scholarly journals Calcium Phosphate Nanoparticles-Based Systems for RNAi Delivery: Applications in Bone Tissue Regeneration

Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 146 ◽  
Author(s):  
Tanya J. Levingstone ◽  
Simona Herbaj ◽  
John Redmond ◽  
Helen O. McCarthy ◽  
Nicholas J. Dunne
Keyword(s):  
Gene Therapy ◽  
Calcium Phosphate ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Viral Vectors ◽  
Bone Repair ◽  
Transfection Efficiency ◽  
Bone Tissue Regeneration ◽  
Calcium Phosphate Nanoparticles

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.

scholarly journals Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

2020 ◽  
Author(s):  
Miaomiao He ◽  
Ce zhu ◽  
Huan Xu ◽  
dan Sun ◽  
Chen Chen ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Repair ◽  
Graphene Nanosheets ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

scholarly journals Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1570 ◽  
Author(s):  
Tanya J. Levingstone ◽  
Simona Herbaj ◽  
Nicholas J. Dunne
Keyword(s):  
Tissue Engineering ◽  
Calcium Phosphate ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Viral Vectors ◽  
Bone Repair ◽  
Calcium Phosphates ◽  
The Body ◽  
Therapeutic Factors ◽  
Calcium Phosphate Nanoparticles

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.

scholarly journals Bone Tissue Regeneration by Collagen Scaffolds with Different Calcium Phosphate Coatings: Amorphous Calcium Phosphate and Low-Crystalline Apatite

Materials ◽  
2021 ◽  
Vol 14 (19) ◽  
pp. 5860
Author(s):  
Syama Santhakumar ◽  
Ayako Oyane ◽  
Maki Nakamura ◽  
Yuto Yoshino ◽  
Mohammed Katib Alruwaili ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Calcium Phosphate ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Amorphous Calcium Phosphate ◽  
Bone Tissue Regeneration ◽  
Apatite Coating ◽  
Low Crystalline ◽  
Mineralized Collagen

Surface-mineralized collagen sponges have attracted much attention as scaffolds for bone tissue engineering. Recently, we developed amorphous calcium phosphate (ACP) and low-crystalline apatite coating processes on collagen sponges. In the present study, we applied these coating processes to granular collagen sponges (referred to as Col) to compare the bone tissue regeneration capabilities of ACP-coated and apatite-coated Col (referred to as Col-ACP and Col-Ap, respectively) using a rat cranial bone defect model. According to micro-CT and histological analyses, Col-Ap enhanced bone tissue regeneration compared to Col, whereas Col-ACP did not. These results not only demonstrated the superior bone tissue regeneration capability of Col-Ap, but also indicated limitations of the in vitro simulated body fluid (SBF) test used in our previous study. Despite the apatite-forming ability of Col-ACP in SBF, it was ineffective in improving bone tissue regeneration in vivo, unlike Col-Ap, most likely due to the quick resorption of the ACP coating in the defect site. The present results clarified the importance of the coating stability in vivo and revealed that the low-crystalline apatite coating was more beneficial than the ACP coating in the fabrication of surface-mineralized collagen sponges for use as bone tissue engineering scaffolds.

scholarly journals Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

2020 ◽  
Author(s):  
Miaomiao He ◽  
Ce zhu ◽  
Huan Xu ◽  
dan Sun ◽  
Chen Chen ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Repair ◽  
Graphene Nanosheets ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

scholarly journals Icaritin Enhancing Bone Formation Initiated by Sub-Microstructured Calcium Phosphate Ceramic for Critical Size Defect Repair

2020 ◽  
Vol 7 ◽  
Author(s):  
Haitao Peng ◽  
Jianxiao Li ◽  
Yanan Xu ◽  
Guoyu Lv
Keyword(s):  
Calcium Phosphate ◽  
Bone Formation ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Calcium Phosphate Ceramic ◽  
Dose Dependent

