PLGA-Based Microparticles for the Sustained Release of BMP-2

Kirby, Giles T. S.; White, Lisa J.; Rahman, Cheryl V.; Cox, Helen C.; Qutachi, Omar; Rose, Felicity R. A. J.; Hutmacher, Dietmar W.; Shakesheff, Kevin M.; Woodruff, Maria A.

doi:10.3390/polym3010571

Cited by 66 publications

(63 citation statements)

References 44 publications

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“…Injectable biodegradable scaffolds have many benefits including minimally invasive delivery and the ability to deliver drugs in vitro (Rahman et al, 2012;Gould et al, 2013; and drugs, cells and proteins locally to the fracture site (Ginty et al, 2008;Kirby et al, 2011). They have also been shown to reduce the length of hospital stay; need for rehabilitation, postoperative morbidity and readmission rate and consequently the associated costs are significantly reduced (Ilan and Ladd, 2003).…”

Section: Introductionmentioning

confidence: 99%

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

McLaren

White²,

Cox³

et al. 2014

eCM

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Open fractures are at risk of serious infection and, if infected, require several surgical interventions and courses of systemic antibiotics. We investigated a new injectable formulation that simultaneously hardens in vivo to form a porous scaffold for bone repair and delivers antibiotics at high concentrations to the local site of infection. Duration of antimicrobial activity against Staphylococcus aureus was determined using the serial plate transfer test. Ultimate compressive strength and porosity of the material was measured with and without antibiotics. The material was evaluated in vivo in an ovine medial femoral condyle defect model contaminated with S. aureus. Sheep were sacrificed at either 2 or 13 weeks and the defect and surrounding bone assessed using micro-computed tomography and histology. Antimicrobial activity in vitro persisted for 19-21 days. Sheep with antibiotic-free material and bacteria became infected, while those with antibiotic-containing material and bacteria did not. Similarly, new bone growth was seen in uninoculated animals with plain polymer, and in those with antibiotic polymer with bacteria, but not in sheep with plain polymer and bacteria. The antibiotic-impregnated scaffolds were effective in preventing S. aureus infections whilst supporting bone growth and repair. If translated into clinical practice, this approach might reduce the need for systemic antibiotics.

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Section: Introductionmentioning

confidence: 99%

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

McLaren

White²,

Cox³

et al. 2014

eCM

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“…At the forefront of these technologies is the synthesis of particles for various applications in targeted drug delivery [1,2], growth factor delivery [3,4], gene therapy [5], medical imaging [6] and tissue engineering [7,8]. Delivery of drugs via nano or microparticles aims to reduce collateral damage to healthy tissues, extend the drug's availability and effectiveness at the site, and then finally it is hoped that the particles will degrade naturally after carrying out their function [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Design of extracellular protein based particles for intra and extra-cellular targeting

Omorphos

Kahn

Kalaskar

2015

Colloids and Surfaces B: Biointerfaces

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“…3,4 However, recombinant BMP-2 protein is expensive and rapidly degrades in vivo. 5,6 Gene therapy may provide an alternative method for delivery of BMP-2.…”

Section: Introductionmentioning

confidence: 99%

Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

Qiao

Zhang²,

Jin³

et al. 2013

IJN

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Abstract:Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/ PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3-15 µm diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.

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PLGA-Based Microparticles for the Sustained Release of BMP-2

Cited by 66 publications

References 44 publications

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

A biodegradable antibiotic-impregnated scaffold to prevent osteomyelitis in a contaminated in vivo bone defect model

Design of extracellular protein based particles for intra and extra-cellular targeting

Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

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