Smart and injectable hydrogels for cancer treatment and other biomedical applications

The tumor microenvironment (TME) has specific features distinct from normal tissues, making these stimuli suitable for responsive and localized therapy. Injectable hydrogels have been identified as promising site-specific drug delivery carriers due to their ability to conform to irregular anatomical spaces and form in situ depots. Smart hydrogels, in particular, are engineered to respond to TME-relevant stimuli to facilitate controlled and sustained release of therapeutic agents locally within the tumor environment. This review provides an overview of injectable smart hydrogels based on cross-linking methods and how they influence injectability, self-healing, and responsiveness. It also discusses new designs of dual- and multi-responsive hydrogels that can respond to the multifactorial nature of the TME. Incorporating nanomaterials into hydrogel matrices is also covered, offering enhanced functionality for various biomedical applications. While the primary interest is cancer therapy, the design principles and methodologies introduced here are equally relevant to other biomedical applications such as wound healing, regenerative medicine, and inflammation-targeted therapy.