TENDON REATTACHMENT USING DEMINERALISED BONE MATRIX AND MESENCHYMAL STEM CELLS

T. Thangarajah, C. Pendegrass, S. Shahbazi, S. Lambert, S. Alexander, G. Blunn
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Abstract

Background Re-attachment of tendon to bone is challenging with surgical repair failing in up to 90% of cases. Poor biological healing is common and characterised by the formation of weak scar tissue. Previous work has demonstrated that decellularised allogenic demineralised bone matrix (DBM) regenerates a physiologic enthesis. Xenografts offer a more cost-effective option but concerns over their immunogenicity have been raised. We hypothesised that augmentation of a healing tendon-bone interface with DBM incorporated with autologous mesenchymal stem cells (MSCs) would result in improved function, and restoration of the native enthesis, with no difference between xenogenic and allogenic scaffolds. Methods Using an ovine model of tendon-bone retraction the patellar tendon was detached and a complete distal tendon defect measuring 1 cm was created. Suture anchors were used to reattach the shortened tendon and xenogenic DBM + MSCs (n=5) and allogenic DBM + MSCs (n=5) were used to bridge the defect. Functional recovery was assessed every 3 weeks and DBM incorporation into the tendon and its effect on enthesis regeneration was measured using histomorphometry. Results By 12 weeks, DBM augmentation resulted in significantly improved functional weight bearing with no failures in either group. Compared to xenogenic DBM, allogenic DBM was associated with significantly higher functional weight bearing at 6 (P=0.047), 9 (P=0.028) and 12 weeks (P=0.009). This was accompanied by a more direct type of enthesis characterised by significantly more fibrocartilage and mineralised fibrocartilage. Xenograft was also associated with an immunogenic reaction despite preoperative decellularisation. Conclusion This study shows that DBM enhances tendon-bone healing and may reduce the high failure rates associated with surgery. An immunogenic reaction, and inferior biomechanical and histological results were also associated with the use of xenograft. Allogenic DBM with autologous MSCs may be a suitable scaffold for the enhancement of tendon-bone healing in the clinical setting. Disclosures Funded by IKC PoC grant awarded by the University of Leeds Ethical approval Granted by the study institution (University College London)
利用脱矿骨基质和间充质干细胞进行肌腱再植
背景:肌腱与骨的再附着是具有挑战性的,手术修复失败率高达90%。生物愈合不良是常见的,其特点是形成脆弱的疤痕组织。以前的工作已经证明脱细胞异体脱矿骨基质(DBM)再生生理性内植。异种移植物提供了一种更具成本效益的选择,但对其免疫原性的担忧已经提出。我们假设用DBM结合自体间充质干细胞(MSCs)来增强愈合肌腱-骨界面,可以改善功能,并恢复原生端部,异种和同种异体支架之间没有区别。方法采用羊肌腱-骨缩回模型,分离髌骨肌腱,建立1 cm的远端肌腱缺损。使用缝合锚钉重新连接缩短的肌腱,并使用异种DBM + MSCs (n=5)和同种异体DBM + MSCs (n=5)桥接缺损。每3周评估一次功能恢复情况,并使用组织形态测量法测量DBM融入肌腱及其对肌腱端再生的影响。结果12周时,两组患者均未出现功能性负重失败。与异种DBM相比,同种异体DBM在第6周(P=0.047)、第9周(P=0.028)和第12周(P=0.009)时的功能体重显著增加。这伴随着一种更直接的内嵌类型,其特征是明显更多的纤维软骨和矿化纤维软骨。尽管术前脱细胞,异种移植物也与免疫原性反应相关。结论DBM可促进肌腱-骨愈合,降低手术后的高失败率。免疫原性反应和较差的生物力学和组织学结果也与异种移植物的使用有关。同种异体DBM与自体间充质干细胞可能是一种合适的支架,以促进肌腱-骨愈合在临床设置。由利兹大学授予的IKC PoC资助伦理批准由研究机构(伦敦大学学院)批准
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