem/progenitor cell ageing: Modulation and rejuvenation

Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.     

Known data on applied regenerative medicine in tendon healing

Tendons and ligaments are important structures in the musculoskeletal system. Ligaments connect various bones and provide stability in complex movements of joints in the knee. Tendon is made of dense connective tissue and transmits the force of contraction from muscle to bone. They are injured due to direct trauma in sports or roadside accidents. Tendon healing after repair is often poor due to the formation of fibro vascular scar tissues with low mechanical property. Regenerative techniques such as PRP (platelet-rich plasma), stem cells, scaffolds, gene therapy, cell sheets, and scaffolds help augment repair and regenerate tissue in this context. Therefore, it is of interest to document known data (repair process, tissue regeneration, mechanical strength, and clinical outcome) on applied regenerative medicine in tendon healing.     

Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair

Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1) expression in the antagonist group, along with decreases in type I collagen (Col1a1). Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism would improve the healing phenotype, these results highlight the complex role of EP4 signaling during tendon repair.     

Exosomes from tendon stem cells promote injury tendon healing through balancing synthesis and degradation of the tendon extracellular matrix

Tendon injuries are common musculoskeletal system disorders in clinical, but the regeneration ability of tendon is limited. Tendon stem cells (TSCs) have shown promising effect on tissue engineering and been used for the treatment of tendon injury. Exosomes that serve as genetic information carriers have been implicated in many diseases and physiological processes, but effect of exosomes from TSCs on tendon injury repair is unclear. The aim of this study is to make clear that the effect of exosomes from TSCs on tendon injury healing. Exosomes were harvested from conditioned culture media of TSCs by a sequential centrifugation process. Rat Achilles tendon tendinopathy model was established by collagenase‐I injection. This was followed by intra‐Achilles‐tendon injection with TSCs or exosomes. Tendon healing and matrix degradation were evaluated by histology analysis and biomechanical test at the post‐injury 5 weeks. In vitro, TSCs treated with interleukin 1 beta were added by conditioned medium including exosomes or not, or by exosomes or not. Tendon matrix related markers and tenogenesis related markers were measured by immunostaining and western blot. We found that TSCs injection and exosomes injection significantly decreased matrix metalloproteinases (MMP)‐3 expression, increased expression of tissue inhibitor of metalloproteinase‐3 (TIMP‐3) and Col‐1a1, and increased biomechanical properties of the ultimate stress and maximum loading. In vitro, conditioned medium with exosomes and exosomes also significantly decreased MMP‐3, and increased expression of tenomodulin, Col‐1a1 and TIMP‐3. Exosomes from TSCs could be an ideal therapeutic strategy in tendon injury healing for its balancing tendon extracellular matrix and promoting the tenogenesis of TSCs.