Fibroblast-loaded carboxymethyl chitosan-aldehyde hyaluronic acid injectable hydrogel for scleral remodelling to prevent development of myopia.

High myopia severely threatens the visual health of adolescents, with pathological features of decreased collagen aggregation and scleral thinning, ultimately leading to axial elongation on preretinal imaging. Fibroblasts play crucial roles in scleral remodelling and myopia prevention. In this work, we developed a fibroblast-loaded carboxymethyl chitosan-aldehyde hyaluronic acid (CMCS-HA-CHO) injectable hydrogel for anti-scleral remodelling. The CMCS-HA-CHO hydrogel is formed through simple mixing under mild conditions via a Schiff base reaction between CMCS and HA-CHO. The CMCS-HA-CHO hydrogel can be injected into a posterior sclera with a low modulus, and the increasing modulus over time provides good mechanical support to the sclera. The hydrogel demonstrated excellent cytocompatibility and haemocompatibility, and the encapsulated fibroblasts maintained good activity. Both the hydrogel and fibroblast-loaded hydrogel effectively shortened the axial length of myopic eyes in guinea pigs in a deprivation model. In particular, the fibroblast-loaded hydrogel had the best therapeutic effect because of the synergy of cell therapy and mechanical support, which always shortened the eye axis within 4 weeks. Furthermore, increased collagen secretion promoted by fibroblasts can increase the thickness of the sclera and improve its biomechanical properties, ultimately repairing the physiological structure of the sclera. This fibroblast-loaded injectable hydrogel may represent a promising clinical approach for controlling myopia progression.