Bioinspired polydopamine as a versatile platform for pharmaceutical and biomedical applications

Abstract

Polydopamine (PDA) can be exploited for multifunctional applications such as drug delivery, photothermal treatment, imaging, tissue engineering, gene delivery, and biointerface engineering. Due to its catechol/quinone chemistry, strong interfacial adhesion, metal-coordination capacity, redox activity and near-infrared (NIR)-responsiveness, it offers a unique basis for multifunctional integration in biomedical systems. Nonetheless, the largest hurdle for PDA is not to show multifunctionality anymore but to establish predictable structure-properties' biological relationships to achieve reproducible clinically relevant performance. PDA shows a high level of structural heterogeneity and physicochemical properties that depend on synthesis, while batch-to-batch variability, context-dependent degradation, formulation-dependent hemocompatibility, and limited standardized characterization continue to constrain translation. PDA-enabled clustered regularly interspaced short palindromic repeats (CRISPR) delivery, smart nanotheranostics, three-dimensional printed scaffolds, and other recent advances demonstrate the manufacturing capability of precision therapy and advanced biomaterials. Nonetheless, these new applications are still largely preclinical, and direct comparisons with established biomaterials, long-term safety data, scalable manufacturing strategies and regulatory evidence are lacking. This review includes the dependency of PDA structure and chemistry on interfacial behaviour, biological responses, and biomedical functionality. This review will also discuss advantages and limitations of PDA vs emerging derivatives and established biomaterials. Future advancement should pivot from function-driven material development towards the design of application-specific and quality-controlled PDAs. This shift should be facilitated by a standardized synthesis of assorted PDAs, a definition of their critical quality attributes, quantitative hemocompatibility and stability characterization, comparative benchmarking and clinically relevant validation. A shift of this nature is required for the transformation of PDA from a solution material to a predictable, reproducible, and clinically translatable material.