Role of Pyridoxal 5'-Phosphate at the Titanium Implant Interface In Vivo: Increased Hemophilicity, Inactive Platelet Adhesion, and Osteointegration.

Abstract

Titanium is the most biocompatible inorganic biomaterial with a long history of use in orthopedic and dental implants. However, promoting rapid and effective bone formation and integration onto etched, rough TiO₂ surfaces has been a challenging topic. Here, 21 commercially available molecules are examined that met the following criteria: (1) contain phosphonic acid for stable immobilization onto TiO₂ surfaces and (2) have a molecular weight less than 500 Da for negligible coating thickness. Of these molecules, the surface immobilization of pyridoxal 5'-phosphate (PLP), an active form of vitamin B₆ , dramatically increases the hemophilic property of the surface and accelerated osteointegration in vivo. Analysis shows that PLP promotes surface binding of serum albumin and other plasma proteins by Schiff-base formations via its aldehyde group, providing a platform suitable for osteoblast adhesion. PLP also retards blood coagulation more than the widely used citric acid at the TiO₂ surface. As PLP is capable of maintaining an inactivated status of surface-adsorbed platelets, delayed coagulation at the implant-blood interface allows for sufficient supply of growth factors from blood plasma and migration of osteoblasts. The results suggest that PLP can be widely applicable as a biocompatible, effective coating compound to promote osteointegration of titanium-based implants.