Modified Hyaluronic Acid for Extrasynovial Tendon Graft

描述(由申请人提供)： 屈肌腱损伤影响手功能在年轻人中很常见，并经常导致严重的残疾。粘连的形成仍然是一个难题，这导致屈肌腱修复后效果不佳。无论是修复受损的肌腱还是延长健康的肌腱以供移植，肌腱移植在重建手指功能方面仍发挥着非常重要的作用。临床上，虽然大多数肌腱移植物进入滑膜环境，即包括滑膜衬里的鞘的肌腱系统，但大多数肌腱移植物来自滑膜外肌腱来源。动物模型表明，滑膜外肌腱移植物比滑膜内肌腱移植物与周围组织有更多的粘连。在先前的先导性研究中，我们发现滑膜外肌腱表面粗糙，与滑膜内肌腱相比，滑膜外肌腱具有更高的抗滑移能力。虽然在肌腱表面应用透明质酸(HA)可以减少摩擦力，但由于HA与肌腱表面的结合较弱，其作用在重复运动后会减弱。此外，HA在组织中的半衰期很短。我们发现，HA(CD-HA)明胶的碳二亚胺衍生化增强了HA与肌腱表面的结合能力，减少了摩擦力，并延长了HA在体外组织中的半衰期。我们推测，CD-HA明胶可以改善肌腱移植物在体内的滑动能力和磨损效果，从而减少粘连的形成。 为了验证这一假说，提出了以下具体目标：1)在体外鉴定和定量CD-HA明胶修饰的滑膜外肌腱的表面状态；2)在体内鉴定CD-HA明胶处理的滑膜外肌腱移植后的滑动特性、粘连形成和愈合状态。如果这一假说得到支持，未来的研究可以探索这种影响肌腱移植物滑动和粘连的机制，并利用CD-HA明胶作为载体将抗炎或生长因子携带到肌腱表面，以提高肌腱移植物愈合的质量。

DESCRIPTION (provided by applicant): Flexor tendon injuries affecting hand function are common in young adults, and frequently result in significant disability. Adhesion formation continues to be a difficult problem, which leads a poor outcome after flexor tendon repairs. The tendon graft still plays a very important role in reconstruction to restore finger function, either to replace a damaged tendon or to lengthen a healthy tendon for transfer. Clinically, although most tendon grafts go into a synovial environment i.e., a tendon system that includes a synovially lined sheath, most tendon grafts come from extrasynovial tendon sources. Animal models have shown that extrasynovial tendon grafts are associated with more adhesions to the surrounding tissue than intrasynovial tendon grafts. In the previously pilot study, we found that extrasynovial tendon has a rough surface and higher gliding resistance compared to intrasynovial tendon. Although friction can be reduced with the application of hyaluronic acid (HA) applied to the tendon surface, its effect is diminished after repetitive motion because of weak binding between HA and the tendon surface. Furthermore, the half-life of HA in tissues is short. We have found that carbodiimide derivatization of HA (cd-HA) gelatin enhances the binding ability of HA to the tendon surface, decreases the friction, and increase the half-life of HA in tissues in vitro. We hypothesize that cd-HA gelatin can improve the gliding ability and the abrasion effect of tendon grafts in vivo, and thereby decreasing adhesion formation. In order to test this hypothesis, the following specific aims are proposed: 1) To identify and quantify the surface status of extrasynovial tendon modified by cd-HA gelatin in vitro, 2) To identify the gliding characteristics, adhesion formation, and healing status in vivo after tendon grafting with an extrasynovial tendon treated by the cd-HA gelatin. If the hypothesis is supported, future studies can investigate the mechanisms by which this effect on tendon graft gliding and adhesions is achieved, and the use of cd-HA gelatin as a vehicle to carry anti-inflammatory or growth factors to the tendon surface, to improve the quality of tendon graft healing.