Adequate bone tissue regeneration has been challenging to achieve at critical-sized bone defects caused by disease. Bone tissue engineering using a combination of scaffolds and bioactive factors provides new hope for the treatment of this extreme condition. Icaritin, a herb-derived chemical, has shown its ability to enhance bone formation both in vitro and in vivo, and it has been found that sub-micron surface structure instructs bone formation in calcium phosphate ceramics (CaPs). Here, we evaluated the possibility of using a submicron surface structured CaP ceramic as the carrier of icaritin for bone tissue regeneration in critical-sized bone defects. Icaritin, an herb-derived chemical, was loaded into a submicron surface structured porous calcium phosphate ceramic (Ø12.8 × 3 mm) to get samples with 0, 10, 50, 250, and 1,250 µg icaritin per CaP disc (M0, M10, M50, M250, M1250 groups, respectively). In vitro evaluation with the certain dosages correlated to those released from the samples showed a dose-dependent enhancement of osteogenic differentiation and mineralization of human bone marrow stromal cells with the presence of osteogenic factors in the culture medium, indicating icaritin is an osteopromotive factor. After intramuscular implantation of the samples in dogs for 8 weeks, a dose-dependent of bone formation was seen with enhanced bone formation at the dosage of 50 and 250 µg. To evaluate the in vivo osteogenic potentials of icaritin-containing CaP ceramic scaffolds in the orthopedic site, a 12.8 mm calvarial defect model in rabbits was established. Micro-computed tomography (micro-CT) and histology results at weeks 4, 8 and 12 post-surgery showed more newly formed bone in M250 group, with correspondingly more new vessel ingrowth. The results presented herein suggested that being osteopromotive, icaritin could enhance bone formation initiated by sub-microstructured CaP ceramics and the CaP ceramics scaffold incorporating icaritin is a promising biomaterial for the treatment of critical-sized defect.

scholarly journals Chitosan Scaffolds Containing Calcium Phosphate Salts and rhBMP-2: In Vitro and In Vivo Testing for Bone Tissue Regeneration

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e87149 ◽  
Author(s):  
Rodrigo Guzmán ◽  
Stefania Nardecchia ◽  
María C. Gutiérrez ◽  
María Luisa Ferrer ◽  
Viviana Ramos ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Tissue Regeneration ◽  
In Vivo Testing ◽  
Chitosan Scaffolds ◽  
Phosphate Salts

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

scholarly journals Nanoscale Strontium-Substituted Hydroxyapatite Pastes and Gels for Bone Tissue Regeneration

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1611
Author(s):  
Caroline J. Harrison ◽  
Paul V. Hatton ◽  
Piergiorgio Gentile ◽  
Cheryl A. Miller
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Culture Media ◽  
Full Range ◽  
Sol Gel ◽  
Tissue Growth ◽  
Bone Tissue Regeneration ◽  
Tissue Culture Media ◽  
Bone Deposition

Injectable nanoscale hydroxyapatite (nHA) systems are highly promising biomaterials to address clinical needs in bone tissue regeneration, due to their excellent biocompatibility, bioinspired nature, and ability to be delivered in a minimally invasive manner. Bulk strontium-substituted hydroxyapatite (SrHA) is reported to encourage bone tissue growth by stimulating bone deposition and reducing bone resorption, but there are no detailed reports describing the preparation of a systematic substitution up to 100% at the nanoscale. The aim of this work was therefore to fabricate systematic series (0–100 atomic% Sr) of SrHA pastes and gels using two different rapid-mixing methodological approaches, wet precipitation and sol-gel. The full range of nanoscale SrHA materials were successfully prepared using both methods, with a measured substitution very close to the calculated amounts. As anticipated, the SrHA samples showed increased radiopacity, a beneficial property to aid in vivo or clinical monitoring of the material in situ over time. For indirect methods, the greatest cell viabilities were observed for the 100% substituted SrHA paste and gel, while direct viability results were most likely influenced by material disaggregation in the tissue culture media. It was concluded that nanoscale SrHAs were superior biomaterials for applications in bone surgery, due to increased radiopacity and improved biocompatibility.

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