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聚(3-羟基丁酸-co-3-羟基己酸)支架在大鼠模型中用于肌腱修复的应用。

The application of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds for tendon repair in the rat model.

机构信息

Guy Hilton Research Centre, Institute of Science and Technology in Medicine, Keele University, Stoke on Trent, ST4 7QB, UK.

出版信息

Biomaterials. 2013 Sep;34(28):6683-94. doi: 10.1016/j.biomaterials.2013.05.041. Epub 2013 Jun 13.

DOI:10.1016/j.biomaterials.2013.05.041
PMID:23768899
Abstract

Tendon injuries and defects present a substantial burden to global healthcare economies. There are no synthetic/biosynthesised implants available which can restore full function or match the mechanical properties of native tendon. Therefore, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was investigated for its utility as a scaffold in a rat Achilles tendon repair model. Porous PHBHHx tubes and fibres were prepared with particle leaching and extrusion methods, respectively. Collagen gels reinforced by polymer fibres were inserted into the lumen of scaffold tubes to create the operational scaffold unit. Mechanical testing demonstrated that PHBHHx scaffolds had comparable mechanical properties to rat tendon, with maximal loads of 23.73 ± 1.08 N, compared to 17.35 ± 1.76 N in undamaged rat Achilles tendon. Sprague-Dawley (SD) rats were split into four experimental groups: control, PHBHHx scaffold only, PHBHHx scaffold and collagen, PHBHHx scaffold, collagen and tenocyte compositions for implantation to repair an induced Achilles tendon defect. No secondary immune response to PHBHHx was observed over a 40 days period of implantation. Movement was restored in PHBHHx scaffold-collagen-tenocyte recipient rats at an earlier time point than in other experimental groups, with complete load-bearing and function returning 20 days post-surgery as determined by the Achilles Functional Index. In vitro testing of tendon constructs after 40 days demonstrated reductions in PHBHHx molecular weight and polydispersity index accompanied by an increase in mean chain length indicating degradation of smaller polymer chain subunits. Similarly a reduction in PHBHHx tube ultimate tensile strength and elastic modulus was observed. Histological analysis provided evidence of tissue remodelling and cell alignment. In summary, PHBHHx scaffolds have been successfully applied in an in vivo tendon repair model raising promise for future utility in tissue engineering applications.

摘要

肌腱损伤和缺陷给全球医疗保健经济带来了巨大负担。目前尚无可用的合成/生物合成植入物可以恢复全部功能或与天然肌腱的机械性能相匹配。因此,研究了聚(3-羟基丁酸-co-3-羟基己酸)(PHBHHx) 作为一种在大鼠跟腱修复模型中的支架的用途。通过颗粒浸出和挤出方法分别制备了多孔 PHBHHx 管和纤维。将聚合物纤维增强的胶原凝胶插入支架管的内腔中,以创建操作支架单元。机械测试表明,PHBHHx 支架具有与大鼠肌腱相当的机械性能,最大负载为 23.73 ± 1.08 N,而未受损的大鼠跟腱的最大负载为 17.35 ± 1.76 N。SD 大鼠分为四组进行实验:对照组、仅 PHBHHx 支架组、PHBHHx 支架和胶原组、PHBHHx 支架、胶原和肌腱细胞组成物植入以修复诱导的跟腱缺损。在植入的 40 天期间,未观察到对 PHBHHx 的二次免疫反应。在 PHBHHx 支架-胶原-肌腱细胞接受者大鼠中,运动更早得到恢复,与其他实验组相比,在手术后 20 天即可完全承受负荷和恢复功能,这可通过跟腱功能指数来确定。40 天后对肌腱构建体进行的体外测试表明,PHBHHx 分子量和多分散指数降低,平均链长增加,表明较小的聚合物链亚基降解。同样,观察到 PHBHHx 管的极限拉伸强度和弹性模量降低。组织学分析提供了组织重塑和细胞排列的证据。总之,PHBHHx 支架已成功应用于体内肌腱修复模型,为未来在组织工程应用中的应用带来了希望。

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