Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

Cheng, Tegan L.; Murphy, Ciara M.; Ravarian, Roya; Dehghani, Fariba; Little, David

doi:10.1177/2041731415609448

Cited by 19 publications

(14 citation statements)

References 44 publications

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“…Sucrose acetate isobutyrate (SAIB) is a sugar‐based polymer that is highly viscous and hydrophobic. It has been used as a drug delivery carrier for BMPs, with addition of small amounts of ethanol as a solvent to reduce the viscosity and make it injectable . In preclinical orthopedic models, this has been used to prevent femoral head collapse in a porcine model of hip osteonecrosis, as well as to promote open fracture healing in a rat model .…”

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“…Zoledronic acid (ZA), is a potent bone anti‐resorptive that can lead to additional net bone formation in an orthopedic setting . The use of ZA and hydroxyapatite (HA) microparticles have been previously shown to enhance SAIB/BMP‐2‐induced bone formation . Model systems have included: an ex vivo analysis of PDIB coating of bone allografts; a rat muscle pouch study where freeze‐dried bone allografts with different coating combinations was implanted in the quadriceps; and a rat critical defect model, stabilized by an internal polyacetyl plate and with the bone allografts press‐fit within the gap.…”

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“…It has been used as a drug delivery carrier for BMPs, with addition of small amounts of ethanol as a solvent to reduce the viscosity and make it injectable. 10,11 In preclinical orthopedic models, this has been used to prevent femoral head collapse in a porcine model of hip osteonecrosis, 12 as well as to promote open fracture healing in a rat model. 13 Historically, SAIB was also used as part of a more complex polymer coating system for BMP delivery in a vicryl mesh implant model.…”

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A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

Cheng

Leblanc

Kalinina

et al. 2019

Journal Orthopaedic Research

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Bone allografts are inferior to autografts for the repair of critical‐sized defects. Prior studies have suggested that bone morphogenetic protein‐2 (BMP‐2) can be combined with allografts to produce superior healing. We created a bioactive coating on bone allografts using polycondensed deoxyribose isobutyrate ester (PDIB) polymer to deliver BMP‐2 ± the bisphosphonate zoledronic acid (ZA) and tested its ability to enhance the functional utility of allografts in preclinical Wistar rat models. One ex vivo and two in vivo proof‐of‐concept studies were performed. First, PDIB was shown to be able to coat bone grafts (BGs). Second, PDIB was used to coat structural allogenic corticocancellous BG with BMP‐2 ± ZA ± hydroxyapatite (HA) microparticles and compared with PDIB‐coated grafts in a rat muscle pouch model. Next, a rat critical defect model was performed with treatment groups including (i) empty defect, (ii) BG, (iii) collagen sponge + BMP‐2, (iv) BG + PDIB/BMP‐2, and (v) BG + PDIB/BMP‐2/ZA. Key outcome measures included detection of fluorescent bone labels, microcomputed tomography (CT) quantification of bone, and radiographic healing. In the muscle pouch study, BMP‐2 did not increase net bone volume measured by microCT, however, fluorescent labeling showed large amounts of new bone. Addition of ZA increased BV by sevenfold (p < 0.01). In the critical defect model, allografts were insufficient to promote reliable union, however, union was achieved in collagen/BMP‐2 and all BG/BMP‐2 groups. Statement of clinical significance: These data support the concept that PDIB is a viable delivery method for BMP‐2 and ZA delivery to enhance the bone forming potential of allografts. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2278–2286, 2019

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A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

Cheng

Leblanc

Kalinina

et al. 2019

Journal Orthopaedic Research

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“…Various tetracyclines and bisphosphonates have been frequently used as bone-targeting moieties in nanotechnology-based therapy, but limitations related to these drugs remain. 15,16 Tetracycline binds mainly with less-crystalline hydroxyapatites (newly forming bone), 17 and long-term use of bisphosphonate increases the risk of osteonecrosis in the jaw. 18 A short peptide sequence of repetitive aspartic acid (4-10 amino acids) has been shown to interact exclusively with bone in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Liu¹,

Zeng²,

Shi

et al. 2017

IJN

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Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

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“…Nanocarriers to deliver therapeutic agents, including small drugs, proteins, and genetic molecules have been significantly developed to treat diseases and to restore the functions of damaged tissues. The delivery carriers need to possess several general properties, including a high loading capacity and controlled and sustained delivery in order to enable therapeutic function at clinically relevant doses . Among the delivery vehicles, silica‐based inorganic nanocarriers have been promising candidates, due to their cell and tissue compatibility, cellular uptake capacity, and the tunable physicochemical properties, like surface functionality and control over various sizes and shapes.…”

Section: Introductionmentioning

confidence: 99%

Delivery of Small Genetic Molecules through Hollow Porous Nanoparticles Silences Target Gene and in Turn Stimulates Osteoblastic Differentiation

Kim

Singh

Patel

et al. 2016

Part & Part Syst Charact

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Nanocarriers are one of the key elements to improve the therapeutic potential of signaling molecules, including genes for the disease treatment and tissue repair. Here, a nanocarrier system is reported that delivers genetic molecule small interference RNA (siRNA) for osteoblastic stimulation. For this, a hollow form of mesoporous silica nanoshell (MSns) is designed to load and release siRNA to silence Plekho‐1 gene. In particular, a pressure‐induced loading method is effective in enhancing the incorporation of siRNA within a hollow space; a loading level attained ≈30% is almost three times higher than that of a non‐hollow form. Furthermore, the release of siRNA from the nanocarriers is highly sustainable; continued over 18 d in a diffusion‐controlled manner, in striking contrast to the rapid release (3 d) from a non‐hollow form. The nanocarriers exhibit excellent cell viability, and the siRNA‐nanocarrier complexes are efficiently internalized to osteoblastic cells (uptake level over 90%). The intracellular delivery suppresses the target gene Plekho‐1 expression down to 20%, which in turn up‐regulates the expression of osteoblast transcriptional factors (Runx2 and Smad2), demonstrating an effective gene delivery system for bone repair.

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Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

Cited by 19 publications

References 44 publications

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Delivery of Small Genetic Molecules through Hollow Porous Nanoparticles Silences Target Gene and in Turn Stimulates Osteoblastic Differentiation

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Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

Cited by 19 publications

References 44 publications

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (&epsilon;-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Delivery of Small Genetic Molecules through Hollow Porous Nanoparticles Silences Target Gene and in Turn Stimulates Osteoblastic Differentiation

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Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone