A review of mouse critical size defect models in weight bearing bones

Harris, Jonathan S.; Bemenderfer, Thomas B.; Wessel, A. R.; Kacena, Melissa A.

doi:10.1016/j.bone.2013.02.002

Cited by 43 publications

(35 citation statements)

References 43 publications

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“…This result was consistent with Jiang et al .’s report that the presence of fibrin increased stiffness of porous PEG hydrogels relative to control porous hydrogels, and the compressive modulus of the hydrogels increased with the concentration of the fibrinogen [22]. In the in vivo study, the CLF hydrogels using 200s of UV was selected because the CLF hydrogels were mechanically sufficient to be press-fitted into the critical size segmental defects in femur while remaining structural integrity and stabilizing interface, potentially enhancing bone bridging and regeneration as a promising synthetic bone substitute [1, 33]. …”

Section: Discussionmentioning

confidence: 99%

“…Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor and plays an important role in bone regeneration by stimulating endochondral ossification via chemotaxis, migration, proliferation and osteogenic differentiation of mesenchymal stem cells [1–4]. However, BMP-2 administered in the form of a buffer solution has a short biological half-life, rapid clearance, potential harmful side effects, and is very costly in systematic delivery [2, 5–6].…”

Section: Introductionmentioning

confidence: 99%

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Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

et al. 2014

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The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus, and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100, and 500 ng/ml) in vitro using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. The effect of BMP-2 containing CLF gels (0, 0.5, 1, 2, and 5μg) on bone formation was evaluated using rat critical size segmental bone defects for 4 weeks. FTIR spectra and SEM images showed chemical and structural changes by addition of fibrinogen into chitosan-lactide copolymer. Incorporation of fibrinogen molecules significantly increased compressive modulus of the hydrogels. In vitro BMP-2 release study showed initial burst releases from the CLF hydrogels followed by sustained releases, regardless of the concentration of the BMP-2 over 4 weeks. Cells in all groups were viable in the presence of the hydrogels regardless of BMP-2 doses, indicating non-cytotoxicity of hydrogels. Alkaline phosphate activity and mineralization of cells exhibited dose dependence on BMP-2 containing CLF hydrogels. Radiographs, microcomputed tomography, and histology confirmed that the BMP-2 containing CLF hydrogels prompted neo-osteogenesis and accelerated healing of the defects in a dose-dependent manner. Thus the CLF hydrogel is a promising delivery system of growth factors for bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

et al. 2014

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“…A vertical incision was made above the bilateral knee joint to expose the lower femoral joint. A cylindrical hole‐like defect (diameter 4 mm, depth 5 mm) was drilled on the distal femoral condyle . During surgery, we did the operation meticulously to avoid any damage on the patellar groove and the outside of the femoral bone.…”

Section: Methodsmentioning

confidence: 99%

Osteogenic potential and synergistic effects of growth factors delivered from a bionic composite system

Chen

Gomez

Zuo

et al. 2015

J Biomedical Materials Res

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Previous research has raised substantial controversy over the synergistic effects of exogenous growth factors, BMP-2 and bFGF, when used together for the treatment of bony defects. Thus, this study evaluated the effects of BMP-2 and bFGF at specified dose ratio composited with n-HA/PU40, a porous scaffold material, for repairing femoral defect in rats. Four weeks after implantation of this composite system, tissue specimens were collected for histological, immunohistochemical examinations, and µ-CT scanning. The results showed that the group DUAL/BMSCs with both the factors had better effect on repairing bone defects than the other four groups in terms of new bone formation and bone-scaffold bonding, suggesting crosstalk between these growth factors during early bone regeneration. This work demonstrates that provided that there is effective contact between cells and active proteins in the defect area, the controlled release of bFGF and BMP-2 have positive synergistic effects on early bone formation in the defect area. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 659-668, 2016.

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“…However, if the defect size is large enough then the bone cannot heal itself. The minimum length of the bone, where if left untreated, there will be no union is termed critical sized bone defect and can be different depending on the location of injury or the animal model used [16]. Such defects lack sufficient blood supply for callous formation and need surgical intervention to provide mechanical support and promote bone repair.…”

Section: Bone Repair Biology and Current Challengesmentioning

confidence: 99%

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

Agarwal

Garcı́a

2015

Advanced Drug Delivery Reviews

638

399

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Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair.

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A review of mouse critical size defect models in weight bearing bones

Cited by 43 publications

References 43 publications

Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

Osteogenic potential and synergistic effects of growth factors delivered from a bionic composite system

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

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