Amorphous polyphosphate, a smart bioinspired nano-/bio-material for bone and cartilage regeneration: towards a new paradigm in tissue engineering.

Recent developments in the field of biomaterials for tissue engineering open up new opportunities for regenerative therapy and prevention of progression of osteo-articular damage/impairment. A key advancement was the discovery of the regenerative activity of a group of physiologically occurring high-energy polymers, inorganic polyphosphates (polyP). These bio-polymers, in suitable bioinspired formulations, turned out to be capable of inducing proliferation and differentiation of mesenchymal stem cells into osteogenic or chondrogenic lineages through differential gene expression (morphogenetic activity). Unprecedented is the property of these biopolymers to deliver high-energy phosphate in the extracellular space to promote anabolic processes including extracellular matrix synthesis in bradytrophic tissues such as cartilage and mineralized bone. This review summarizes the biological effects of these unique bio-polymers, not yet met by other biomaterials and depending on their specific formulation as smart amorphous nanoparticles/microparticles with different counterions. In addition, polyP in combination with other, hydrogel-forming polymers provides the basis for the fabrication of hardenable bio-inks applicable in additive manufacturing/3D printing and 3D cell bioprinting of regeneratively active patient-specific osteo-articular implants. The future prospects of this innovative technology are discussed.