Subcutaneous tissue response and osteogenic performance of calcium phosphate nanoparticle-enriched hydrogels in the tibial medullary cavity of guinea pigs

Bongio, Matilde; Beucken, Jeroen J.J.P. van den; Nejadnik, M. Reza; Birgani, Zeinab Tahmasebi; Habibović, Pamela; Kinard, Lucas A.; Kasper, F. Kurtis; Mikos, Antonios G.; Leeuwenburgh, Sander C. G.; Jansen, John A.

doi:10.1016/j.actbio.2012.10.026

Cited by 22 publications

(18 citation statements)

References 34 publications

(42 reference statements)

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“…Similar results were also observed with previous HA-based nanoparticles, supporting the bioactivity and osteoinductivity of HA nanoparticles. 10–12,14 Compared pure silk particles, higher expression of osteocalcin occurred the silk-HA composite particles without the loading of BMP-2 which suggested that the upregulation of osteocalcin should be due to the HA existence. The controlled release of BMP-2 could also improve the upregulatation of osteocalcin.…”

Section: Resultsmentioning

confidence: 99%

“…These results suggested that the presence of HA further improved the biocompatibility of the nanocarriers, which was also revealed in previous studies. 10–12,27 Although further investigation was necessary, it was suggested that the organic-inorganic silk-HA composite structures, similar with natural bone microenvironment, provided better niche for the MSCs. Similar results was also found on silk-HA composite scaffolds, where the MSCs proliferated better on the composite scaffolds than on the pure silk scaffolds.…”

Section: Resultsmentioning

confidence: 99%

“…1–4 Different nanoscale materials that achieve controlled release of bioactive drugs have been reported for musculoskeletal tissue engineering, including polymeric nanoparticles consisting of micelles and dendrimers, and inorganic nanoparticles such as calcium phosphate and bioactive glasses. 5–9 Calcium phosphates (CaP), particularly hydroxyapatite (HA), have similar chemical and crystallographic structures with the inorganic components of bone in vivo and are used in orthopedic applications 10–12 Their excellent biocompatibility and osteo-conductivity make them important candidates for bone regeneration and the delivery of growth factors. 13–15 Different processes were developed to tune the morphology, size and structure of HA nanoparticles to improve drug loading and release properties.…”

Section: Introductionmentioning

confidence: 99%

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Bioactive natural protein–hydroxyapatite nanocarriers for optimizing osteogenic differentiation of mesenchymal stem cells

et al. 2016

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Improving the controlled release of bioactive growth factors to regulate cell behavior and tissue regeneration remains a need in tissue engineering and regenerative medicine. Inorganic and polymeric nanoparticles have been extensively fabricated as bioactive biomaterials with enhanced biocompatibility and effective carriers of therapeutic agents, however, challenges remain such as the achievement of high loading capacity and sustained release, and the bioactivity preservation of growth factors. Here, a multilayered, silk coated hydroxyapatite (HA) nanocarrier with drug loading-release capacity superior to pure silk or HA nanoparticles was developed. Bone morphogenetic protein-2 (BMP-2) was bound to the silk coatings with a high binding efficiency of 99.6%, significantly higher than that in silk or the HA nanoparticles alone. The release of BMP-2 was sustained in vitro over a period of 21 days without burst release. Compared with BMP-2 loaded silk or HA particles, bone mesenchymal stem cells (BMSCs) showed improved proliferation and osteogenesis when cultured with the BMP-2 loaded composite nanocarriers. Therefore, these silk-HA composite nanoparticles present a useful approach to designing bioactive nanocarrier systems with enhanced functions for bone tissue regeneration needs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bioactive natural protein–hydroxyapatite nanocarriers for optimizing osteogenic differentiation of mesenchymal stem cells

et al. 2016

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“…Both sides of the discs were coated for 15 min at 200 W, resulting in a visually complete layer of titanium roughly 50 nm thick. The elemental composition and distribution of the titanium coating was verified using electron dispersive spectroscopy (EDS), as previously described (Bongio et al, 2013). Briefly, samples were affixed to metal stubs and scanned by a scanning electron microscope (Philips XL30) equipped with an energy dispersive spectrometer (EDAX, Ametek).…”

