Local controlled release of simvastatin and PDGF from core/shell microspheres promotes bone regeneration in vivo

Yan, Mingming; Ni, Jiangdong; Shen, Hongwei; Song, Deye; Ding, Muliang; Huang, Jun

doi:10.1039/c7ra01503h

Cited by 11 publications

(4 citation statements)

References 32 publications

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“…More importantly, cell viability, proliferation, and osteogenic differentiation ability were well preserved during the electrosraying process. (Zhang & He, ) Similar to our previous reports, significantly enhanced osteogenesis was achieved using the electrospraying technology (Yan, Ni, Shen, Song, & Ding, ).…”

Section: Discussionsupporting

confidence: 82%

Dual delivery of encapsulated BM‐MSCs and BMP‐2 improves osteogenic differentiation and new bone formation

Kong

Zhao

Liu

et al. 2019

J Biomedical Materials Res

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Stem cell-based therapies provide a promising approach for bone repair. In the present work, we developed a novel 3D vehicle system for dual-delivery of encapsulated bone marrow mesenchymal stem cells (BM-MSCs) and bone morphogenetic protein-2 (BMP-2) for treatment of large bone defects. The vehicle system consists of sodium alginate microcapsules and polylactic acid (PLLA) microspheres. BM-MSCs are encapsulated in the microcapsules, and BMP-2 proteins are encapsulated in the PLLA microspheres. This vehicle system acted as a multicore structure for sustained release of BMP-2, which enabled pulsed dosing induction of osteogenic differentiation of the co-embedded BM-MSCs. in vitro experiments showed that the loaded BMP-2 was constitutively released up to 30 days. Bioactivity of the incorporated BMP-2 in the microspheres was preserved and osteogenic differentiation of the BM-MSCs in the microcapsules was improved. In vivo, osteogenesis studies demonstrated that satisfactory degree of repair of a rat calvarial defect was achieved with the delivery of either encapsulated BM-MSCs alone or encapsulated BMP-2 alone.Transplantation of encapsulated both BM-MSCs and BMP-2 exhibited the greatest repair potential following 4-or 8-weeks treatment. In conclusion, microencapsulation of BM-MSCs and BMP-2 promoted the maturity of newly generated bone and improved new bone formation. Transplantation of BM-MSCs and BMP-2 in our novel 3-D vehicle system is a promising strategy for regenerative therapies of large bone defects.

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Section: Discussionsupporting

confidence: 82%

Dual delivery of encapsulated BM‐MSCs and BMP‐2 improves osteogenic differentiation and new bone formation

Kong

Zhao

Liu

et al. 2019

J Biomedical Materials Res

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“…Therefore, incorporating simvastatin into the core of a core−shell microsphere provides a stable, sustained release profile because the shell acts as a barrier. 129 Yan et al 130 produced microspheres with poly-L-lactide (PLLA) cores that were loaded with simvastatin and alginate shells encapsulated with platelet-derived growth factor. The simvastatin in the inner layer exhibited a release pattern that was nearly zero-order over the course of 40 days.…”

Section: Simvastatin-loaded Drug Delivery Systemsmentioning

confidence: 99%

Simvastatin-Incorporated Drug Delivery Systems for Bone Regeneration

Jin

Cui

et al. 2021

ACS Biomater. Sci. Eng.

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Local drug delivery systems composed of biomaterials and osteogenic substances provide promising strategies for the reconstruction of large bone defects. In recent years, simvastatin has been studied extensively for its pleiotropic effects other than lowering of cholesterol, including its ability to induce osteogenesis and angiogenesis. Accordingly, several studies of simvastatin incorporated drug delivery systems have been performed to demonstrate the feasibility of such systems in enhancing bone regeneration. Therefore, this review explores the molecular mechanisms by which simvastatin affects bone metabolism and angiogenesis. The simvastatin concentrations that promote osteogenic differentiation are analyzed. Furthermore, we summarize and discuss a variety of simvastatin-loaded drug delivery systems that use different loading methods and materials. Finally, current shortcomings of and future development directions for simvastatin-loaded drug delivery systems are summarized. This review provides various advanced design strategies for simvastatin-incorporated drug delivery systems that can enhance bone regeneration.

