Multicellularity-interweaved bone regeneration of BMP-2-loaded scaffold with orchestrated kinetics of resorption and osteogenesis

Niu, Haoyi; Ma, Yifan; Wu, Guangyu; Duan, Bing; Wang, Ying; Yuan, Yuan; Liu, Changsheng

doi:10.1016/j.biomaterials.2019.05.027

Cited by 54 publications

(50 citation statements)

References 34 publications

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“…Regarding the effects of BMP members on osteoclastogenesis, most data were obtained for BMP2 and BMP5‐7, but the results were conflicting . However, little is known regarding the effects of BMP9 on osteoclast differentiation in bone marrow mononuclear cells (BMMs), the origin of osteoclasts or the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling

Zhou

Yang

Jing

et al. 2020

Journal of Bone and Mineral Research

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Bone remodeling is dynamic and is tightly regulated through bone resorption dominated by osteoclasts and bone formation dominated by osteoblasts. Imbalances in this process can cause various pathological conditions, such as osteoporosis. Bone morphogenetic protein 9 (BMP9), a biomolecule produced and secreted by the liver, has many pharmacological effects, including anti-liver fibrosis, antitumor, anti-heart failure, and antidiabetic activities. However, the effects of BMP9 on the regulation of osteoblast and osteoclast functions and the underlying molecular mechanism(s) have not yet been investigated. In this study, BMP9 increased the expression of osteoblastogenic gene markers, such as ALP, Cola1, OCN, RUNX2, and OSX, and ALP activity in MC3T3-E1 cells by upregulating LGR6 and activating the Wnt/β-catenin pathway. BMP9 also suppressed receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages (BMMs) by inhibiting the Akt-NF-κB-NFATc1 pathway. More importantly, in an ovariectomy (OVX) mouse model, BMP9 attenuated bone loss and improved bone biomechanical properties in vivo by increasing bone-forming activity and suppressing bone resorption activity. Accordingly, our current work highlights the dual regulatory effects that BMP9 exerts on bone remodeling by promoting bone anabolic activity and inhibiting osteoclast differentiation in OVX mice.

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Section: Introductionmentioning

confidence: 99%

BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling

Zhou

Yang

Jing

et al. 2020

Journal of Bone and Mineral Research

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“…There are many forms of BAG used in bone tissue engineering, such as particles [164], coating [165], bone cement [166] and scaffolds [25]. At the same time, BAG can also be used to load drugs [167] and biological factors [168]. Excitingly, there are already several particulate BAG products in clinical use, such as PerioGlas®, NovaBone® and BonAlive®.…”

Section: Bioactive Glassesmentioning

confidence: 99%

“…For the degradation of BAG scaffolds, some scholars have also made in-depth research. Recently, Niu et al [168] made an in-depth evaluation of the resorption/osteogenesis properties of the rhBMP-2-loaded trimodal macro/micro/nano-porous bioactive glass scaffold (TMS-rhBMP-2). The in vivo results of rabbit radius large segmental defect model show that the TMS-rhBMP-2 has similar biodegradation rate (2.43, 1.81, 0.54 and 0.32%/day) and bone formation rate (2.85, 2.14, 0.78 and 0.46%/day) at 0-1, 1-4, 4-8 and 8-12 week.…”

Section: Bioactive Glassesmentioning

confidence: 99%

Biodegradable materials for bone defect repair

et al. 2020

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Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the twenty-first century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.

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“…In a typical bone regeneration process, scaffolds placed in bone defect sites can lead to rapid initiation of efficient cell recruitment, adhesion, proliferation, and osteodifferentiation, which are important for bone regeneration and bone remodeling. 54,55 Eight weeks after treatment, the tibia plateau of the VCM-NPs/Gel group appeared flatter than that of the VCM/Gel group. The images of the 3D reconstruction in Figure 8C indicate a progressive increase in bone volume at the end of the 8th week post-treatment with VCM/Gel, VCM-NPs/Gel, and VCS, while it tended toward bone loss in the model groups.…”

Section: Radiographic Datamentioning

confidence: 99%

<p>Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis</p>

Jin¹,

Zhang²,

Shen³

et al. 2020

IJN

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Purpose: Osteomyelitis, particularly chronic osteomyelitis, remains a major challenge for orthopedic surgeons. The traditional treatment for osteomyelitis, which involves antibiotics and debridement, does not provide a complete solution for infection and bone repair. Antibiotics such as vancomycin (VCM) are commonly used to treat osteomyelitis in clinical settings. VCM use is limited by a lack of effective delivery methods that provide sustained, high doses to entirely fill irregular bone tissue to treat infections. Methods: We engineered a chitosan (CS)-based thermosensitive hydrogel to produce a VCM-nanoparticle (NPs)/Gel local drug delivery system. The VCM-NPs were formed with quaternary ammonium chitosan and carboxylated chitosan nanoparticles (VCM-NPs) by positive and negative charge adsorption to enhance the encapsulation efficiency and drug loading of VCM, with the aim of simultaneously preventing infection and repairing broken bones. This hydrogel was evaluated in a rabbit osteomyelitis model. Results: The VCM-NPs had high encapsulation efficiency and drug loading, with values of 60.1±2.1% and 24.1±0.84%, respectively. When embedded in CS-Gel, the VCM-NPs maintained their particle size and morphology, and the injectability and thermosensitivity of the hydrogel, which were evaluated by injectability test and rheological measurement, were retained. The VCM-NPs/Gel exhibited sustained release of VCM over 26 days. In vitro tests revealed that the VCM-NPs/Gel promoted osteoblast proliferation and activity against Staphylococcus aureus. In vivo, VCM-NPs/Gel (with 10 mg vancomycin per rabbit) was used to treat rabbits with osteomyelitis. The VCM-NPs/Gel showed excellent anti-infection properties and accelerating bone repair under osteomyelitis conditions. Conclusion: The reported multifunctional NPs hydrogel system for local antibiotic delivery (VCM-NPs/Gel) showed bone regeneration promotion and anti-infection properties, demonstrating significant potential as a scaffold for effective treatment of osteomyelitis.

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Multicellularity-interweaved bone regeneration of BMP-2-loaded scaffold with orchestrated kinetics of resorption and osteogenesis

Cited by 54 publications

References 34 publications

BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling

BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling

Biodegradable materials for bone defect repair

<p>Injectable Chitosan-Based Thermosensitive Hydrogel/Nanoparticle-Loaded System for Local Delivery of Vancomycin in the Treatment of Osteomyelitis</p>

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