Section: Methodsmentioning

confidence: 99%

Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs

Davison

Su²,

Yuan³

et al. 2015

eCM

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It has been reported that surface microstructural dimensions can influence the osteoinductivity of calcium phosphates (CaPs), and osteoclasts may play a role in this process. We hypothesised that surface structural dimensions of ≤ 1 μm trigger osteoinduction and osteoclast formation irrespective of macrostructure (e.g., concavities, interconnected macropores, interparticle space) or surface chemistry. To test this, planar discs made of biphasic calcium phosphate (BCP: 80 % hydroxyapatite, 20 % tricalcium phosphate) were prepared with different surface structural dimensions -either ~ 1 μm (BCP1150) or ~ 2-4 μm (BCP1300) -and no macropores or concavities. A third material was made by sputter coating BCP1150 with titanium (BCP1150Ti), thereby changing its surface chemistry but preserving its surface structure and chemical reactivity. After intramuscular implantation in 5 dogs for 12 weeks, BCP1150 formed ectopic bone in 4 out of 5 samples, BCP1150Ti formed ectopic bone in 3 out of 5 samples, and BCP1300 formed no ectopic bone in any of the 5 samples. In vivo, large multinucleated osteoclast-like cells densely colonised BCP1150, smaller osteoclast-like cells formed on BCP1150Ti, and osteoclast-like cells scarcely formed on BCP1300. In vitro, RAW264.7 cells cultured on the surface of BCP1150 and BCP1150Ti in the presence of osteoclast differentiation factor RANKL (receptor activator for NF-κB ligand) proliferated then differentiated into multinucleated osteoclast-like cells with positive tartrate resistant acid phosphatase (TRAP) activity. However, cell proliferation, fusion, and TRAP activity were all significantly inhibited on BCP1300. These results indicate that of the material parameters tested -namely, surface microstructure, macrostructure, and surface chemistry -microstructural dimensions are critical in promoting osteoclastogenesis and triggering ectopic bone formation.

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“…Unlike solid scaffolds, hydrogels are fabricated to contain a large amount of water and are characterized by swelling through increasing the water content upon implantation in vivo . This highly hydrated state allows for the free diffusion of oxygen and nutrients into the scaffold, and thus provides an optimum environment for the new bone tissue ingrowth [189–193]. Hydrogels are synthesized by crosslinking the branches of hydrophilic polymers using a bridging agent; where the water content depends on the type and concentration of the molecules and the bridging agent [95].…”

Section: Bmp Delivery Systemsmentioning

confidence: 99%

Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration

2017

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Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not without reports of multiple complications and side effects. Aiming for optimization of the therapeutic efficacy and safety, efforts have been focused on improving the delivery of BMPs to lower the administered dose, localize the protein, and prolong its retention time at the site of action. A major challenge with these efforts is that the protein stability should be maintained. With this review we attempt to shed light on how the stability of BMPs can be affected in the formulation and delivery processes. We first provide a short overview of the current standing of the complications experienced with BMP products. We then discuss the different delivery parameters studied in association with BMPs, and their influence on the efficacy and safety of BMP treatments. In particular, the literature addressing the stability of BMPs and their possible interactions with components of the delivery system as well as their sensitivity to conditions of the formulation process is reviewed. In summary, recent developments in the fields of bioengineering and biopharmaceuticals suggest that a good understanding of the relationship between the formulation/delivery conditions and the stability of growth factors such as BMPs is a prerequisite for a safe and effective treatment.

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Subcutaneous tissue response and osteogenic performance of calcium phosphate nanoparticle-enriched hydrogels in the tibial medullary cavity of guinea pigs

Cited by 22 publications

References 34 publications

Bioactive natural protein–hydroxyapatite nanocarriers for optimizing osteogenic differentiation of mesenchymal stem cells

Bioactive natural protein–hydroxyapatite nanocarriers for optimizing osteogenic differentiation of mesenchymal stem cells

Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs

Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration

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