Wu Min, Zhao Yitao, Tao Meihan, Fu Meimei, Wang Yue, Liu Qi, Lu Zhihui, Guo Jinshan
Department of Histology and Embryology, GDMPA Key Laboratory of Key Technologies for Cosmetics Safety and Efficacy Evaluation, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, P. R. China.
Regenerative Medicine and Tissue Repair Research Center, Huangpu Institute of Materials, Guangzhou 511363, P. R. China.
ACS Appl Mater Interfaces. 2023 Nov 8;15(44):50836-50853. doi: 10.1021/acsami.3c09394. Epub 2023 Oct 30.
The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.
细胞生物能量学的最新进展揭示了将化学能转化为生物能用于治疗应用的潜力。尽管付出了诸多努力，但能够诱导长期生物能量效应并促进组织再生的三维（3D）支架仍然是一个巨大的挑战。在此，证明了三羧酸（TCA）循环的重要中间体L-苹果酸促进细胞能量代谢的能力，并通过L-苹果酸与脂肪族二醇的简易一锅法缩聚合成聚（二醇L-苹果酸）（PDoM）预聚物，随后进行支架制备和热交联，制备了一系列生物能量多孔支架。所开发的PDoM支架的降解产物可通过进入线粒体并参与TCA循环来调节代谢微环境，从而提高细胞内三磷酸腺苷（ATP）水平，进而促进细胞生物合成，包括I型胶原蛋白（Col1a1）、纤连蛋白1（Fn1）和肌动蛋白α2（Acta2/α-Sma）的产生。多孔PDoM支架被证明能够支持共培养的间充质干细胞（MSCs）的生长，并促进其分泌生物活性分子[如血管内皮生长因子（VEGF）、转化生长因子-β1（TGF-β1）和碱性成纤维细胞生长因子（bFGF）]，并且这种负载干细胞的支架结构被证明能够加速大鼠全层皮肤关键缺损模型中的伤口愈合。
