Professor Rongrong Zhu is Permanent Distinguished Professor, National Distinguished Young Scholars of China, doctoral supervisor, the deputy executive Director of the Key Laboratory of Spinal Cord Injury Regeneration and Repair of the Ministry of Education, the deputy director of the Aging and Cognitive Disorders Branch of Shanghai Society of Aging and Degenerative Diseases, the director of Shanghai Society of Biochemistry and Molecular Biology, the member of the Neuroprotection Group of the Neuroregeneration and Repair Professional Committee of Chinese Society of Research Hospitals, and the International Chinese Society of Osteology Lifetime member of ICMRS, member of Basic Youth College Group of Chinese Medical Doctor Association, editorial board of Biomedical Materials and other magazines. Pro. Zhu has presided over more than 10 national, provincial and ministerial level projects. Prof. Zhu won the Shanghai Young Scientific and Technological Talents, the second prize of Raisman Youth Forum of International Neuroprosthetics Society, Shanghai Chenguang Scholar, the second Prize of Basic Youth Research of Orthopaedic Academy of Chinese Medical Association, the first prize of Shanghai Natural Science Award, the first prize of Science and Technology Award of Chinese Rehabilitation Medical Association, the first prize of Huaxia Medical Science and Technology Award, and the Achievement Promotion Award of Shanghai Medical Science and Technology Award.

Prof. Zhu focus on the research of Biomaterials and nerve regeneration. In recent years, research group of Prof. Zhu has published more than 80 papers in authoritative journals, including Nat. Commun., Adv. Mater., Adv Sci., Acs Nano., Research, Biomaterials. Research group of Prof. Zhu has obtained two authorized patents in the United States, nine Chinese invention patents, and the innovative bioactive material for spinal cord injury repair and DeepScreen technologies have received PCT international patents and entered the U.S. national stage.

Topic title: Biomaterials for stem cell fate regulation and neuro-organoid construction

Abstract:

In the realm of tissue regeneration, stem cell-based treatments hold vast clinical promise. The maintenance of stem cell pluripotency and the efficient induction of lineage-specific differentiation are pivotal for ensuring their therapeutic efficacy. Harnessing the potential of bioactive materials to manipulate stem cell fate and construct organoid has emerged as a focal point of research and a critical avenue for innovative breakthroughs.

Our research has recently devised a high-throughput AI framework termed DeepScreen. We successfully trained a classification model that can accurately forecast the fate of neural stem cell differentiation by convolutional neural networks. The resultant DeepScreen platform represents an all-encompassing, intelligent high-throughput screening system that readily accommodates diverse neurotrophic factors, biomaterials, and biomaterial-factor combinatorial arrangements. By streamlining and expediting the screening and identification of novel therapeutics pertaining to neural protection and regeneration, it possesses the potential to achieve significant advancements in the field of biomaterial-guided stem cell fate modulation and central nervous system regeneration research.

Based on this AI screening system, we designed and validated investigated the influence of layered double hydroxide (LDH) materials, constructed with varying compositions of different metal elements, on the self-renewal and differentiation capabilities of various stem cells, along with the underlying molecular mechanisms. Previous research has shown that the addition of Mg/Al-LDH during the proliferation culture of mouse embryonic stem cells (mESCs) enhances their self-renewal capacity. Additionally, the different particle sizes of LDH have varying effects on mESC self-renewal. Treating mESCs with LDH composed of different cations, transcriptomic and proteomic screening revealed that compared to Mg/Al-LDH, Mg/Fe-LDH more effectively activates the LIF/PI3K/AKT signaling pathway. Subsequently, it activates downstream TET1/2 and promotes DNA demethylation processes in mESCs. Recent studies have demonstrated that LDH optimized with specific elemental ions enhances chondrogenic differentiation of human mesenchymal stem cells (hMSCs) and activates the Focal adhesion signaling pathway. Based on the above researches, we focus on the construction of engineered spinal cord organoids (enTsOrg) using LDH. enTsOrg exhibits the precise structure and cellular composition of the thoracic spinal cord segment and participates in axon regeneration and functional recovery in a complete SCI animal model.

In summary, our research focuses on investigating the functionality and mechanisms of LDH in stem cell fate regulation and tissue engineering through the design, optimization, and synthesis of LDH nanomaterials. In-depth studies of LDH, considering its significant variations in regulating stem cell functions and mechanisms under different culture environments, will provide new strategies for developing composite therapeutic systems for tissue regeneration and biomedical applications.

Topic title: 生物材料调控干细胞命运及神经类器官构建