rhBMP-2 Enhances the Bone Healing Response in a Diabetic Rat Segmental Defect Model

Azad, Vikrant; Breitbart, Eric A.; Al-Zube, Loay; Yeh, Sloane; O’Connor, J. P.; Lin, Sheldon S.

doi:10.1097/bot.0b013e31819f290e

Cited by 45 publications

(41 citation statements)

References 49 publications

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“…First, in contrast to collagen foams [51], GFOGER-functionalized materials enhance bone formation without cell or protein co-delivery due to the intrinsic osteogenic bioactivity of the α2β1 integrin-specific GFOGER peptide. Simple presentation of GFOGER within the hydrogel significantly enhanced bone formation, outperforming other adhesive peptides such as RGD.…”

Section: Discussionmentioning

confidence: 99%

Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle

Shekaran¹,

García²,

Clark³

et al. 2014

Biomaterials

162

144

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Non-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle. GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell differentiation and produced significant enhancements in bone repair within a critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER functionalization was crucial to the BMP-2-dependent healing response. Importantly, these engineered hydrogels outperformed the current clinical carrier in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels provided sustained in vivo release of encapsulated BMP-2, increased osteoprogenitor localization in the defect site, enhanced bone formation and induced defect bridging and mechanically robust healing at low BMP-2 doses which stimulated almost no bone regeneration when delivered from collagen sponges. These findings demonstrate that GFOGER hydrogels promote bone regeneration in challenging defects with low delivered BMP-2 doses and represent an effective delivery vehicle for protein therapeutics with translational potential.

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Section: Discussionmentioning

confidence: 99%

Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle

Shekaran¹,

García²,

Clark³

et al. 2014

Biomaterials

162

144

View full text Add to dashboard Cite

show abstract

“…83 Furthermore, PRP treatment improved the mechanical strength of the diabetic rat fracture calluses. A recent study by Azad et al 84 reported that recombinant human bone morphogenetic protein-2 (rhBMP-2) enhanced bone formation radiographically and histologically in spontaneously diabetic BB Wistar rats, possibly through an increase in angiogenesis. Mechanically, fracture calluses from diabetic rats treated with rhBMP-2 showed better torque to failure and torsional rigidity values.…”

Section: Current Treatment Influence On Bone and Cartilage Formationmentioning

confidence: 97%

“…Mechanically, fracture calluses from diabetic rats treated with rhBMP-2 showed better torque to failure and torsional rigidity values. 84 Plateletderived growth factor was also one of the factors investigated in early diabetic fracture callus compared with that of healthy controls. 85 It has been reported that PDGF was decreased at the mRNA level and protein levels in spontaneously diabetic animals.…”

Section: Current Treatment Influence On Bone and Cartilage Formationmentioning

confidence: 99%

Impact of Diabetes on Fracture Healing

Graves

Alblowi

Paglia³

et al. 2011

Journal of Experimental & Clinical Medicine

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“…One such development is the current clinical use of locally applied recombinant proteins that include bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2) for promoting osteogenesis. There have been a few studies that have explored the effect of locally applied recombinant human BMP-2 and FGF-2 to achieve bone regeneration in DM [14, 15] and non-DM bone defect models [16-18]. It has been shown that BMP-2 treatment of fractures in a diabetic setting increased callus formation, vascularity and mechanical properties [14].…”

Section: Introductionmentioning

confidence: 99%

Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model

Khorsand

Nicholson

et al. 2017

Journal of Controlled Release

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Bone fracture healing impairment related to systemic diseases such as diabetes can be addressed by growth factor augmentation. We previously reported that growth factors such as fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) work synergistically to encourage osteogenesis in vitro. In this report, we investigated if BMP-2 and FGF-2 together can synergistically promote bone repair in a leporine model of diabetes mellitus, a condition that is known to be detrimental to union. We utilized two kinds of plasmid DNA encoding either BMP-2 or FGF-2 formulated into polyethylenimine (PEI) complexes. The fabricated nanoplexes were assessed for their size, charge, in vitro cytotoxicity, and capacity to transfect human bone marrow stromal cells (BMSCs). Using diaphyseal long bone radial defects in a diabetic rabbit model it was demonstrated that co-delivery of PEI-(pBMP-2+pFGF-2) embedded in collagen scaffolds resulted in a significant improvement in bone regeneration compared to PEI-pBMP-2 embedded in collagen scaffolds alone. This study demonstrated that scaffolds loaded with PEI-(pBMP-2+pFGF-2) could be an effective way of promoting bone regeneration in patients with diabetes.

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rhBMP-2 Enhances the Bone Healing Response in a Diabetic Rat Segmental Defect Model

Abstract: Clearly, although DM has a known impact on osseous healing, its negative effects are ameliorated with the application of the rhBMP-2-collagen carrier and demonstrates the potential clinical role of this adjunct in the clinical arena.

Cited by 45 publications

References 49 publications

Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle

Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle

Impact of Diabetes on Fracture Healing

Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model

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