Enhanced activation of retinal progenitor cells by zinc silicate bioceramics for effective functional restoration in retinal degenerative diseases

Abstract Retinal degenerative diseases, primarily owing to the gradual loss of neuronal cells, could lead to blindness. Transplantation of retinal progenitor cells (RPCs), which had the unique ability to differentiate into neuronal cells, offered promising therapeutic potential for these diseases. However, a critical challenge in stem cell therapy was the efficient promotion of the directed proliferation and differentiation of progenitor cells. To overcome this limitation, we formulated a zinc silicate bioceramic (ZS) composite hydrogel. The experimental outcomes demonstrated that this novel material possessed substantial advantages and immense possibilities for mimicking the extracellular matrix environment, thereby effectively modulating stem cell proliferation and differentiation. Notably, it enhanced the differentiation of RPCs into neurons while suppressing glial cell differentiation. In particular, ZS had an exceptional capacity to induce the differentiation of RPCs into photoreceptor cells, a specialized type of neuronal cell. It was important to highlight that the ZS composite hydrogel predominantly facilitated the differentiation of RPCs through activation of the Tiam2‐Rac signaling pathway. Concurrently, it stimulated proliferation via activation of the AKT and ERK signaling pathways. The Zn ions in the ZS composite hydrogel primarily promoted the proliferation of RPCs, while the synergistic effect of Zn ions and Si ions contributed to reducing inflammatory factor expression and promoting the neuronal differentiation of RPCs. In conclusion, the meticulous modulation of RPC proliferation and differentiation mediated by ZS bioceramics held promise for novel therapeutic strategies of retinal degenerative diseases and neurodegenerative disorders.