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首页> 外文会议>World biomaterials congress >Biomimetic aggrecan molecularly engineers articular cartilage fallowing intra-articular injection in an OA rabbit model in vivo: a pilot study
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Biomimetic aggrecan molecularly engineers articular cartilage fallowing intra-articular injection in an OA rabbit model in vivo: a pilot study

机译：仿生聚集蛋白聚糖分子工程学在体内OA兔模型中进行关节腔内休假的关节软骨：一项初步研究

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Introduction: Several biomolecules are depleted in osteoarthritis (OA) including hyaluronic acid (HA) in the synovial fluid and aggrecan in articular cartilage. Intra-articular HA injections have been widely used in an attempt to restore joint lubrication and reduce cartilage erosion, however they have had limited success. Our lab has synthesized a novel biomimetic aggrecan (BA) aimed to infiltrate and distribute In articular cartilage delivered via an intra-articular injection'2'. BA mimics the 3-D bottle brush structure and properties of naturally occurring aggrecan and consists of a poly(acrylic acid) (10kDa) core with chondroitin sulfate bristles. BA is intended to restore hydration and mechanical function to arthritic cartilage by molecularly engineering tissue without relying on cellular synthesis to regenerate the extracellular matrix. Here we investigate the effect of intra-articular injections of BA into normal and arthritic rabbit knee joints by determining the histological response of articular cartilage to BA and quantifying the coefficient of friction of the rabbit knee joint. Materials and Methods: ACL Transection (ACLT) was used to create osteoarthritis in the right hindlimb of 4 female New Zealand white rabbits while the left hindlimb served as a control (IACUC approved pilot study). These rabbits formed 2 groups: 1) ACLT and 2) ACLT + BA. Five weeks after surgery, the two rabbits in the ACLT+ BA group underwent weekly injections of BA for 3 weeks. Two additional non-ACLT rabbits underwent BA injections in the right hindlimb once weekly for 3 weeks. The contralateral hindlimb of these two rabbits had one injection of fluorescently-labeled BA two days prior to sacrifice. Immediately after euthanasia, the limbs were tested in a custom pendulum friction tester to measure joint friction and then prepared for histology or fluorescent imaging. Results: Osteoarthritic rabbit knees treated with BA exhibited a lower coefficient of friction than OA knees alone. The rabbit knees which only received BA injections exhibited almost the same coefficient as the control knees. A more robust articular cartilage layer is present in arthritic specimens treated with BA than arthritic specimens with no treatment. Confocal microscopy of fluorescently labeled BA injected knees showed fluorescence within the articular cartilage. Discussion: The results from our pilot study provide preliminary data to support the ability of biomimetic aggrecan to molecularly engineer osteoarthritic cartilage through cartilage. Our preliminary findings on joint friction indicate that BA has no adverse effect on joint coefficient of friction and may help to reverse the increased friction that resulted from OA. A study using the same model is currently underway with a group size of five. Conclusion: Our pilot results indicate that BA decreases the coefficient of friction of the osteoarthritic knee and increases the cellularity and thickness of the articular cartilage, supporting our hypothesis that BA can provide increased hydration to the joint and regenerate superficial layers of articular cartilage.
机译：简介：骨关节炎（OA）中消耗了几种生物分子，其中包括滑液中的透明质酸（HA）和关节软骨中的聚集蛋白聚糖。关节内HA注射已广泛用于恢复关节润滑和减少软骨侵蚀的尝试，但是，其成功率有限。我们的实验室合成了一种新型仿生聚集蛋白聚糖（BA），旨在通过关节内注射“ 2”渗透并分布在关节软骨中。 BA模仿3-D奶瓶刷的结构和天然聚集蛋白聚糖的特性，并由带有硫酸软骨素硬毛的聚（丙烯酸）（10kDa）核组成。 BA旨在通过分子工程改造组织来恢复关节炎软骨的水合作用和机械功能，而无需依靠细胞合成来再生细胞外基质。在这里，我们通过确定关节软骨对BA的组织学反应并量化兔膝关节的摩擦系数，来研究将BA关节内注射到正常和关节炎兔膝关节中的效果。材料和方法：采用ACL横切术（ACLT）在4只雌性新西兰大白兔的右后肢中制造骨关节炎，而左后肢作为对照（IACUC批准的先导研究）。这些兔子分成两组：1）ACLT和2）ACLT + BA。手术后五周，ACLT + BA组的两只兔子每周进行BA注射3周。每周另对两只非ACLT兔右后肢进行BA注射，持续3周。这两只兔子的对侧后肢在处死前两天注射荧光标记的BA。安乐死后，立即在定制的摆摩擦测试仪中测试四肢，以测量关节摩擦，然后准备进行组织学或荧光成像。结果：BA治疗的骨关节炎兔膝关节的摩擦系数比单独的OA膝关节低。仅接受BA注射的兔膝部的系数几乎与对照膝部相同。与未经处理的关节炎标本相比，经BA处理的关节炎标本中存在更坚固的关节软骨层。荧光标记的BA注射的膝盖的共聚焦显微镜检查显示关节软骨内的荧光。讨论：我们的初步研究结果提供了初步数据，以支持仿生聚集蛋白聚糖通过软骨分子工程化骨关节炎软骨的能力。我们对关节摩擦的初步发现表明，BA对关节摩擦系数没有不利影响，并且可能有助于逆转OA导致的摩擦增加。目前正在使用一组相同的模型进行研究，每组五个人。结论：我们的试验结果表明，BA降低了骨关节炎膝盖的摩擦系数，并增加了关节软骨的细胞性和厚度，支持了我们的假设，即BA可以为关节提供更多的水合作用并再生关节软骨的浅层。

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