Applications of Diels–Alder Chemistry in Biomaterials and Drug Delivery

Recent studies, leveraging click chemistry reactions, have significantly advanced the fields of biomaterials and drug delivery. Of these click reactions, the Diels–Alder cycloaddition is exceptionally valuable for synthetic organic chemistry and biomaterial design, as it occurs under mild reaction conditions and can undergo a retrograde reaction, under physiologically relevant conditions, to yield the initial reactants. In this review, potential applications of the Diels–Alder reaction are explored within the nexus of biomaterials and drug delivery. This includes an emphasis on key platforms such as polymers, nanoparticles, and hydrogels which utilize Diels–Alder for drug delivery, functionalized surfaces, bioconjugation, and other diverse applications. Specifically, this review will focus on the use of Diels–Alder biomaterials in applications of tissue engineering and cancer therapies, while providing a discussion of the advantages, platforms, and applications of Diels–Alder click chemistry.