Engineering biomaterials to improve cytokine therapies for wound healing

Recombinant cytokines have been used as therapeutics for cancers, autoimmune diseases, and infectious diseases, but their application in wound healing and tissue regeneration remains relatively underdeveloped. Short half-lives, narrow therapeutic windows, and a myriad of adverse effects due to pleiotropy and redundancy have limited their clinical use. Biomaterial-based delivery platforms such as hydrogels, particles, and scaffolds have gained traction as engineering strategies to bridge this translational gap. Despite their popularity in preclinical research, the last FDA approved biomaterial-based cytokine therapeutic, becaplermin, was approved in 1997. Unlike reviews that focus on material design alone, we investigate clinical trials from 2012 to present day and look at the barriers and bottlenecks of translating this technology beyond the bench. This review focuses on release kinetics, design parameters, and practical applications of cytokine-loaded hydrogels, particles, and scaffolds to accelerate wound healing and regenerate functional tissue after soft tissue damage. We offer insights about future directions for preclinical testing and further engineering considerations to aid in their translation to clinical care for patients with soft tissue injuries.