Osteogenic, anti-osteoclastogenic and immunomodulatory properties of a strontium-releasing hybrid scaffold for bone repair

Lourenço, Ana Henriques; Torres, Ana Luísa; Vasconcelos, Daniela P.; Ribeiro-Machado, Cláudia; Barbosa, Judite N.; Barbosa, Mário A.; Barrias, Cristina C.; Ribeiro, Cristina

doi:10.1016/j.msec.2019.02.053

Cited by 66 publications

(51 citation statements)

References 67 publications

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“…Previous studies have reported that strontium can have immunomodulatory properties [25]. Lourenco et al found that fewer inflammatory cells were recruited to a strontium implant site than to that of a sham operation in rodents [25]. Similar to our study, they obtained their results within around two weeks of implantation.…”

Section: Longitudinal Nf-κb Activity During Fracture Healingsupporting

confidence: 89%

“…On the other hand, NF-κB activity tended to decrease in the latter phase of fracture healing in both the non-scaffolded as well as the β-TCP-scaffolded group, but in the strontium (+ Sr) group, by contrast, NF-κB activity shows a significant increase beginning around day 40 after the fracture. The immunomodulatory properties of Sr is discussed in some studies [25,33], but as far as we know, such an anti-inflammatory effect of strontium has never been reported in a study featuring longitudinal monitoring. Acute inflammation is a crucial biological process for tissue homeostasis in the early phase of fracture healing.…”

Section: Longitudinal Nf-κb Activity During Fracture Healingmentioning

confidence: 99%

“…Three weeks after fracture, NF-κB activity in the β-TCP group is tendentially higher than it is in the β-TCP group, with strontium scaffolds (+ Sr), and this would indicate that strontium has anti-inflammatory effects during the early phase of fracture healing. Previous studies have reported that strontium can have immunomodulatory properties [25]. Lourenco et al found that fewer inflammatory cells were recruited to a strontium implant site than to that of a sham operation in rodents [25].…”

Section: Longitudinal Nf-κb Activity During Fracture Healingmentioning

confidence: 99%

“…Nevertheless, the oral application of strontium ranelate increases the risk of deep venous thromboembolism due to systemic distribution and, therefore, should be avoided in patients with the increased risk of stroke and ischemic cardiac disease [24]. The exact mechanism behind the action of strontium still needs to be elucidated [25,26].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model

Tohidnezhad

Kubo

Lichte

et al. 2020

IJMS

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It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed β-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the β-TCP + Sr group in the latter stage (day 40–60). VEGFR-2 activity increased in the + Sr group from days 0–15 but decreased and showed significantly less activity than the β-TCP and non-scaffold groups from days 40–60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the β-TCP group, whereas the percentage of osseous tissue formation in the β-TCP group was significantly higher than in the β-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.

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Section: Longitudinal Nf-κb Activity During Fracture Healingsupporting

confidence: 89%

Section: Longitudinal Nf-κb Activity During Fracture Healingmentioning

confidence: 99%

Section: Longitudinal Nf-κb Activity During Fracture Healingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model

Tohidnezhad

Kubo

Lichte

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Similarly, other studies with Sr had shown similar burst release profiles of Sr ions and that incorporation of Sr ions had significant pro-osteogenic potential such as inducing higher amount of hydroxyapatite layer formation [38]. In similar studies, the presence of Sr was not only found to stimulate pre-osteoblastic cells, Sr was also found to have anti-inflammatory responses which were a critical component to have as the main problem of nano- and micro-sized particles application is in its immune system activation [39]. In addition, numerous reports had indicated that Si, being a trace element, had a huge role to play in enhancing bone growth and Si had been widely applied to biomaterials due to its osteogenic potential.…”

Section: Resultsmentioning

confidence: 90%

Effect of Strontium Substitution on the Physicochemical Properties and Bone Regeneration Potential of 3D Printed Calcium Silicate Scaffolds

Chiu

Shie

Lin

et al. 2019

IJMS

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In this study, we synthesized strontium-contained calcium silicate (SrCS) powder and fabricated SrCS scaffolds with controlled precise structures using 3D printing techniques. SrCS scaffolds were shown to possess increased mechanical properties as compared to calcium silicate (CS) scaffolds. Our results showed that SrCS scaffolds had uniform interconnected macropores (~500 µm) with a compressive strength 2-times higher than that of CS scaffolds. The biological behaviors of SrCS scaffolds were assessed using the following characteristics: apatite-precipitating ability, cytocompatibility, proliferation, and osteogenic differentiation of human mesenchymal stem cells (MSCs). With CS scaffolds as controls, our results indicated that SrCS scaffolds demonstrated good apatite-forming bioactivity with sustained release of Si and Sr ions. The in vitro tests demonstrated that SrCS scaffolds possessed excellent biocompatibility which in turn stimulated adhesion, proliferation, and differentiation of MSCs. In addition, the SrCS scaffolds were able to enhance MSCs synthesis of osteoprotegerin (OPG) and suppress macrophage colony-stimulating factor (M-CSF) thus disrupting normal bone homeostasis which led to enhanced bone formation over bone resorption. Implanted SrCS scaffolds were able to promote new blood vessel growth and new bone regeneration within 4 weeks after implantation in critical-sized rabbit femur defects. Therefore, it was shown that 3D printed SrCS scaffolds with specific controllable structures can be fabricated and SrCS scaffolds had enhanced mechanical property and osteogenesis behavior which makes it a suitable potential candidate for bone regeneration.

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Scaffold Fabrication Technologies and Structure/Function Properties in Bone Tissue Engineering

Collins

Ren

Young

et al. 2021

Adv Funct Materials

492

254

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Bone tissue engineering (BTE) is a rapidly growing field aiming to create a biofunctional tissue that can integrate and degrade in vivo to treat diseased or damaged tissue. It has become evident that scaffold fabrication techniques are very important in dictating the final structural, mechanical properties, and biological response of the implanted biomaterials. A comprehensive review of the current accomplishments on scaffold fabrication techniques, their structure, and function properties for BTE is provided herein. Different types of biomaterials ranging from inorganic biomaterials to natural and synthetic polymers and related composites for scaffold processing are presented. Emergent scaffolding techniques such as electrospinning, freeze-drying, bioprinting, and decellularization are also discussed. Strategies to improve vascularization potential and immunomodulation, which is considered a grand challenge in BTE scaffolding, are also presented.

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Osteogenic, anti-osteoclastogenic and immunomodulatory properties of a strontium-releasing hybrid scaffold for bone repair

Cited by 66 publications

References 67 publications

Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model

Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model

Effect of Strontium Substitution on the Physicochemical Properties and Bone Regeneration Potential of 3D Printed Calcium Silicate Scaffolds

Scaffold Fabrication Technologies and Structure/Function Properties in Bone Tissue Engineering

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