Osteoporosis and degenerative endocrine diseases are some of the major causes of disability in the elderly. The feedback loop in the endocrine system works to control the release of hormones and maintain the homeostasis of metabolism, thereby regulating the function of target organs. The breakdown of this feedback loop results in various endocrine and metabolic disorders, such as osteoporosis, type II diabetes, hyperlipidemia, etc. The direct regulation of redox homeostasis is one of the most attractive strategies to redress the imbalance of the feedback loop. The biophysical regulation of redox homeostasis can be achieved through engineered dynamic hydrogel niches, with which cellular mechanics and redox homeostasis are intrinsically connected. Mechanotransduction-dependent redox signaling is initiated by cell surface protein assemblies, cadherins for cell-cell junctions, and integrins for cell-ECM interactions. In this review, we focused on the biophysical regulation of redox homeostasis via the tunable cell-ECM interactions in the engineered dynamic hydrogel niches. We elucidate processes from the rational design of the hydrogel matrix to the mechano-signaling initiation and then to the redox response of the encapsulated cells. We also gave a comprehensive summary of the current biomedical applications of this strategy in several degenerative endocrine disease models.
Keywords: degenerative endocrine disease; engineered hydrogel niches; osteoporosis; redox homeostasis.