Injectable hydrogels incorporating cell-derived nanocarriers for tumor therapy and regenerative medicine

Cancer therapy and regenerative medicine still face significant clinical challenges, urgently requiring advanced strategies capable of precisely delivering therapeutic drugs and effectively modulating the pathological microenvironment. Cell-derived nanocarriers demonstrate potential in drug delivery due to their inherent biocompatibility, low immunogenicity, and specific targeting capabilities. However, in vivo applications of free cell-derived nanocarriers are often limited by rapid clearance from the bloodstream, short retention times at target sites, and susceptibility to inactivation of bioactive components. To overcome these limitations, incorporating cell-derived nanocarriers in injectable hydrogels to construct composite platform has shown remarkable potential in biomaterials fields. This review provides a comprehensive overview of the integration of hydrogel networks with diverse bioactive nanocarriers. Specifically, we compare the unique features of various nanocarriers and the advantages and limitations of different hydrogel crosslinking strategies. Furthermore, we highlight the key roles of the hydrogel platforms, such as preserving the bioactivity of nanocarriers, elevating local concentrations of nanocarriers, and enabling controlled payload release in situ. The construction strategies for the nanocarrier-incorporated hydrogel systems are discussed, ranging from physical encapsulation to dynamic chemical bond anchoring of the nanocarriers. Subsequently, the applications in tumor therapy and regenerative medicine are emphasized. Finally, the challenges and future directions in standardized production, precise release regulation, and clinical translation of the composite hydrogel systems are discussed in detail.