Complications with the Use of BMP-2 in Scaphoid Nonunion Surgery

Brannan, Patrick; Gaston, Glenn; Lewis, Dan D.; Loeffler, Bryan J.

doi:10.1016/j.jhsa.2015.06.024

Cited by 6 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RhBMP‐2 is the most potent osteoinductive agent available today; however, rhBMP‐2 has not fulfilled its clinical promise. First, when loaded on a collagen sponge, large doses of protein are needed to have an adequate biologic, and the use of supraphysiologic doses of rhBMP‐2 has led to questions about its clinical safety, and some clinical studies have demonstrated complications such as soft tissue edema, heterotopic ossification, and cyst formation associated with rhBMP‐2 use …”

Section: Discussionmentioning

confidence: 99%

“…First, when loaded on a collagen sponge, large doses of protein are needed to have an adequate biologic, 8,34 and the use of supraphysiologic doses of rhBMP-2 has led to questions about its clinical safety, and some clinical studies have demonstrated complications such as soft tissue edema, heterotopic ossification, and cyst formation associated with rhBMP-2 use. 35,36 Ex vivo regional gene therapy using a LV containing the cDNA for BMP-2 is a promising strategy that allows for sustained release of BMP-2 over several months, thus offering an advantage over recombinant proteins. 29 Prior studies from our lab have used traditionally fabricated demineralized bone matrix, collagen sponge, and ceramic composites as scaffolds to deliver transduced cells to critical-sized bone defects.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

Alluri

Jakus

Bougioukli

et al. 2018

J Biomedical Materials Res

View full text Add to dashboard Cite

The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold. In vitro BMP-2 production was assessed using enzyme-linked immunosorbent assay analysis. The ability of ADSCs loaded on the HB scaffold to induce in vivo bone formation in a hind limb muscle pouch model was assessed in the following groups: ADSCs transduced with LV-BMP-2, LV-green fluorescent protein, ADSCs alone, and empty HB scaffolds. Bone formation was assessed using radiographs, histology and histomorphometry. Transduced ADSCs BMP-2 production on the HB scaffold at 24 hours was similar on 3D printed HB scaffolds versus control wells with transduced cells alone, and continued to increase after 1 and 2 weeks of culture. Bone formation was noted in LV-BMP-2 animals on plain radiographs at 2 and 4 weeks after implantation; no bone formation was noted in the other groups. Histology demonstrated that the LV-BMP-2 group was the only group that formed woven bone and the mean bone area/tissue area was significantly greater when compared with the other groups. 3D printed HB scaffolds are effective carriers for transduced ADSCs to promote bone repair. The combination of gene therapy and tissue engineered scaffolds is a promising multidisciplinary approach to bone repair with significant clinical potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1104-1110, 2018.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

Alluri

Jakus

Bougioukli

et al. 2018

J Biomedical Materials Res

View full text Add to dashboard Cite

show abstract

“…BMP‐7 is currently used in experimental studies to increase bone formation . It has been reported that BMPs induce heterotopic ossification and therefore BMP‐7 is one of the best reagents for establishing a positive control …”

Section: Introductionmentioning

confidence: 99%

CD34⁺ cells seeded in collagen scaffolds promote bone formation in a mouse calvarial defect model

et al. 2017

View full text Add to dashboard Cite

Bone tissue engineering (BTE) holds promise for managing the clinical problem of large bone defects. However, clinical adoption of BTE is limited due to limited vascularization of constructs, which could be circumvented by pre-cultivation of osteogenic and endothelial derived cells in natural-based polymer scaffolds. However, until now not many studies compared the effect of mono- and cocultures pre-seeded in collagen before implantation. We utilized a mouse calvarial defect model and compared five groups of collagen scaffolds: a negative control of a collagen scaffold alone, a positive control treated with BMP-7, monocultures of either human osteoblasts (hOBs) or CD34+ cells, and a coculture of hOB and CD34 cells. Each pre-seeded collagen scaffold was implanted in mice. After 6 weeks mice were sacrificed and their skulls prepared for volumetric and histologic analysis. We found that a monoculture of CD34 cells and a coculture of hOB and CD34 cells pre-cultured in the collagen scaffold increased bone regeneration to a similar extend. In these groups, greater amounts of new bone were found compared with hOB monocultures. Interestingly, monoculture of CD34 cells demonstrated better fracture healing than monoculture of hOBs, emphasizing the possible role of angiogenesis. Our results are promising regarding a cellular based collagen BTE construct, but more work is needed to understand the complex interaction between the osteogenic and endothelial cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1505-1516, 2018.

