Reengineering Bone-Implant Interfaces for Improved Mechanotransduction and Clinical Outcomes.

The number of patients undergoing joint replacement surgery has progressively increased worldwide due to world population ageing. In the Unites States, for example, the prevalence of hip and knee replacements has increased more than 6 and 10 times, respectively, since 1980. Despite advances in orthopaedic implant research, including the development of novel implantable biomaterials, failures are still observed due to inadequate biomechanical compliance at the bone-implant interface. This comprises static and dynamic mechanical mismatch between the bone and the implant surface. The importance and robustness of biomechanical cues for controlling osteogenic differentiation of mesenchymal stem cells (MSC) have been highlighted in recent studies. However, in the context of bone regenerative medicine, it remains elusive how mechanobiological signals controlling MSC osteogenic differentiation dynamics are modulated in their interaction with the bone and with implants. In this review, we highlight recent technological advances aiming to improve host bone-implant interactions based on the osteogenic and mechanoresponsive potential of MSC, in the context of joint replacement surgery. First, we discuss the extracellular and intracellular mechanical forces underlying proper receptivity and stimulation of physiological MSC differentiation and linked osteogenic activity. Second, we provide a critical overview on how this knowledge can be integrated towards the development of biomaterials for improved bone-implant interfaces. Third, we discuss cross-disciplinarily which contributes to the next generation design of novel pro-active orthopaedic implants and their implantation success. Graphical Abstract.

Development of ß-TCP-Ti6Al4V structures: Driving cellular response by modulating physical and chemical properties.

Load-bearing implants success is strongly dependent on several physical and chemical properties that are known to drive cellular response. In this work, multi-material ß-TCP-Ti6Al4V cellular structures were designed to combine Ti6Al4V mechanical properties and ß-Tricalcium Phosphate bioactivity, in order to promote bone ingrowth as the bioactive material is being absorbed and replaced by newly formed bone. In this sense, the produced structures were characterized regarding roughness, wettability, ß-TCP quantity and quality inside the structures after fabrication and the pH measured during cell culture (as consequence of ß-TCP dissolution) and those aspects were correlated with cellular viability, distribution, morphology and proliferation. These structures displayed a hydrophilic behavior and results showed that the addition of ß-TCP to these cellular structures led to an alkalization of the medium, aspect that significantly influences the cellular response. Higher impregnation ratios were found more adequate for lowering the media pH and toxicity, and thus enhance cell adhesion and proliferation.