Adjusting the stiffness of a cell-free hydrogel system based on tissue-specific extracellular matrix to optimize adipose tissue regeneration.
Adjusting the stiffness of a cell-free hydrogel system based on tissue-specific extracellular matrix to optimize adipose tissue regeneration.
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DOI：
10.1093/burnst/tkad002
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发表时间：
2023
期刊：
影响因子：
5.3
通讯作者：
Lu, Feng
中科院分区：
文献类型：
--
作者：
Li, Ye;Bi, Xin;Wu, Mengfan;Chen, Xinyao;Zhan, Weiqing;Dong, Ziqing;Lu, Feng
大面积软组织缺损的修复具有挑战性。临床治疗方法受到与供体部位损伤相关的问题和需要多次外科手术的阻碍。尽管脱细胞脂肪组织（DAT）的出现为这些问题提供了新的解决方案，但不能实现最佳的组织再生效率，因为DAT的硬度不能通过调节其浓度在体内改变。本研究旨在通过物理改变DAT的刚度来提高脂肪再生的效率，以更好地修复大体积软组织缺损。在这项研究中，我们形成了三种不同的无细胞水凝胶系统物理交联DAT与不同浓度的甲基纤维素（MC; 0.05，0.075和0.10 g/ml）。无细胞水凝胶系统的刚度可以通过改变MC的浓度来调节，并且所有三种无细胞水凝胶系统都是可注射和可模塑的。随后，将无细胞水凝胶系统移植到裸鼠背部。在第3、7、10、14、21和30天进行移植物脂肪形成的组织学、免疫荧光和基因表达分析。在第7、14和30天，0.10 μ g/ml组的脂肪源性干细胞（ASC）迁移和血管化高于0.05和0.075 μ g/ml组。值得注意的是，在第7、14和30天，0.075 μ g/ml组中ASC的脂肪形成和脂肪再生显著高于0.05 μ g/ml组（p < 0.01或p < 0.001）和0.10 μ g/ml组（p < 0.05或p < 0.001）。通过与MC的物理交联来调节DAT的刚度，可以有效促进脂肪再生，这对开发有效修复和重建大体积软组织缺损的方法具有重要意义。
Large-area soft tissue defects are challenging to reconstruct. Clinical treatment methods are hampered by problems associated with injury to the donor site and the requirement for multiple surgical procedures. Although the advent of decellularized adipose tissue (DAT) offers a new solution to these problems, optimal tissue regeneration efficiency cannot be achieved because the stiffness of DAT cannot be altered in vivo by adjusting its concentration. This study aimed to improve the efficiency of adipose regeneration by physically altering the stiffness of DAT to better repair large-volume soft tissue defects. In this study, we formed three different cell-free hydrogel systems by physically cross-linking DAT with different concentrations of methyl cellulose (MC; 0.05, 0.075 and 0.10 g/ml). The stiffness of the cell-free hydrogel system could be regulated by altering the concentration of MC, and all three cell-free hydrogel systems were injectable and moldable. Subsequently, the cell-free hydrogel systems were grafted on the backs of nude mice. Histological, immunofluorescence and gene expression analyses of adipogenesis of the grafts were performed on days 3, 7, 10, 14, 21 and 30. The migration of adipose-derived stem cells (ASCs) and vascularization were higher in the 0.10 g/ml group than in the 0.05 and 0.075 g/ml groups on days 7, 14 and 30. Notably, on days 7, 14 and 30, the adipogenesis of ASCs and adipose regeneration were significantly higher in the 0.075 g/ml group than in the 0.05 g/ml group (p < 0.01 or p < 0.001) and 0.10 g/ml group (p < 0.05 or p < 0.001). Adjusting the stiffness of DAT via physical cross-linking with MC can effectively promote adipose regeneration, which is of great significance to the development of methods for the effective repair and reconstruction of large-volume soft tissue defects.
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