The healing of critical-sized femoral segmental bone defects in rabbits using baculovirus-engineered mesenchymal stem cells

Lin, Chin-Yu; Chang, Yu‐Han; Lin, Kun‐Ju; Yen, Tzu‐Chen; Tai, Ching‐Lung; Chen, Chi Yuan; Lo, Wen-Hsin; Hsiao, Ing‐Tsung; Hu, Yu‐Chen

doi:10.1016/j.biomaterials.2010.01.030

Cited by 81 publications

(52 citation statements)

References 43 publications

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“…Unfortunately, when implanted in the femoral window defects it acted as a barrier, separating the transplanted and endogenous cells. Insufficient vascularisation for effective mass transport of oxygen, nutrients and waste products through the scaffold has been documented as an obstacle to integration of cellseeded polymeric scaffolds into native bone in vivo (Lin et al, 2010). The angiogenic properties of VEGF are well recognised in both bone development (Carlevaro et al, 2000) and bone repair (Street et al, 2002;Uchida et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects

Gao

Ej²,

Chua³

et al. 2013

eCM

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The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid. The cells remained metabolically active in scaffolds incubated in vitro for up to 15 days and differentiated into osteoblasts that deposited calcium-phosphate mineral into the scaffold, which was quantified using micro-computed tomographic (micro-CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded scaffolds were rapidly mineralised and integrated into host bone with administration of 10 ng of recombinant VEGF injected into the femoral canal at 4 days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects that did not receive a bolus dose of VEGF did not mineralise or integrate with native bone. The approach with MSC, hydrogels and a biologic factor already approved for human use warrants further pre-clinical investigation with a large animal model.

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Section: Discussionmentioning

confidence: 99%

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects

Gao

Ej²,

Chua³

et al. 2013

eCM

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“…Transduction of human MSCs with baculovirus carrying the BMP-2 expression cassette was able to trigger their differentiation into osteoblasts which, after implantation into the dorsal subcutis of nude mice, resulted in ectopic bone formation (Chuang et al, 2007). Furthermore, a more recent study performed in immunocompetent rabbits using allogeneic MSCs transduced with baculovirus expressing BMP-2 and VEGF showed how this approach can augment the healing of large femoral segmental bone defects (Lin et al, 2010a).…”

Section: Ex Vivo Transductionmentioning

confidence: 97%

How to avoid complement attack in baculovirus-mediated gene delivery

Ylä‐Herttuala

Airenne

2011

Journal of Invertebrate Pathology

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“…The rat was sacrificed by CO 2 asphyxiation following the guidelines of the Institutional Animal Care and Use Committee. The bone marrow (4-6 mL) was aspirated from the ventral ilium of SD rats (8 weeks old), and rMSCs were cultured as described by Lin et al 16 The stem cells were used for subsequent experiments. …”

Section: Alp Assaymentioning

confidence: 99%

Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers

Hsu

Lin²,

et al. 2016

IJN

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In this study, we developed biodegradable sheath-core-structured drug-eluting nanofibers for sustainable delivery of antibiotics (vancomycin and ceftazidime) and recombinant human bone morphogenetic protein (rhBMP-2) via electrospinning. To prepare the biodegradable sheath-core nanofibers, we first prepared solutions of poly( d , l )-lactide- co -glycolide, vancomycin, and ceftazidime in 1,1,1,3,3,3-hexafluoro-2-propanol and rhBMP-2 in phosphate-buffered solution. The poly( d , l )-lactide- co -glycolide/antibiotics and rhBMP-2 solutions were then fed into two different capillary tubes controlled by two independent pumps for coaxial electrospinning. The electrospun nanofiber morphology was observed under a scanning electron microscope. We further characterized the in vitro antibiotic release from the nanofibers via high-performance liquid chromatography and that of rhBMP-2 via enzyme-linked immunosorbent assay and alkaline phosphatase activity. We showed that the biodegradable coaxially electrospun nanofibers could release high vancomycin/ceftazidime concentrations (well above the minimum inhibition concentration [MIC] 90 ) and rhBMP-2 for >4 weeks. These experimental results demonstrate that novel biodegradable nanofibers can be constructed with various pharmaceuticals and proteins for long-term drug deliveries.

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The healing of critical-sized femoral segmental bone defects in rabbits using baculovirus-engineered mesenchymal stem cells

Cited by 81 publications

References 43 publications

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects

How to avoid complement attack in baculovirus-mediated gene delivery

Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers

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