Abstract
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.
Highlights
Despite bone’s intrinsic ability to repair itself without scarring, 5–10% of all bone fractures result in delayed or non-union fractures [1], causing chronic pain for patients
This review provides a synopsis of the current state-of-the-art relating to the design of calcium phosphate nanoparticles as non-viral vectors and their application in ribonucleic acid (RNA)-based therapy for bone tissue regeneration
Another cationic polymer used for the surface functionalization of calcium phosphate to enhance cargo release is poly(lactic-co-glycolic acid) (PLGA), which is composed of lactic acid and glycolic acid connected by ester bonding [175]
Summary
Despite bone’s intrinsic ability to repair itself without scarring, 5–10% of all bone fractures result in delayed or non-union fractures [1], causing chronic pain for patients. Autologous bone grafts, the “gold standard” currently employed to treat delayed or non-union fractures, exhibit a high incidence of failure and numerous limitations, including donor site morbidity, lack of tissue availability, and invasive surgery [3] Similar drawbacks, such as unfavorable immune responses, rejection rates and lack of graft availability, are found in the use of allografts and xenografts, whereas synthetic bone graft substitutes often lack biocompatibility and osteogenic potential [4]. Calcium phosphate nanoparticles hold particular potential in this regard for bone-related conditions as they have a strong affinity for binding to nucleic acids [10,11] They are well-accepted by the body and have a significant surface-to-volume ratio that allows for a higher driving force for diffusion, increased particle solubility and adhesion to specific proteins [12]. The potential for surface functionalization methods to improve the stability, transfection and safety of calcium phosphate will be discussed
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