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）：屈肌肌腱损伤是常见且残疾的临床问题。如果无法立即并直接修复受损的肌腱或失败，则指示肌腱移植物。然而，临床结果表明肌腱移植后的并发症发生率很高，形成粘附和数字功能差。临床和动物模型表明，实际上的自体移植物比外膜外自体移植提供了更好的结果，但是作为肌腱自体移植的临床内膜肌腱的临床来源受到限制。尽管我们以前的工作表明，用碳二二胺衍生化的HA（CD-HA）修饰的工程外静脉外移植表面会导致肌腱滑动和术后粘附的降低，因此数字功能仍然远远远远远远超过正常状态。虽然可以使用内膜内肌腱的同种异体源来源，但用于同种异体移植准备和保存损害肌腱表面并降低其滑动能力的过程。令人鼓舞的是，我们最近的初步研究表明，用CD-HA进行表面处理改善了神经膜内的同种异体移植摩擦特性并减少了粘附形成。更令人鼓舞的是，即使在疤痕床床中使用了处理过的同种异体移植物，这是一个比临床相关的模型要比用于研究屈肌肌腱重建的常规动物模型的模型更为临床相关的模型，即正常的，以前无手术的数字。最近，我们通过在CD-HA（CD-HA-巴林）中添加润滑剂（粘液糖蛋白），开发了一种用于肌腱表面修饰的新化合物。我们在体外的初步研究表明，CD-HA-巴林蛋白将外膜肌腱的润滑进一步提高到与鞘膜内肌腱相当的水平。我们的总体目标是开发一种临床上适用的肌腱移植替代品，这是一种具有CD-HA-鲁布蛋白表面润滑的同种异体移植物，它可能成为现成的，在功能上优于常规肌腱移植的替代方案。鉴于润滑剂的已知抗粘附特性，我们假设可以通过在体内使用CD-HA-巴林治疗的同种异体移植来实现比常规外静脉化自身疗法更好的结果。如果实现我们的目标，并且CD-HA-巴林修饰的移植物可提供卓越的结果，将来将提出临床翻译研究。我们还将能够使用我们的新型工程表面修饰来研究肌腱移植的其他应用，而预防粘附很重要，例如肩袖。 公共卫生相关性：在屈肌肌腱受伤后，正常手部功能的恢复至关重要，并且肌腱重建在实现这一目标方面起着重要作用。不幸的是，不良的肌腱重建结果挑战了半个多世纪的手部外科医生。该研究建议是为工程肌腱表面开发一种新的方法，以改善肌腱重建的结果，从而恢复正常手部功能。