Development of a modified calcium-based composite ceramic bone graft material

Composites consisting of both calcium aluminum oxide and hydroxyapatite were tested for their applicability as bone replacement scaffolds. Implanted bone scaffolds may fail due to a variety of reasons, including mechanical and biological failure. Mechanical failure may occur as a result of dissimilar properties between the surrounding healthy bone and the scaffold. Biological failure can occur due to integration problems at the interface of the scaffold and the natural bone, or as a result of implant associated infections as a result of bacterial attachment and biofilm formation. Calcium aluminum oxide:hydroxyapatite composites were developed that address these three modes of implant failure through physical modification of the composition of the materials and chemical modification of the interface of the material.;The composites were evaluated for phase composition, elastic modulus, modulus of rupture, degradability, osteoblast attachment, percent viability and proliferation. Characterization was completed using powder x-ray diffraction (PXRD), a four point bending test, scanning electron microscopy (SEM), scanning electron microscopy-energy dispersive x-ray spectroscopy (SEM-EDS), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, fluorescence spectroscopy, direct infusion quadrupole-time of flight mass spectrometry (Q-TOF MS), Escherichia coli N-phenylnaphthylamine (NPN) uptake and bacterial turbidity tests, and Live/DeadRTM and alamarBlueRTM tissue culture assays. Composites with greater than 10% HA by mass were mechanically weak and ruled out as scaffolds. However, 1-5% HA composites were mechanically similar to non-load bearing bone and all resulted in increased osteoblast response at extended time points. The antimicrobial peptide Inverso-CysHHC10 was successfully linked to the 5% HA composite using an interfacial alkene-thiol click reaction. The linked AMP retained its effectiveness against Escherichia coli based on NPN uptake assays and bacterial turbidity tests. Most importantly, the immobilization of the antimicrobial peptide did not affect the increased osteoblast response observed on the unmodified 5% HA. The Inverso-CysHHC10 modified composites present a new class of composite biomaterials that are able to simultaneously address issues with mechanical mismatching, osteoconductivity and implant site infection.