Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
Advanced Biomaterials and Tissue Engineering Centre, Huazhong University of Science and Technology, Wuhan 430074, China.
Sci Adv. 2020 Mar 25;6(13):eaay7608. doi: 10.1126/sciadv.aay7608. eCollection 2020 Mar.
Cellular bioenergetics (CBE) plays a critical role in tissue regeneration. Physiologically, an enhanced metabolic state facilitates anabolic biosynthesis and mitosis to accelerate regeneration. However, the development of approaches to reprogram CBE, toward the treatment of substantial tissue injuries, has been limited thus far. Here, we show that induced repair in a rabbit model of weight-bearing bone defects is greatly enhanced using a bioenergetic-active material (BAM) scaffold compared to commercialized poly(lactic acid) and calcium phosphate ceramic scaffolds. This material was composed of energy-active units that can be released in a sustained degradation-mediated fashion once implanted. By establishing an intramitochondrial metabolic bypass, the internalized energy-active units significantly elevate mitochondrial membrane potential (ΔΨm) to supply increased bioenergetic levels and accelerate bone formation. The ready-to-use material developed here represents a highly efficient and easy-to-implement therapeutic approach toward tissue regeneration, with promise for bench-to-bedside translation.
细胞生物能量学（CBE）在组织再生中起着关键作用。从生理学上讲，增强的代谢状态有利于合成代谢生物合成和有丝分裂，从而加速再生。然而，迄今为止，针对实质性组织损伤的 CBE 重编程方法的发展受到限制。在这里，我们表明，与商业化的聚乳酸（PLA）和磷酸钙陶瓷支架相比，在承重骨缺损的兔模型中使用生物能量活性材料（BAM）支架可大大增强诱导修复。这种材料由能量活性单元组成，一旦植入，这些能量活性单元可以以持续降解介导的方式释放。通过建立线粒体内部代谢旁路，内化的能量活性单元可显著提高线粒体膜电位（ΔΨm），以提供更高的生物能量水平并加速骨形成。这里开发的即用型材料代表了一种高效且易于实施的组织再生治疗方法，有望实现从实验室到临床的转化。
