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Aggrecan-like biomimetic proteoglycans (BPGs) composed of natural chondroitin sulfate bristles grafted onto a poly(acrylic acid) core for molecular engineering of the extracellular matrix
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2018-06-01 , DOI: 10.1016/j.actbio.2018.05.013
K. Prudnikova , S.E. Lightfoot Vidal , S. Sarkar , T. Yu , R.W. Yucha , N. Ganesh , L.S. Penn , L. Han , C.L. Schauer , E.J. Vresilovic , M.S. Marcolongo

Biomimetic proteoglycans (BPGs) were designed to mimic the three-dimensional (3D) bottlebrush architecture of natural extracellular matrix (ECM) proteoglycans, such as aggrecan. BPGs were synthesized by grafting native chondroitin sulfate bristles onto a synthetic poly(acrylic acid) core to form BPGs at a molecular weight of approximately ∼1.6 MDa. The aggrecan mimics were characterized chemically, physically, and structurally, confirming the 3D bottlebrush architecture as well as a level of water uptake, which is greater than that of the natural proteoglycan, aggrecan. Aggrecan mimics were cytocompatible at physiological concentrations. Fluorescently labeled BPGs were injected into the nucleus pulposus of the intervertebral disc ex vivo and were retained in tissue before and after static loading and equilibrium conditioning. BPGs infiltrated the tissue, distributed and integrated with the ECM on a molecular scale, in the absence of a bolus, thus demonstrating a new molecular approach to tissue repair: molecular matrix engineering. Molecular matrix engineering may compliment or offer an acellular alternative to current regenerative medicine strategies.

Statement of Significance

Aggrecan is a natural biomolecule that is essential for connective tissue hydration and mechanics. Aggrecan is composed of negatively charged chondroitin sulfate bristles attached to a protein core in a bottlebrush configuration. With age and degeneration, enzymatic degradation of aggrecan outpaces cellular synthesis resulting in a loss of this important molecule. We demonstrate a novel biomimetic molecule composed of natural chondroitin sulfate bristles grafted onto an enzymatically-resistant synthetic core. Our molecule mimics a 3D architecture and charge density of the natural aggrecan, can be delivered via a simple injection and is retained in tissue after equilibrium conditioning and loading. This novel material can serve as a platform for molecular repair, drug delivery and tissue engineering in regenerative medicine approaches.



中文翻译:

由天然硫酸软骨素刷毛组成的类Aggrecan仿生蛋白聚糖(BPG),接枝到聚(丙烯酸)核上用于细胞外基质的分子工程

仿生蛋白聚糖(BPG)旨在模拟天然细胞外基质(ECM)蛋白聚糖(如聚集蛋白聚糖)的三维(3D)牙刷架结构。通过将天然硫酸软骨素刷毛接枝到合成的聚(丙烯酸)核上以形成分子量约为1.6 MDa的BPG来合成BPG。对聚集蛋白聚糖的模拟物进行了化学,物理和结构表征,证实了3D洗瓶刷的结构以及吸水率,该水平大于天然蛋白聚糖聚集蛋白聚糖的吸水率。Aggrecan模拟物在生理浓度下具有细胞相容性。荧光标记BPGS注入椎间盘的髓核体外并在静态负载和平衡调节前后保留在组织中。BPG在没有大丸药的情况下渗透到组织中,并在分子尺度上与ECM结合并整合在一起,从而证明了一种新的组织修复分子方法:分子基质工程。分子基质工程可以补充当前的再生医学策略或提供无细胞替代方法。

重要声明

Aggrecan是一种天然生物分子,对于结缔组织的水合作用和力学至关重要。Aggrecan是由带负电的硫酸软骨素硬毛构成的,该硬毛以牙刷刷的形式附着在蛋白质核心上。随着年龄的增长和变性,聚集蛋白聚糖的酶促降解超过细胞合成,导致该重要分子的损失。我们展示了由天然硫酸软骨素硬毛嫁接到抗酶合成核心上的新型仿生分子。我们的分子模仿了天然软骨聚集蛋白聚糖的3D结构和电荷密度,可以通过简单的注射进行递送,并在平衡调节和加载后保留在组织中。这种新型材料可以作为再生医学方法中分子修复,药物输送和组织工程的平台。

更新日期:2018-06-01
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