Repair of segmental bone defects in rabbit tibiae using a complex of β-tricalcium phosphate, type I collagen, and fibroblast growth factor-2

Komaki, Hirokazu; Tanaka, Takaaki; Chazono, Masaaki; Kikuchi, Toru

doi:10.1016/j.biomaterials.2006.05.031

Cited by 127 publications

(101 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment of complex fractures and other bone defects caused by high-energy trauma, disease, developmental deformity, revision surgery, and tumor resection have been improved due to advances in surgical techniques, orthopaedic implants, and perioperative management [12,16,25,27,38,52]. However, detrimental bone healing conditions (eg, comorbidities such as diabetes mellitus, infections, improper vascular supply, etc), suboptimal surgical techniques, or biomechanical instability can result in impaired healing capacity (eg, nonunions, large remaining bone gaps) [39].…”

Section: Introductionmentioning

confidence: 99%

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Balmayor

Feichtinger

Azevedo

et al. 2009

Clin Orthop Relat Res

View full text Add to dashboard Cite

BMP-2 is currently administered clinically using collagen matrices often requiring large amounts of BMP-2 due to burst release over a short period of time. We developed and tested a novel injectable drug delivery system consisting of starch-poly-e-caprolactone microparticles for inducing osteogenesis and requiring smaller amounts of BMP-2. We evaluated BMP-2 encapsulation efficiency and the in vitro release profile by enzyme-linked immunosorbent assay. BMP-2 was rapidly released during the first 12 hours, followed by sustained release for up to 10 days. We then evaluated the osteogenic potential of dexamethasone (standard osteogenic induction agent) and BMP-2 after incorporation and during release using an osteo/myoblast cell line (C2C12). Alkaline phosphatase activity was increased by released BMP-2. Mineralization occurred after stimulation with BMP-2-loaded microparticles. A luciferase assay for osteocalcin promoter activity showed high levels of activity upon treatment with BMP-2-loaded microparticles. In contrast, no osteogenesis occurred in C2C12 cells using dexamethasone-loaded microparticles. However, human adipose stem cells exposed to the microparticles produced high amounts of alkaline phosphatase. The data suggest starch-poly-e-caprolactone microparticles are suitable carriers for the incorporation and controlled release of glucocorticoids and growth factors. Specifically, they reduce the amount of BMP-2 needed and allow more sustained osteogenic effects.

show abstract

Section: Introductionmentioning

confidence: 99%

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Balmayor

Feichtinger

Azevedo

et al. 2009

Clin Orthop Relat Res

View full text Add to dashboard Cite

show abstract

“…These studies led to the wide use of FGF2 as a therapeutic agent for promoting bone regeneration in animal models (Fei et al 2013). Typically, the local implantation of FGF2 impregnated in a gelatin hydrogel or a molecular scaffold or the injection of chemically controlled FGF2-secreting cells was found to promote bone healing in cranial or long bone defects (Chen et al 2004;Komaki et al 2006;Kodama et al 2009;Kawaguchi et al 2010;Kwan et al 2011). However, the effects on bone healing are dependent on the dose used, the time of application, and the duration of FGF treatment Fei et al 2013).…”

Section: Fgf and Bone Regenerationmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

View full text Add to dashboard Cite

Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.

show abstract

“…2 Effects of HGF on bone healing b-TCP and collagen promotes healing of bone fractures after a tibial osteotomy, compared with the material without PDGF-BB [6]. In rabbits, FGF-2 in a mixture of b-TCP and collagen facilitates healing of segmental bone defects [17]. BMP-2 in gelatin-based sponges containing b-TCP has higher osteoinductive activity at bone-defect sites than sponges that do not contain BMP-2 [16].…”

Section: Discussionmentioning

confidence: 99%

“…It has excellent osteoconduction and resorbability when filling bone defects [15]. b-TCP is also a potential carrier for local delivery of polypeptide growth factors, including BMP-2 [16], FGF-2 [17], and PDGF [6], to promote bone healing. However, the effects of a complex of b-TCP and HGF on bone healing have yet to be addressed.…”

Section: Introductionmentioning

confidence: 99%

Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

Goshima

Nakase

et al. 2012

Journal of Orthopaedic Science

View full text Add to dashboard Cite

Background Segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on bone tissue engineering. Clinical studies are ongoing to address application of hepatocyte growth factor (HGF) for treatment of some diseases; however, the use of HGF in bone tissue engineering has not been addressed. This study was performed to evaluate the effect of HGF in a complex of b-tricalcium phosphate (b-TCP) and collagen in repairing segmental bone defects. Methods Segmental bone defects 5 mm long were created in the middle of the tibial shafts of rabbits. The defect was stabilized with external fixators and implanted with a complex of b-TCP granules and collagen, with or without 100 lg recombinant human HGF. Biweekly, bone regeneration and b-TCP resorption were assessed radiographically and histologically. At 4 and 8 weeks, bone regeneration was evaluated by use of micro-computed tomography and mechanical tests. Results Compared with the bone tissue treated with b-TCP and collagen, mineralization, angiogenesis, new bone formation, and absorption of b-TCP were promoted 4 weeks postoperatively by treatment with HGF in the b-TCP and collagen group. These changes were associated with promoting biomechanical regeneration. By 8 weeks, the formation of bone marrow in newly generated bone and absorption of the b-TCP granules were completed in a shorter period by combining HGF with b-TCP and collagen, compared with tissues without HGF. Conclusions The combined application of HGF in a b-TCP and collagen matrix promoted histological bone healing and augmented mechanical strength of the healing bone, particularly in the early stages. The combined use of HGF and b-TCP for treatment of bone defects made a substantial difference.

show abstract

Repair of segmental bone defects in rabbit tibiae using a complex of β-tricalcium phosphate, type I collagen, and fibroblast growth factor-2

Cited by 127 publications

References 41 publications

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Starch-poly-є-caprolactone Microparticles Reduce the Needed Amount of BMP-2

Fibroblast growth factor signaling in skeletal development and disease

Repair of segmental bone defects in rabbit tibia promoted by a complex of β-tricalcium phosphate and hepatocyte growth factor

Contact Info

Product

Resources

About