show abstract

“…Elucidation of novel strategies to promote reparative osteogenesis is critical and may potentially benefit large numbers of patients. Recombinant bone morphogenetic protein (BMP) 2, BMP 7, and teriparatide have been developed for clinical use as therapeutics that target inherent bone anabolic pathways, but each has disadvantages that have limited their widespread use …”

mentioning

confidence: 99%

“…Recombinant bone morphogenetic protein (BMP) 2, BMP 7, and teriparatide have been developed for clinical use as therapeutics that target inherent bone anabolic pathways, but each has disadvantages that have limited their widespread use. [4][5][6] The hedgehog (Hh) signaling pathway is critical to developmental osteogenesis 7,8 and bone homeostasis. 9 Hh ligands activate signaling through one pathway consisting of two transmembrane receptors: Patched1 (Ptch1) and Smoothened (Smo).…”

mentioning

confidence: 99%

Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice

McKenzie

Maschhoff

Liu

et al. 2018

Journal Orthopaedic Research

View full text Add to dashboard Cite

Fracture healing is a complex process of many coordinated biological pathways. This system can go awry resulting in nonunion, which leads to significant patient morbidity. The Hedgehog (Hh) signaling pathway is upregulated in fracture healing. We hypothesized that the Hh signaling pathway can be pharmacologically modulated to positively affect fracture healing. Diaphyseal femur fractures were created in elderly mice (18 months, C57BL/6 females), which have a blunted and delayed healing response compared to younger mice, and were stabilized with intramedullary pins. To activate the Hh pathway we targeted the receptor Smoothened using an agonist (Hh-Ag1.5 [Hh-Ag]) and compared this to a vehicle control. Expression of Hh target genes were significantly increased in the fracture callus of the agonist group compared to controls, indicating pathway activation. Expression of osteogenic and chondrogenic-related genes was greatly upregulated in fracture callus vs. intact femora, although Hh agonist treatment did not consistently enhance this response. Blindly graded, radiographic callus healing scores were significantly higher in the Hh-Ag groups at post operative day (POD) 14, indicating earlier callus bridging. On microCT, Hh-Ag treatment led to greater callus volume (+40%) and bone volume (+25%) at POD21. By day 14, callus vascularity, as assessed by 3D microCT angiography vessel volume, was 85% greater in the Hh-Ag group. Finally, mechanical strength of the calluses in the Hh-Ag groups was significantly greater than in the control groups at POD21. In conclusion, systemic administration of a Hh agonist appears to improve the osseous and vascular healing responses in a mouse fracture healing-impaired model.

show abstract

Complications with the Use of BMP-2 in Scaphoid Nonunion Surgery

Cited by 6 publications

References 0 publications

3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

CD34⁺ cells seeded in collagen scaffolds promote bone formation in a mouse calvarial defect model

Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice

Contact Info

Product

Resources

About

Complications with the Use of BMP-2 in Scaphoid Nonunion Surgery

Cited by 6 publications

References 0 publications

3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

3D printed hyperelastic “bone” scaffolds and regional gene therapy: A novel approach to bone healing

CD34+ cells seeded in collagen scaffolds promote bone formation in a mouse calvarial defect model

Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice

Contact Info

Product

Resources

About

CD34⁺ cells seeded in collagen scaffolds promote bone formation in a mouse calvarial defect model