Modified Hyaluronic Acid for Extrasynovial Tendon Graft

描述（由申请人提供）： 影响手功能的屈肌腱损伤在年轻人中很常见，并且经常导致严重的残疾。粘连的形成仍然是一个难题，导致屈肌腱修复后效果不佳。肌腱移植物在重建手指功能方面仍然起着非常重要的作用，无论是替换受损的肌腱还是延长健康的肌腱进行转移。临床上，虽然大多数肌腱移植物进入滑膜环境，肌腱系统包括滑膜衬里鞘，大多数肌腱移植物来自滑膜外肌腱来源。动物模型表明，滑膜外肌腱移植物与周围组织的粘连比滑膜内肌腱移植物更多。在先前的初步研究中，我们发现，与滑膜内肌腱相比，滑膜外肌腱具有粗糙的表面和更高的滑动阻力。虽然可以通过将透明质酸（HA）应用于肌腱表面来减少摩擦，但是由于HA与肌腱表面之间的弱结合，在重复运动后其效果减弱。此外，HA在组织中的半衰期很短。我们发现碳二亚胺衍生的HA（cd-HA）明胶增强了HA与肌腱表面的结合能力，降低了摩擦力，并增加了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。 为了验证这一假设，提出了以下具体目标：1）体外鉴定和量化经cd-HA明胶修饰的滑膜外肌腱的表面状态; 2）鉴定经cd-HA明胶处理的滑膜外肌腱移植后的体内滑动特性、粘连形成和愈合状态。如果这一假设得到支持，未来的研究可以调查这种对肌腱移植物滑动和粘连的影响的机制，以及使用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.