Tannic Acid as a Multifunctional Regulator in Calcium Phosphate Bone Biomaterials: Design Opportunities and Unresolved Challenges

Calcium phosphate cements and related inorganic bone biomaterials are clinically constrained by coupled limitations in mechanical integrity, degradation control, and susceptibility to infection, rather than by isolated material deficiencies. Although extensive efforts have been devoted to modifying these materials using polymers, fibres, ions, and bioactive agents, most strategies remain additive-centric, addressing individual performance metrics without accounting for cement-specific constraints that govern setting reactions, microstructural evolution, and long-term stability. Tannic acid is a naturally occurring polyphenol that has recently emerged across diverse biomaterial systems as a multifunctional chemical regulator capable of metal ion coordination, dynamic supramolecular bonding, and biological modulation. While its effects have been extensively investigated in hydrogels, coatings, and hybrid scaffolds, their relevance to calcium-rich, hydration-driven cementitious systems has not been critically resolved. This review addresses this disconnect by establishing a regulator-aware perspective for calcium phosphate-based biomaterials, using tannic acid as a model chemically active modifier. By synthesising evidence from polymeric systems alongside the limited but instructive body of work on calcium-containing and cementitious materials, this review distinguishes transferable from non-transferable mechanisms, elucidates how calcium ion competition, diffusion-limited transport, and crystallisation-controlled setting constrain multifunctional regulation, and identifies concentration-dependent trade-offs that are often overlooked. Rather than providing an exhaustive catalogue, tannic acid is positioned as a diagnostic regulator that exposes unresolved limitations in prevailing calcium phosphate cement modification paradigms. Through this framework, the review defines critical failure modes and delineates experimental priorities required for the rational evaluation and design of multifunctional regulators in next-generation calcium phosphate-based bone biomaterials.