Advanced biomaterials in tissue engineering: A critical review of nanocomposites based on bacterial cellulose, MXenes, hydroxyapatite, and metal particles for regenerative medicine.

Soft and hard tissues have limited regenerative potential that fuels the search for advanced biomaterials able to mimic their complex dynamics better. Individually, bacterial cellulose (BC) provides excellent biocompatibility but lacks inherent bioactivity and functional properties needed to promote tissue regeneration. Hydroxyapatite (HAp) offers osteoconductivity but shows brittleness. Metal nanoparticles (MNPs) have antioxidant, antimicrobial, and drug-delivery properties, but may be toxic. Lastly, MXenes possess good conductivity but lack knowledge of their long-term biocompatibility. To address these material limitations, approaches like genetic modifications to BC synthesis and surface modifications of MXenes and MNPs are explored. This review examines synthesis methods, structural properties, and biomedical applications of individual and hybrid materials based on BC, MXene, HAp, and MNPs. Analysis of existing composite materials establishes a strong recognition of their compatibility, which supports the possibility of their successful integration into a multifunctional BC/MXene/MNP/HAp four-component composite. It is expected to exhibit a combination of osteoinduction, electrical conductivity, antibacterial activity, and structural support to improve tissue repair. However, challenges include the potential cytotoxicity of MNPs and limited studies on the broader impact of MXenes on gene expression beyond specific markers. This review sheds light on the development of a new composite material that can address current limitations in biomaterial functionality by summarizing current knowledge and highlighting critical gaps. It aims to establish a foundation and inspire future studies towards rationally designing BC/MXene/MNP/HAp composites for advanced regenerative therapies.