Engineering Tendon Grafts for Better Outcomes

工程肌腱移植以获得更好的结果

• 批准号: 8056142
• 负责人: Chunfeng Zhao
• 金额: $ 32.64万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-07 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056142
• 关键词: Accident and Emergency department; Accounting; Adhesions; Adhesives; Allografting; Animal Model; Autologous Transplantation; Beds; Biological Preservation; Canis familiaris; Carbodiimides; Cicatrix; Clinical; Digit structure; Engineering; Fingers; Flexor; Future; Glycoproteins; Goals; Hand; Hand Injuries; Hand functions; In Vitro; Injury; Laceration; Length; Lubrication; Methods; Modeling; Modification; Mucinous; Operative Surgical Procedures; Outcome; Pilot Projects; Play; Postoperative Period; Preparation; Prevention; Procedures; Property; Research Proposals; Role; Rotator Cuff; Rupture; Source; Surface; Surgeon; System; Tendon Injuries; Tendon structure; Testing; Time; Tissues; Translations; Trauma; Visit; Work; clinically relevant; falls; improved; in vivo; in vivo Model; lubricin; novel; public health relevance; reconstruction; repaired; restoration

DESCRIPTION (provided by applicant): Flexor tendon injury is a common and disabling clinical problem. If the damaged tendon cannot be immediately and directly repaired or primary repairs fail, a tendon graft is indicated. However, clinical outcomes have demonstrated high rates of complications after tendon graft, with adhesion formation and poor digit function. Clinical and animal models have shown that intrasynovial autografts provide better results than extrasynovial autografts, but clinical sources of intrasynovial tendons for use as tendon autografts are limited. Although our previous work has shown that an engineered extrasynovial graft surface, modified with carbodiimide derivatized HA (cd-HA), results in improved tendon gliding and decreased postoperative adhesions, resulting digit function still falls far short of normal. While allograft sources using intrasynovial tendon are possible, procedures used for allograft preparation and preservation damage the tendon surface and decrease its gliding ability. Encouragingly, our recent pilot studies have shown that surface treatment with cd-HA improved intrasynovial allograft frictional properties and decreased adhesion formation. More encouragingly, these improvements were noted even when the treated allografts were used in a scarred tendon bed, a much more clinically relevant model than the usual animal model used to study flexor tendon reconstruction, i.e., a normal, previously unoperated digit. More recently, we have developed a new compound for tendon surface modification by adding lubricin, a mucinous glycoprotein, to the cd-HA (cd-HA-lubricin). Our preliminary studies in vitro have shown that cd-HA-lubricin further improves the lubrication of extrasynovial tendon to a level comparable to intrasynovial tendon. Our overall goal is to develop a clinically applicable tendon graft alternative, an engineered allograft with a surface lubricated with cd-HA-lubricin that could become an off-the-shelf, functionally superior alternative to conventional tendon grafting. Given the known anti-adhesive properties of lubricin, we hypothesize that outcomes better than conventional extrasynovial autografting can be achieved with cd-HA-lubricin treated allografts in vivo. If our goals are achieved and the cd-HA-lubricin modified graft provides superior outcomes, clinical translation studies will be proposed in the future. We will also be able to use our novel engineered surface modification to study other applications of tendon grafting where adhesion prevention is important, such as for the rotator cuff. PUBLIC HEALTH RELEVANCE: The restoration of normal hand function is crucial after flexor tendon injuries, and tendon reconstruction plays an important role to achieve this goal. Unfortunately, poor tendon reconstruction results have challenged hand surgeons for over a half century. This research proposal is to develop a novel method for engineering tendon surfaces to improve the outcomes of tendon reconstruction leading towards restoration of normal hand function.

描述（由申请人提供）：屈肌腱损伤是一种常见且致残的临床问题。如果受损肌腱不能立即直接修复或初次修复失败，则需要进行肌腱移植。然而，临床结果表明，肌腱移植后并发症的发生率很高，包括粘连形成和手指功能不良。临床和动物模型表明，滑膜内自体移植物比滑膜外自体移植物提供更好的结果，但用作自体肌腱移植物的滑膜内肌腱的临床来源有限。尽管我们之前的工作表明，用碳二亚胺衍生化HA（cd-HA）修饰的工程化滑膜外移植物表面可以改善肌腱滑动并减少术后粘连，但最终的手指功能仍然远远低于正常水平。虽然使用滑膜内肌腱的同种异体移植物来源是可能的，但用于同种异体移植物准备和保存的程序会损伤肌腱表面并降低其滑动能力。令人鼓舞的是，我们最近的试点研究表明，用 cd-HA 进行表面处理可改善滑膜内同种异体移植物的摩擦特性并减少粘连形成。更令人鼓舞的是，即使在疤痕肌腱床中使用经过处理的同种异体移植物时，也注意到了这些改善，这是一种比用于研究屈肌腱重建的常用动物模型（即正常的、以前未手术的手指）更具临床相关性的模型。最近，我们通过在 cd-HA (cd-HA-lubricin) 中添加润滑素（一种粘液糖蛋白），开发了一种用于肌腱表面修饰的新化合物。我们的体外初步研究表明，cd-HA-lubricin 进一步改善滑膜外肌腱的润滑，达到与滑膜内肌腱相当的水平。我们的总体目标是开发一种临床适用的肌腱移植替代品，一种表面用 cd-HA-lubricin 润滑的工程同种异体移植物，可以成为一种现成的、功能优越的传统肌腱移植替代品。鉴于lubricin已知的抗粘连特性，我们假设体内用cd-HA-lubricin处理的同种异体移植物可以获得比传统滑膜外自体移植更好的结果。如果我们的目标得以实现，并且 cd-HA-lubricin 修饰的移植物能够提供优异的结果，那么未来将提出临床转化研究。我们还将能够使用我们新颖的工程表面改性来研究肌腱移植的其他应用，其中预防粘连很重要，例如肩袖。 公众健康相关性：屈肌腱损伤后手部正常功能的恢复至关重要，肌腱重建对于实现这一目标发挥着重要作用。不幸的是，半个多世纪以来，肌腱重建结果不佳一直困扰着手外科医生。本研究计划旨在开发一种工程肌腱表面的新方法，以改善肌腱重建的结果，从而恢复正常的手部功能。