RHBMP-2 Delivered in a Calcium Phosphate Cement Accelerates Bridging of Critical-Sized Defects in Rabbit Radii

Seeherman, Howard; Azari, Kodi; Bidic, Sean M.; Rogers, Leif; LI, X. JIAN; Hollinger, Jeffrey O.; Wozney, John M.

doi:10.2106/00004623-200607000-00017

Cited by 32 publications

(33 citation statements)

References 53 publications

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“…Variants of the BMP-2 genes are associated with familial osteoporosis, and rhBMP-2 can reverse bone loss in osteopenic mice [31,32]. Controlled release of rhBMP-2 can be obtained easily when the protein is mixed with CPC during cement setting, and rhBMP-2/CPC is effective in bridging critical-sized bone defects without osteoporosis [4,11,28]. Therefore, rhBMP-2 was chosen to enhance osteoinduction of CPC in our research.…”

Section: Discussionmentioning

confidence: 99%

“…rhBMP-2 is widely used to enhance osteoinduction of bone substitutes [8,11,17,25,28,29]. In several studies rhBMP-2/carrier formulations were associated with bridging of critical-sized bone defects [11,28,29], but rhBMP-2/CPC was the only combination to restore torsional mechanical properties equivalent to those of normal bone [29].…”

Section: Introductionmentioning

confidence: 99%

“…In several studies rhBMP-2/carrier formulations were associated with bridging of critical-sized bone defects [11,28,29], but rhBMP-2/CPC was the only combination to restore torsional mechanical properties equivalent to those of normal bone [29]. The weakness of rhBMP-2/CPC is the slow release One or more of the authors (ML, XL) have received funding from a research grant at the Chinese People's Liberation Army (Grant Number of 06MA090) and a grant of Gansu Natural Science Foundation (Grant Number of 0710RJZA068).…”

Section: Introductionmentioning

confidence: 99%

“…Li, X. Liu (&), X. Liu, B. Ge Orthopedic Trauma Institute of CPLA, Lanzhou General Hospital of CPLA, 333 Bing-he-nan Road, Lanzhou 730050 Gansu Province, People's Republic of China e-mail: xingyanliulz@yahoo.com.cn rate of the factor and the long degradation period [4,28]. Poly[D,L-lactic-co-glycolic] acid (PLGA) microspheres loaded with rhBMP-2 and incorporated into CPC [4,24,25] may provide an alternative bone substitute.…”

Section: Introductionmentioning

confidence: 99%

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Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Liu

et al. 2010

Clinical Orthopaedics &Amp; Related Research

108

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Background The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis. Questions/purposes We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing. Methods We soaked rhBMP-2/GM/CPC and rhBMP-2/ CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology). Results The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/ CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation. Conclusions The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects. Clinical Relevance These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Liu

et al. 2010

Clinical Orthopaedics &Amp; Related Research

108

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“…The usefulness of this technique is still under intense study by several investigators using different animal models [4,67,77,95,97,100]. Simple injection of osteoinductive growth factors in subcutaneous tissue has showed that it can promote bone formation [97,100].…”

Section: Injection Of Growth Factors For Enhancement Of Fracture Healingmentioning

confidence: 99%

Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today

Pountos

Georgouli

Kontakis

et al. 2009

International Orthopaedics (SICOT)

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The successful treatment of nonunions represents a major challenge for orthopaedic surgeons. Lately, ongoing advances made in the field of molecular medicine and molecular biology have increased our understanding of the pathways and involvement of mediators surrounding the bone healing process. As a result, the surgeon's armamentarium has been increased in terms of options for intervention. This article aims to provide an overview of minimally invasive techniques applicable in the treatment of nonunions of fractures.

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Biological activity of recombinant human growth factors released from biocompatible bone implants

Ziegler

Anger

Krummenauer

et al. 2007

J Biomedical Materials Res

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The present investigation was performed to study the bioactivity of osteoinductive and osteoproliferative growth factors after release from biocompatible bone implants. Three types of porous carriers were used in this study: hydroxyapatite, alpha tricalcium phosphate, and a neutralized glass ceramic. Implants were loaded with recombinant human bone morphogenetic protein 2 (rh-BMP-2) and recombinant human basic fibroblast growth factor (rh-bFGF) in a concentration of 2 microg/150 microL PBS each. The released growth factors were then applicated into SAOS-2-cell cultures. After 3, 5, and 7 days cell differentiation was measured by the activity of alkaline phosphatase (ALP), cell proliferation by using a MTT assay as well as a cell counter. Rh-BMP-2 released during the first hour from the scaffolds led to a significant increase of the activity of ALP in the incubated SAOS-2-cell culture after 3, 5, and 7 days. However, the incubation with rh-BMP-2 released after 24 h was not found to increase the expression of ALP. The incubation of cell cultures with rh-bFGF released during the first hour led to a significant increase of cell number and of extinction in the MTT assay, whereas this increase was not observed after incubation with rh-bFGF released after 24 h. The in vitro measured biological activity of released growth factors from the surface of synthetic implants is time-depending. If prolonged osteoinductive and osteoproliferative potency of growth factors is desired, a modified application technique should be chosen to stabilize those proteins.

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RHBMP-2 Delivered in a Calcium Phosphate Cement Accelerates Bridging of Critical-Sized Defects in Rabbit Radii

Cited by 32 publications

References 53 publications

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today

Biological activity of recombinant human growth factors released from biocompatible bone implants

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