Advanced bioactive glue tethering Lubricin/PRG4 to promote integrated healing of avascular meniscus tears.
Advanced bioactive glue tethering Lubricin/PRG4 to promote integrated healing of avascular meniscus tears.
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DOI：
10.1016/j.bioactmat.2023.04.026
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发表时间：
2023-10
影响因子：
18.9
通讯作者：
Lee, Chang H.
中科院分区：
文献类型：
--
作者：
Tarafder, Solaiman;Ghataure, Jaskirti;Langford, David;Brooke, Rachel;Kim, Ryunhyung;Eyen, Samantha Lewis;Bensadoun, Julian;Felix, Jeffrey T.;Cook, James L.;Lee, Chang H.
半月板损伤极为常见，仅在美国每年就有大约一百万患者接受手术治疗，但不存在再生疗法。此前，我们表明，通过基于纤维蛋白的生物胶控制应用结缔组织生长因子（CTGF）和转化生长因子β3（TGFβ3）可通过诱导滑膜间充质干/祖细胞的募集和逐步分化来促进半月板愈合。在这里，我们首先探索了京尼平（一种天然交联剂）在增强纤维蛋白胶的机械和降解性能方面的潜力。与此同时，我们确定了润滑素对半月板愈合的有害影响，并研究了润滑素在受伤的半月板表面沉积的机制。我们发现撕裂的半月板表面上透明质酸（HA）的预沉积介导了润滑素沉积。然后，我们对生物活性胶进行了肝素结合和 CD44 的化学修饰，以实现润滑素预涂半月板组织的牢固初始粘合和整合。我们的数据表明，肝素结合显着增强了润滑素涂层的半月板组织。同样，CD44对润滑素和透明质酸（HA）表现出很强的结合亲和力，进一步改善了HA/润滑素预涂半月板损伤的综合愈合。这些发现可能为开发指导半月板损伤再生愈合的转化生物活性胶奠定了重要基础。我们展示了最佳京尼平交联，以促进半月板愈合生物活性胶的物理特性。临床相关的润滑素渗入半月板损伤显示出对半月板愈合的有害影响。肝素的化学修饰实现了润滑素预涂半月板组织的牢固结合和整合。 CD44与润滑素和透明质酸（HA）表现出很强的结合亲和力，进一步改善了组织整合。这些发现为转化生物活性胶半月板再生奠定了重要基础。
Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone, but no regenerative therapy exist. Previously, we showed that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) via fibrin-based bio-glue facilitate meniscus healing by inducing recruitment and stepwise differentiation of synovial mesenchymal stem/progenitor cells. Here, we first explored the potential of genipin, a natural crosslinker, to enhance fibrin-based glue's mechanical and degradation properties. In parallel, we identified the harmful effects of lubricin on meniscus healing and investigated the mechanism of lubricin deposition on the injured meniscus surface. We found that the pre-deposition of hyaluronic acid (HA) on the torn meniscus surface mediates lubricin deposition. Then we implemented chemical modifications with heparin conjugation and CD44 on our bioactive glue to achieve strong initial bonding and integration of lubricin pre-coated meniscal tissues. Our data suggested that heparin conjugation significantly enhances lubricin-coated meniscal tissues. Similarly, CD44, exhibiting a strong binding affinity to lubricin and hyaluronic acid (HA), further improved the integrated healing of HA/lubricin pre-coated meniscus injuries. These findings may represent an important foundation for developing a translational bio-active glue guiding the regenerative healing of meniscus injuries. We demonstrated an optimal genipin cross-linking to promote physical properties of bioactive glue for meniscus healing. Clinically relevant lubricin infiltration into meniscus injuries showed harmful effect on integrated meniscus healing. Chemical modifications with heparin achieved a strong bonding and integration of lubricin pre-coated meniscal tissues. CD44, exhibiting a strong binding affinity to lubricin and hyaluronic acid (HA), further improved the tissue integration . These findings represent an important foundation for a translational bio-active glue meniscus regeneration.
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影响因子：
2.8
作者：
Jones, Aled R. C.;Gleghorn, Jason P.;Flannery, Carl R.
通讯作者：
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作者：
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