Bioactive glasses and polyphenols: towards synergistic biological effects for tissue regeneration

Since the discovery of bioactive glasses (BAGs), extensive research has been performed to refine their biological properties and enhance their regenerative potential. Progress in this field has not only focused on tailoring BAGs compositions and creating new synthesis methods but also addressed their association with other therapeutic agents. These associative strategies aim to provide multifunctional biomaterials and elicit synergistic/complementary biological effects that accelerate tissue repair and address a wide range of complex regenerative microenvironments (infection, oxidative stress, etc.). Among these approaches, the combination of ion-doped BAGs with natural polyphenols (PPhs) has shown significant potential in bone regeneration, wound healing, and cancer treatment. This review provides a comprehensive analysis of the BAGs-PPhs hybrid systems, detailing the various methods used for their association and the underlying mechanisms and factors governing BAGs and PPhs interactions. In addition, particular attention is given to how these interactions affect the release and prolong the bioavailability and reactivity of natural PPhs. This review discusses the effect of BAGs-PPhs coupling on BAGs' apatite forming ability and PPhs' antioxidant properties, and highlights key in vitro cellular findings on the osteogenic, angiogenic, immunomodulatory and cancer suppressive properties of BAGs-PPhs constructs, which are supported with in vivo evidence on therapeutic potential of these biomaterials. By offering an overview of the current advancements in this field, this review not only underscores the biomedical relevance of BAGs and PPhs coupling but also outlines existing challenges and identifies research perspectives for accelerating the translation of these biomaterials into clinical applications.