Biological Responses to Biomaterials: Mechanisms and Opportunities for Enhanced Oral Tissue Regeneration.

Recent advances in biomaterials for dental applications have shown great promise in the reconstruction and regeneration of oral tissue, including soft connective tissue (mucosa and gingiva), bone and periodontal structures. Achieving successful oral tissue regeneration requires not only providing support for complex structures but also leveraging the host immune response to promote healing while minimising adverse reactions. The important biological reactions to biomaterials in oral tissue regeneration are examined in this review, with an emphasis on how immune modulation, specifically, the functions of macrophages and T cells, determine the outcome of tissue repair. Key biomaterial properties, including bioactivity, biocompatibility and tissue integration, are discussed, as well as the influence of immune responses such as the foreign body reaction (FBR) and inflammation. Additionally, we highlight advanced strategies for designing immunomodulatory biomaterials, including surface modifications and coatings, controlled release systems incorporating immunomodulatory ions and molecules and emerging cell-free therapies, including the applications of autologous blood products and extracellular vesicles. These strategies aim to overcome challenges such as chronic inflammation, immune rejection and poor tissue integration, demonstrating the potential of immunomodulatory biomaterials to enhance the effectiveness and durability of regenerative therapies for oral tissues.