The bioactive trinity: Integrating chitosan, cellulose nanofibrils, and mesoporous bioactive glass nanoparticles for multifunctional periodontal tissue engineering.

Periodontitis is a chronic inflammatory disease that leads to the progressive destruction of the periodontal ligament, cementum, and alveolar bone. This disease poses a global public health challenge due to its impacts on systemic health and the substantial economic burden it imposes. Effective periodontal regeneration requires the coordinated restoration of multiple tissues under complex conditions, necessitating multifunctional biomaterials capable of providing mechanical stability, microbial barrier function, osteoconductivity, and angiogenic potential. To address the multifactorial challenges of periodontal regeneration, this review highlights recent studies pointing to the integration of natural polymers, such as chitosan (CS) and cellulose nanofibrils (CNFs), with mesoporous bioactive glass nanoparticles (MBGNs) within a unified framework. These components are discussed within the concept of the "bioactive trinity," wherein their complementary properties enable the development of multifunctional systems that are more efficient than conventional materials used in isolation. CS offers antimicrobial protection and compatibility with soft tissues, such as gingiva. CNFs function as structural reinforcements, compensating for the mechanical brittleness of CS while supporting structural organization and cellular orientation within the periodontal ligament. MBGNs, on the other hand, act as bioactive signaling agents, enabling the controlled release of therapeutic ions (Ca2+, Si4+, Zn2+, Sr2+) that regulate osteogenesis, thereby promoting the formation of mineralized tissue in the alveolar bone. The integration of these three components establishes a promising multifunctional platform in which structural integrity, biological activity, and biochemical signaling are intrinsically coupled. The translational potential, as well as the remaining challenges regarding integrated multi-tissue regeneration and comprehensive biosafety assessments-are discussed. Nevertheless, the bioactive trinity emerges as a significant trend in the development of advanced biomaterials, with the potential to guide future strategies in periodontal regeneration.