Abstract
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.
Highlights
Bone defects or loss of bone, whether caused by trauma, congenital disorders or diseases, represent a significant burden for the population and the health system
Calcium phosphate nanoparticles have been successfully used for the delivery of a range of therapeutic factors for bone repair (Figure 1), some of which include antibiotics [9], anti-inflammatory agents and growth factors, such as bone morphogenetic factors (BMPs) and cytokines in order to enhance osteogenesis [10]
Neuhaus et al investigated the potential for a triple shell composed of calcium phosphate nanoparticles, siRNAs, and PEI (CaP/siRNA/CaP/PEI) for the delivery of siRNAs to knock down tumour necrosis factor alpha (TNF)-α for the treatment of tumour cells, and successfully reduced gene expression to 18% of the original value, while cell viability remained over 70% [106]
Summary
Bone defects or loss of bone, whether caused by trauma, congenital disorders or diseases, represent a significant burden for the population and the health system. In order to address this clinical challenge, there has been an increased interest in the development and administration of therapeutic factors to promote bone tissue regeneration These therapies are delivered systemically which has numerous disadvantages including the requirement for larger doses and the potential for off-target effects. Calcium phosphate nanoparticles have been successfully used for the delivery of a range of therapeutic factors for bone repair (Figure 1), some of which include antibiotics [9], anti-inflammatory agents and growth factors, such as bone morphogenetic factors (BMPs) and cytokines in order to enhance osteogenesis [10] They have shown promise for use in conjunction with gene therapy to deliver therapeutic cues for bone repNaainrompauterriaplso2s0e19s,,9,wx FhOeRrePEbEyR tRhEeVInEWanoparticles interact with the host tissue, producing3aofc2o2 mplex that can further enhance bone tissue repair and regeneration [10,11]
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