Growth Factor Interactions in Bone Regeneration

Kempen, Diederik H.R.; Creemers, Laura B.; Alblas, Jacqueline; Lu, Lichun; Verbout, Abraham J.; Yaszemski, Michael J.; Dhert, Wouter J.A.

doi:10.1089/ten.teb.2010.0176

Cited by 100 publications

(91 citation statements)

References 175 publications

(183 reference statements)

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“…21 For this reason, a number of investigators have explored the effects of the combined delivery of multiple growth factors. BMPs are well established as potent osteoinductive growth factors and their delivery in combination with other growth factors has been shown to enhance bone formation in vivo.…”

Section: Growth Factor Deliverymentioning

confidence: 99%

“…BMPs are well established as potent osteoinductive growth factors and their delivery in combination with other growth factors has been shown to enhance bone formation in vivo. 21 A study by Duneas et al demonstrated that the combination of TGF-b and BMP-7 produced a synergistic effect to enhance bone formation in vivo. 22 This synergy was also observed by Simmons et al after they implanted RGD-modified alginate hydrogels containing both TGF-b3 and BMP-2 with bone marrow stromal cells (BMSCs) in mice.…”

Section: Growth Factor Deliverymentioning

confidence: 99%

See 1 more Smart Citation

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

Nguyen

Annabi

Nikkhah³

et al. 2012

Tissue Engineering Part B: Reviews

274

236

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Section: Growth Factor Deliverymentioning

confidence: 99%

Section: Growth Factor Deliverymentioning

confidence: 99%

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

Nguyen

Annabi

Nikkhah³

et al. 2012

Tissue Engineering Part B: Reviews

274

236

View full text Add to dashboard Cite

“…1,2,[11][12][13] Growth factors are usually added to the system to strengthen MSC functionality. 14,15 Although embryonic stem (ES) cells have a much higher capacity to differentiate into many cell types, [16][17][18] there are several advantages to use MSCs rather than ES cells in addition to the ethical issues. First, ES cells have the potential to cause cancer such as teratoma, an encapsulated tumor with different organs such as hair, eye, teeth, and bone, and they are much more difficult to control in vivo than MSCs.…”

Section: Introductionmentioning

confidence: 99%

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

Chen

Crawford

Chen

et al. 2013

Tissue Engineering Part B: Reviews

206

161

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Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway. MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes, and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production, and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functionalities. Biomaterials have been modified in their properties and surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

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“…30 Given the importance of the angiogenesisosteogenesis coupling, combining the most important bioactive molecules involved in these processes can be beneficial for bone regeneration. 31 One of the major problems considering release of growth factors from delivery vehicles is the loss of biological activity. Since these growth factors have short biological half-lives, keeping the concentration of growth factor in the therapeutic window for a sufficient period of time is suggested to be important in mimicking natural bone regeneration.…”

Section: Introductionmentioning

confidence: 99%

A Differential Effect of Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor Release Timing on Osteogenesis at Ectopic and Orthotopic Sites in a Large-Animal Model

Geuze

Theyse

Kempen

et al. 2012

Tissue Engineering Part A

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In bone tissue engineering, growth factors are widely used. Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) are the most well-known regulators of osteogenesis and angiogenesis. We investigated whether the timing of dual release of VEGF and BMP-2 influences the amount of bone formation in a large-animal model. Poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) were loaded with BMP-2 or VEGF to create sustained-release profiles, and rapidly degrading gelatin was loaded with either growth factor for fast-release profiles. To study in vivo osteogenicity, the two delivery vehicles were combined with biphasic calcium phosphate (BCP) scaffolds and implanted in 10 Beagle dogs for 9 weeks, at both ectopic (paraspinal muscles) and orthotopic sites (critical-size ulnar defect). The 9 ectopic groups contained combined or single BMP/VEGF dosage, in sustained-or fast-release profiles. In the ulnae of 8 dogs, fast VEGF and sustained BMP-2 were applied to one leg, and the other received the opposite release profiles. The two remaining dogs received bilateral control scaffolds. Bone growth dynamics was analyzed by fluorochrome injection at weeks 3, 5, and 7. Postoperative and posteuthanization X-rays of the ulnar implants were taken. After 9 weeks of implantation, bone quantity and bone growth dynamics were studied by histology, histomorphometry, and fluorescence microscopy. The release of the growth factors resulted in both enhanced orthotopic and ectopic bone formation. Bone formation started before 3 weeks and continued beyond 7 weeks. The ectopic BMP-2 fast groups showed significantly more bone compared to sustained release, independent of the VEGF profile. The ulna implants revealed no significant differences in the amount of bone formed. This study shows that timing of BMP-2 release largely determines speed and amount of ectopic bone formation independent of VEGF release. Furthermore, at the orthotopic site, no significant effect on bone formation was found from a timed release of growth factors, implicating that timed-release effects are location dependent.

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Growth Factor Interactions in Bone Regeneration

Cited by 100 publications

References 175 publications

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

A Differential Effect of Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor Release Timing on Osteogenesis at Ectopic and Orthotopic Sites in a Large-Animal Model

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