Hydrophobically Modified Chitosan in Biomedical Applications: Great Expectations vs. Translational Reality.

Hydrophobically modified chitosan has attracted considerable interest as an amphiphilic biomaterial for drug delivery, antimicrobial systems, and tissue engineering. Despite extensive research and promising biological performance, only a limited number of these materials have advanced toward clinically relevant technologies. This Perspective argues that the major barriers to translation are no longer related to biological efficacy but to insufficient reproducibility, inconsistent structural characterization, and limited attention to process engineering and scalable manufacturing. Rather than providing another comprehensive review, we discuss hydrophobically modified chitosan from a translational perspective, following its development from chemical modification and self-assembly to formulation engineering and representative biomedical applications. We highlight how molecular design, processing conditions, and material characterization collectively determine the reliability and practical applicability of these systems. Finally, we outline key priorities for future research, including standardized characterization protocols, harmonized experimental methodologies, and the implementation of engineering-oriented development strategies. We propose that future progress will depend less on introducing new chemical modifications and more on integrating polymer chemistry with process engineering to improve reproducibility and facilitate clinical translation.