Large-scale bone defects caused by trauma, infection, or tumors severely threaten human health and quality of life. In clinical treatment, developing highly osteogenic scaffold materials based on in situ bone regeneration is an effective strategy for repairing large bone defects. From the perspective of energy supply and biosynthetic transformation, developing innovative biomaterials that drive anabolic metabolism to accelerate osteogenesis represents an emerging direction in bone tissue engineering and regeneration.

On September 5, the team led by Professor Zhang Peng from Shenzhen University of Advanced Technology, in collaboration with Professor Chen Guoqiang from Tsinghua University and Assistant Professor Zhang Xu from Peking University School of Stomatology, published a review article online in Trends in Biotechnology (Cell Press) titled “Metabolically activated energetic materials mediate cellular anabolism for bone regeneration.”

Screenshot of the published article

Using multi-omics sequencing, isotope tracing, and various animal models, the study elucidated the mechanism by which the bio-copolyester P(3HB-co-4HB) promotes bone regeneration. After implantation, P(3HB-co-4HB) degrades to release 3-hydroxybutyrate (3HB), an endogenous bioenergetic substrate that enhances cellular anabolism, boosts ATP production, and promotes osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) as well as capillary-like network formation by EA.hy926 cells.

Furthermore, 3HB is metabolized via the TCA cycle into citrate, which facilitates citrate-containing apatite synthesis during hBMSC osteogenic differentiation and ultimately incorporates as citrate into the natural components of newly formed bone. Based on these findings, the team proposed the academic concept of “metabolically activated energetic materials (MAM).” This framework facilitates the design and translational development of MAM materials tailored to regenerative metabolic microenvironments, offering new insights for regenerative medicine.

Research schematic

Professor Zhang Peng is the first corresponding author. Dr. Li Jian (assistant researcher at Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences), Professor Chen Guoqiang, and Assistant Professor Zhang Xu are co-corresponding authors. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, is the first affiliated institution. Professor Qin Ling from The Chinese University of Hong Kong provided constructive comments on the manuscript.

For industrial translation, Zhang Peng’s group has actively engaged with industry. The project has won the Third Prize in the 2021 “Entrepreneurship Star” Innovation Competition in Nanshan, Shenzhen, and the Excellence Award in the Second “Leading Cup” Future Technology Innovation Competition, demonstrating the strong translational potential and clinical prospects of this novel metabolically activated energetic materials. This work was supported by the National Natural Science Foundation of China (Major Research Plan Cultivation Project), key projects of Guangdong Province, and international cooperation projects of Shenzhen Science and Technology Innovation Commission.