Hydrogel–exosome synergistic system: mechanisms, applications and future prospects in regenerative medicine

Hydrogels and exosomes are complementary and thus can be combined for regenerative medicine and emerging therapies. This strategy leverages the advantages of hydrogels to enhance the therapeutic potential of exosomes. Hydrogels offer numerous therapeutic and regenerative advantages, such as tailorable mechanical properties, a supportive extracellular matrix-like microenvironment, superior biocompatibility, rapid responses to environmental stimuli, and the ability to encapsulate and control the release of therapeutic agents. These attributes can be utilized to enable the long-acting delivery of exosomes. Exosomes, small extracellular vesicles (30-150 nm) secreted by cells, carry bioactive molecules such as proteins, lipids, and nucleic acids, mediating intercellular communication and modulating cellular behaviors. The integration of hydrogels and exosomes represents a potential approach in regenerative medicine, leveraging their synergistic properties to enhance tissue repair and regeneration. This combination has been reported to enhance wound healing, promote cartilage repair, and ameliorate neuronal injury. Recent advancements include the development of smart hydrogels that respond to environmental stimuli (e.g., pH, temperature) to control exosome release, optimizing the therapeutic efficacy. Additionally, exosome engineering for enhanced cargo loading and targeting capabilities further advances precision regenerative medicine. This review explores the latest progress, challenges, and future directions in harnessing hydrogels and exosomes for recently developed regenerative medicine and therapeutic applications.