Mohammad Ebrahim Astaneh, Lalji Baldaniya, A. C. Singh, Ahmad Hussen, Alireza Hashemzadeh, Narges Fereydouni
Background and Aims: The escalation of chronic wounds necessitates advanced therapeutic strategies beyond current interventions. Hydrogel dressings, particularly injectable hydrogels, offer promising solutions due to their water absorption capacity, structural resilience, and ease of application. Combining exosomes with injectable hydrogels enhances wound healing through mechanisms such as re-epithelization and tissue regeneration. This review aims to explore the synergistic effects of exosome-loaded injectable hydrogels in creating a conducive microenvironment for wound healing, emphasizing their potential as a cell-free therapeutic approach for skin regeneration. Methods: This narrative review employed electronic databases and keyword search strategies to identify pertinent sources. Databases including Google Scholar, Scopus, Web of Science, and PubMed were utilized to retrieve relevant information. Selection criteria for sources were based on their alignment with the review's purpose, ensuring relevance and appropriateness for inclusion. Results: This investigation delineates various avenues for sourcing exosomes to be incorporated into injectable hydrogels, with particular emphasis on adipose-derived mesenchymal stem cells, macrophages, and polymorphonuclear neutrophils as primary sources. Moreover, it underscores that while existing research underscores the considerable potential of combining exosomes with injectable hydrogels in advancing skin regeneration, numerous hurdles persist in effectively characterizing, isolating, facilitating large-scale production for therapeutic applications, and ensuring the optimal storage conditions for exosomes. Simultaneously, challenges abound in augmenting the mechanical robustness of injectable hydrogels, accurately assessing cytotoxicity, establishing biocompatibility, enhancing adhesion properties, and ensuring controlled release mechanisms. Conclusion: Although exosome-loaded injectable hydrogels have shown significant effectiveness in treating various types of wounds, their synthesis and application pose significant challenges and limitations. Overcoming these hurdles comprehensively is crucial for researchers to improve the feasibility and efficacy of these advanced therapeutics. Doing so will maximize their potential in wound management practices.