The Use of Genipin as an Effective, Biocompatible, Anti-Inflammatory Cross-Linking Method for Nerve Guidance Conduits
The Use of Genipin as an Effective, Biocompatible, Anti-Inflammatory Cross-Linking Method for Nerve Guidance Conduits
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DOI：
10.1002/adbi.201900212
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发表时间：
2020-02-06
影响因子：
4.1
通讯作者：
O'Brien, Fergal J.
中科院分区：
文献类型：
--
作者：
Koci, Zuzana;Sridharan, Rukmani;O'Brien, Fergal J.
许多天然高分子生物材料为基础的神经导管（NGC）的开发，以促进周围神经损伤的修复。交联确保了NGC的机械完整性和所需的降解性能;然而，常见的方法如甲醛与细胞毒性有关。因此，存在对替代无毒交联剂的未满足的临床需求。在这项研究中，胶原蛋白为基础的NGCs与胶原蛋白/硫酸软骨素管腔填料用于研究的影响，交联的机械和结构性能，降解，生物相容性，和免疫反应。通过在冷冻干燥NGC之前将京尼平掺入溶液中，开发了京尼平交联的简化制造方法。这导致成功的交联，如通过京尼平交联导管与甲醛交联导管相比具有更高的交联度和相似的拉伸强度所证明的。京尼平交联还保留了通过扫描电子显微镜和光谱分析观察到的NGC宏观和微观结构。最重要的是，体外细胞研究表明，京尼平，不像甲醛交联的导管，支持雪旺细胞的活力。此外，京尼平交联的管道引导巨噬细胞远离促炎症状态并进入促修复状态。总体而言，京尼平被证明是一种有效的，安全的，生物相容的，和抗炎的替代甲醛交联临床级NGC。
A number of natural polymer biomaterial-based nerve guidance conduits (NGCs) are developed to facilitate repair of peripheral nerve injuries. Cross-linking ensures mechanical integrity and desired degradation properties of the NGCs; however, common methods such as formaldehyde are associated with cellular toxicity. Hence, there is an unmet clinical need for alternative nontoxic cross-linking agents. In this study, collagen-based NGCs with a collagen/chondroitin sulfate luminal filler are used to study the effect of cross-linking on mechanical and structural properties, degradation, biocompatibility, and immunological response. A simplified manufacturing method of genipin cross-linking is developed, by incorporating genipin into solution prior to freeze-drying the NGCs. This leads to successful cross-linking as demonstrated by higher cross-linking degree and similar tensile strength of genipin cross-linked conduits compared to formaldehyde cross-linked conduits. Genipin cross-linking also preserves NGC macro and microstructure as observed through scanning electron microscopy and spectral analysis. Most importantly, in vitro cell studies show that genipin, unlike the formaldehyde cross-linked conduits, supports the viability of Schwann cells. Moreover, genipin cross-linked conduits direct macrophages away from a pro-inflammatory and toward a pro-repair state. Overall, genipin is demonstrated to be an effective, safe, biocompatible, and anti-inflammatory alternative to formaldehyde for cross-linking clinical grade NGCs.