Assessing the effects of strontium releasing titanium implants on the behaviour of human umbilical vein endothelial cells

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Abstract

Introduction: Aseptic loosening of an orthopaedic implant due to the unsatisfactory attachment to the bone remains one of the most common reasons for failure of these implants. One of the possible approaches for improving the connection between the implanted biomaterial and the bone tissue being formed is the incorporation of bioactive agents onto the surface of the biomaterial to promote bone and blood vessel formation. This work investigated the effects of strontium (Sr), a known osteogenic and angiogenic agent, incorporated in surfaces of 3D printed titanium implants on the behaviour of human umbilical vein endothelial cells (HUVECs), to determine its potential role in improving osseointegration by promoting an early development of a well vascularized bone. Methods: 3D printed titanium implants were subjected to plasma electrolytic oxidation (PEO) in electrolytes with and without Sr addition. The effects of Sr incorporated on the surfaces were subsequently tested in vitro by assessing the morphology, proliferation, wound healing ability and angiogenic potential of HUVECs. In addition, a coculture model with conditioned medium from mesenchymal stromal cells (MSCs) was included for investigations of the angiogenic potential. Results: The characterization of the PEO-treated titanium implants confirmed comparable topography and distinct chemical composition of samples treated in electrolytes without (PT) and with Sr (PT-Sr). Despite the good initial attachment, HUVECs showed a tendency to gradually leave both PT and PT-Sr implants. No improvement in proliferation of HUVECs seeded on PT-Sr implants was observed, yielding comparable results with the PT implants. The ions released from the PT and PT-Sr surfaces did not instigate faster wound healing ability of HUVECs and the direct contact of cells with the surfaces did not elicit paracrine signalling which would contribute to faster closure of the wound. The coculture model revealed higher angiogenic potential of HUVECs seeded on the PT and PT-Sr surfaces when cultured in the presence of conditioned media obtained from MSCs, implying the importance of interactions among these cell types for achieving successful bone repair. Discussion and conclusions: Comparison of the obtained data and evidence found in the literature implied that the 3D printed and PEO-treated implants could not support thriving of endothelial cells, most probably due to the topography and associated roughness of the surfaces given by the method employed for the 3D printing of these implants. However, with consideration to the physical and chemical complexity of the implants, further tests will have to be conducted to validate these assumptions.