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“…15 Furthermore, local controlled release of simvastatin and platelet-derived growth factor from core−shell microspheres promotes bone regeneration. 16 A recent study reported by our research group demonstrated that the dual delivery of simvastatin along with dexamethasone from the bioinspired scaffold has promoted early osteogenesis and angiogenesis. 17 Therefore, biomaterial-based core−shell microgels were fabricated in the present study in order to control the release of simvastatin and BMP-2 in a sequential manner.…”

Section: Introductionmentioning

confidence: 99%

“…In one study, a core–shell hydrogel scaffold was designed with BMP-2 in the core and cobalt ions (as an angiogenic factor) in the shell, where cobalt was released within 7 days while the release of BMP-2 continued for 3–4 weeks . Furthermore, local controlled release of simvastatin and platelet-derived growth factor from core–shell microspheres promotes bone regeneration . A recent study reported by our research group demonstrated that the dual delivery of simvastatin along with dexamethasone from the bioinspired scaffold has promoted early osteogenesis and angiogenesis .…”

Section: Introductionmentioning

confidence: 99%

Single-Step Fabrication of Core–Shell Microgels for the Controlled Release of rhBMP-2 and Simvastatin to Induce Osteogenesis

Meena

Rather

Vasita

2020

ACS Appl. Polym. Mater.

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Dual delivery of bioactive molecules (drugs and growth factors) has been attempted to enhance multiple processes during tissue regeneration. For bone tissue engineering, many attempts have been made to enhance osteogenesis coupled angiogenesis, which plays a major role during the bone regeneration process. In this study, core−shell microgels were fabricated for controlled release of recombinant human bone morphogenetic protein 2 (rhBMP-2) and simvastatin from the core and shell, respectively. The microgels were formed with a discrete core and shell structure. The Fourier transform infrared analysis demonstrated the composition of microgel, whereas swelling behavior demonstrated its rapid swelling property. Thermal properties demonstrated the ionic gelation in microgels, which minimizes the thermal degradation of polymers. The degradation study demonstrates that the core−shell structure of microgels was intact until 49 days under physiological conditions. The release profile demonstrates the sequential and controlled release of rhBMP-2 from the core and simvastatin from the shell of the microgels, respectively. The bioactivity of rhBMP-2 and simvastatin released from microgels was preserved as indicated by the alkaline phosphatase (ALP) activity assay. The cell proliferation of mouse preosteoblast (MC3T3-E1) cells and the live−dead staining assay demonstrated cytocompatibility of the microgels. Scanning electron microscopy images demonstrate that the microgels support adhesion of cells on the surface and promote extracellular matrix (ECM) production. The osteogenic differentiation of MC3T3-E1 cells demonstrated the synergistic effect of drugs and growth factors up to 21 days. The controlled and sustained release of simvastatin and rhBMP-2 induced higher mRNA and protein expressions of RUNX2, osteocalcin, and VEGF. The overall results demonstrate the effect of controlled release of rhBMP-2 and simvastatin from core−shell microgels to promote osteogenesis and angiogenesis.

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Local controlled release of simvastatin and PDGF from core/shell microspheres promotes bone regeneration in vivo

Cited by 11 publications

References 32 publications

Dual delivery of encapsulated BM‐MSCs and BMP‐2 improves osteogenic differentiation and new bone formation

Dual delivery of encapsulated BM‐MSCs and BMP‐2 improves osteogenic differentiation and new bone formation

Simvastatin-Incorporated Drug Delivery Systems for Bone Regeneration

Single-Step Fabrication of Core–Shell Microgels for the Controlled Release of rhBMP-2 and Simvastatin to Induce Osteogenesis

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