Bone injuries and diseases constitute a burden both socially and economically, as the consequences of a lack of effective treatments affect both the patients’ quality of life and the costs on the health systems. This impended need has led the research community’s efforts to establish efficacious bone tissue engineering solutions. There has been a recent focus on the use of biomaterial-based nanoparticles for the delivery of therapeutic factors. Among the biomaterials being considered to date, calcium phosphates have emerged as one of the most promising materials for bone repair applications due to their osteoconductivity, osteoinductivity and their ability to be resorbed in the body. Calcium phosphate nanoparticles have received particular attention as non-viral vectors for gene therapy, as factors such as plasmid DNAs, microRNAs (miRNA) and silencing RNA (siRNAs) can be easily incorporated on their surface. Calcium phosphate nanoparticles loaded with therapeutic factors have also been delivered to the site of bone injury using scaffolds and hydrogels. This review provides an extensive overview of the current state-of-the-art relating to the design and synthesis of calcium phosphate nanoparticles as carriers for therapeutic factors, the mechanisms of therapeutic factors’ loading and release, and their application in bone tissue engineering.
Bone-related injury and disease constitute a significant global burden both socially and economically. Current treatments have many limitations and thus the development of new approaches for bone-related conditions is imperative. Gene therapy is an emerging approach for effective bone repair and regeneration, with notable interest in the use of RNA interference (RNAi) systems to regulate gene expression in the bone microenvironment. Calcium phosphate nanoparticles represent promising materials for use as non-viral vectors for gene therapy in bone tissue engineering applications due to their many favorable properties, including biocompatibility, osteoinductivity, osteoconductivity, and strong affinity for binding to nucleic acids. However, low transfection rates present a significant barrier to their clinical use. This article reviews the benefits of calcium phosphate nanoparticles for RNAi delivery and highlights the role of surface functionalization in increasing calcium phosphate nanoparticles stability, improving cellular uptake and increasing transfection efficiency. Currently, the underlying mechanistic principles relating to these systems and their interplay during in vivo bone formation is not wholly understood. Furthermore, the optimal microRNA targets for particular bone tissue regeneration applications are still unclear. Therefore, further research is required in order to achieve the optimal calcium phosphate nanoparticles-based systems for RNAi delivery for bone tissue regeneration.
Thin-walled tubes loaded in bending are prone to failure by buckling. It is difficult to predict the loading conditions which cause buckling, especially for tubes of non-standard cross section. Insights into buckling prevention might be gained by studying this phenomenon in the exoskeletons of insects and other arthropods. We investigated the leg segments (tibiae) of five different insects: the locust (Schistocerca gergaria), american cockroach (Periplaneta americana), death's head cockroach (Blaberus discoidalis), stick insect (Parapachymorpha zomproi) and bumblebee (Bombus terrestris audax). These were tested to failure in cantilever bending and modelled using finite element analysis (FEA). The tibiae of the locust and the cockroaches were found to be approximately circular in shape. Their buckling loads were well predicted by linear elastic FEA, and also by one of the analytical solutions available in the literature for elastic buckling. The legs of the stick insect are also circular in cross section but have several prominent longitudinal ridges. We hypothesised that these ridges might protect the legs against buckling but we found that this was not the case: the loads necessary for elastic buckling were not reached in practice because yield occurred in the material, causing plastic buckling. The legs of bees have a non-circular cross section due to a pollen-carrying feature (the corbicula). We found that this did not significantly affect their resistance to buckling.
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