Photocrosslinked natural hydrogel composed of hyaluronic acid and gelatin enhances cartilage regeneration of decellularized trachea matrix
Photocrosslinked natural hydrogel composed of hyaluronic acid and gelatin enhances cartilage regeneration of decellularized trachea matrix
复制标题
由透明质酸和明胶组成的光交联天然水凝胶增强脱细胞气管基质的软骨再生
DOI：
10.1016/j.msec.2020.111628
复制
发表时间：
2021-02-01
影响因子：
7.9
通讯作者：
Zhou, Guangdong
中科院分区：
文献类型：
--
作者：
Xu, Yong;Wang, Zongxin;Zhou, Guangdong
长段气管缺损的修复一直是临床上的一大挑战。解决这一问题的关键是开发一种理想的具有生物学功能的气管替代物。使用基于激光微孔技术（LDTM）的脱细胞气管基质证明了制备具有管状形状和令人满意的软骨再生的理想气管替代物用于组织工程气管再生的可能性。然而，由于LDTM的细胞粘附性很低，需要过高浓度的接种细胞，这极大地限制了其临床转化。为了解决这个问题，当前的研究提出了一种新策略，使用光交联天然水凝胶（PNH）载体来提高细胞保留效率并改善气管软骨再生。我们的结果表明，PNH 在紫外光下经历了快速的液固相转化。此外，PNH中的光生醛基可以快速与LDTM表面固有的氨基反应形成亚胺键，从而有效地将细胞-PNH复合物固定到LDTM表面和/或将复合物保持在LDTM微孔中。因此，PNH 显着提高了细胞接种效率，并在整个 LDTM 中实现了稳定的细胞保留和均匀的细胞分布。此外，PNH表现出优异的生物相容性和低细胞毒性，并提供天然的三维仿生微环境，有效促进软骨细胞的存活和增殖、细胞外基质的产生和软骨再生。最重要的是，在相对较低的细胞接种浓度下，均匀的管状软骨成功再生，具有准确的气管形状、足够的机械强度、良好的弹性、典型的腔隙结构和软骨特异性的细胞外基质沉积。我们的研究结果建立了一种用于各种组织再生的通用且有效的细胞接种策略，并为长段气管缺损的修复和功能重建提供了令人满意的气管替代品。
Repair of long segmental trachea defects is always a great challenge in the clinic. The key to solving this problem is to develop an ideal trachea substitute with biological function. Using of a decellularized trachea matrix based on laser micropore technique (LDTM) demonstrated the possibility of preparing ideal trachea substitutes with tubular shape and satisfactory cartilage regeneration for tissue-engineered trachea regeneration. However, as a result of the very low cell adhesion of LDTM, an overly high concentration of seeding cell is required, which greatly restricts its clinical translation. To address this issue, the current study proposed a novel strategy using a photocrosslinked natural hydrogel (PNH) carrier to enhance cell retention efficiency and improve tracheal cartilage regeneration. Our results demonstrated that PNH underwent a rapid liquid-solid phase conversion under ultraviolet light. Moreover, the photo-generated aldehyde groups in PNH could rapidly react with inherent amino groups on LDTM surfaces to form imine bonds, which efficiently immobilized the cell-PNH composite to the surfaces of LDTM and/or maintained the composite in the LDTM micropores. Therefore, PNH significantly enhanced cell-seeding efficiency and achieved both stable cell retention and homogenous cell distribution throughout the LDTM. Moreover, PNH exhibited excellent biocompatibility and low cytotoxicity, and provided a natural three-dimensional biomimetic microenvironment to efficiently promote chondrocyte survival and proliferation, extracellular matrix production, and cartilage regeneration. Most importantly, at a relatively low cell-seeding concentration, homogeneous tubular cartilage was successfully regenerated with an accurate tracheal shape, sufficient mechanical strength, good elasticity, typical lacuna structure, and cartilage-specific extracellular matrix deposition. Our findings establish a versatile and efficient cell-seeding strategy for regeneration of various tissue and provide a satisfactory trachea substitute for repair and functional reconstruction of long segmental tracheal defects.