Type I Collagen-Apatite Fibrillar Nanocomposites: Mineralization, Crosslinking and Anti-Inflammatory Cocrystal Impregnation for Bone Tissue Engineering

Self-assembly and mineralization of type I collagen (Col) with nanocrystalline apatite (nAp), by adding a solution of Ca(OH)2 to a stirred Col-H3PO4 solution by fast dripping, allowed the preparation of Col/nAp fibrils with good crystallographic control of the mineral phase. In this work, in addition, we have cross-linked the mineralized fibers by using different reagents, namely glutaraldehyde (GTA), tannic acid (TA), 1-Ethyl-3-(3-dimethyl aminopropyl)-carbodiimide combined with N-Hydroxysuccinimide (EDC/NHS), and genipin (GP), aimed at producing different types of biopolymeric Col/nAp-based drug delivery scaffolds. In parallel, we have investigated two different methods to impregnate the scaffolds with molecules of the cocrystal diclofenac-metformin (DF-MET). The result, when using TA as a crosslinking reagent, shows the sequence of mineralized fibrils impregnation followed by crosslinking leads to maximum cocrystal molecule loading. The impregnated material is expected to be useful in settings with excessive and prolonged inflammation, since they affect negatively the fracture healing/bone repair processes, especially during the early stages of healing.