Kartogenin/羟丙基纤维素复合涂层对PET韧带材料生物相容性和腱-骨愈合的影响及机制研究

The anterior cruciate ligament (ACL) reconstruction of knee after injury has always been one of the hot spots and focus in sports medicine research field. Many clinical studies have shown that the short-term safety and efficacy of ACL reconstruction using polyethylene terephthalate (PET) artificial ligament is satisfying, but long-term efficacy of postoperative is not good, because of the poor biological result of graft-bone healing. Our previous studies showed that hydrophilic hydroxypropylcellulose (HPC) coated on the surface of PET ligament could effectively induce the differentiation of osteoblasts. However, the effect of single coating is limited, and the effect of promoting tendon-bone healing in vivo is not stable. Recent studies have found that small molecule drug kartogenin (KGN) could effectively promote cartilage regeneration, induce collagen synthesis and cartilage-like tissue formation. Therefore, this study intends to interact the role of two kinds of coatings in order to prepare effective and sustained-release KGN/HPC composite coatings, and to study the effect of this composite coating on cell compatibility, osteogenic differentiation and graft-bone healing of PET material by cytology study in vitro and animal models of graft-bone healing in vivo, and to explore the related molecular mechanism. In this study, our aim is to successfully prepare effective KGN/HPC composite coating, and accelerate the healing rate of PET ligament graft-bone by using KGN/HPC composite coating on the surface of PET ligament. Finally,we hope this study could provide theoretical and experimental basis for further research and development of artificial ligament materials in accordance with clinical requirements.

膝前交叉韧带（ACL）损伤后选择何种移植物进行重建一直是运动医学研究的热点和焦点之一。临床研究显示使用聚对苯二甲酸乙二醇酯（PET）人工韧带重建ACL的中短期安全性及疗效较为满意，但术后长期疗效仍存在移植物与骨生物性愈合差的问题。我们前期研究表明在PET韧带材料表面涂覆亲水性羟丙基纤维素（HPC）可有效诱导成骨细胞分化，但单一涂层对体内腱-骨愈合的促进作用有限。近期研究发现小分子药物kartogenin（KGN）可有效促进软骨再生，诱导胶原蛋白合成及软骨样组织形成。因此本研究拟将二者的作用协同以制备有效的KGN/HPC复合涂层，通过体外细胞学和体内移植物-骨愈合动物模型来研究该复合涂层对PET材料细胞相容性、成骨分化及移植物-骨愈合的影响，探讨相关分子机制。本课题期望应用成功制备的KGN/HPC复合涂层能够促进PET韧带与骨的愈合，为进一步研制符合临床需求的人工韧带材料提供理论和实验依据。

膝关节前交叉韧带（ACL）损伤后选择何种移植物进行重建一直是运动医学研究的热点和焦点问题。目前临床广泛使用LARS人工韧带重建ACL，其材料为聚对苯二甲酸乙二醇酯（PET），临床中短期安全性及疗效较为满意，但术后长期疗效仍存在移植物与骨生物性愈合差的问题。前期研究表明在PET韧带材料表面涂覆羟丙基纤维素（HPC）可有效诱导成骨细胞分化。而其他研究发现小分子药物kartogenin（KGN）可有效促进软骨再生，诱导胶原蛋白合成及软骨样组织形成。因此本研究将二者的作用协同以制备有效的KGN/HPC复合涂层，通过体外细胞学和体内移植物-骨愈合动物模型来研究该复合涂层对PET材料细胞相容性、成骨分化及移植物-骨愈合的影响，探讨相关分子机制。本课题成功制备了HPC涂层和KGN/HPC复合涂层，但在后续的预实验（细胞实验）中，并未发现KGN/HPC复合涂层对细胞增殖和黏附起积极作用，并且实验结果还较单纯HPC涂层组更差，虽然经过不断地调整实验条件，依然未发现KGN/HPC复合涂层对细胞增殖和黏附的积极的作用。所以后续实验方案改为仅对PET组和HPC涂层组进行比格犬动物实验，实验结果显示HPC涂层能够促进PET韧带与骨的愈合。以上结果将为进一步研制符合临床需求的人工韧带材料提供理论和实验依据。