Effect of rhBMP-2 and VEGF in a vascularized bone allotransplant experimental model based on surgical neoangiogenesis
Department of Orthopedics, University of São Paulo, Rua Dr Ovídio Pires de Campos, 333, Cerqueira Cesar, São Paulo, SP 05403-010, Brazil. Journal of Orthopaedic Research
(Impact Factor: 2.99).
04/2013; 31(4). DOI: 10.1002/jor.22277
We have demonstrated survival of living allogeneic bone without long-term immunosuppression using short-term immunosuppression and simultaneous creation of an autogenous neoagiogenic circulation. In this study, bone morphogenic protein-2 (rhBMP-2), and/or vascular endothelial growth factor (VEGF), were used to augment this process. Femoral diaphyseal bone was transplanted heterotopically from 46 Dark Agouti to 46 Lewis rats. Microvascular repair of the allotransplant nutrient pedicle was combined with intra-medullary implantation of an autogenous saphenous arteriovenous (AV) bundle and biodegradable microspheres containing buffer (control), rhBMP-2 or rhBMP-2 + VEGF. FK-506 given daily for 14 days maintained nutrient pedicle flow during angiogenesis. After an 18 weeks survival period, we measured angiogenesis (capillary density) from the AV bundle and cortical bone blood flow. Both measures were greater in the combined (rhBMP-2 + VEGF) group than rhBMP-2 and control groups (p < 0.05). Osteoblast counts were also higher in the rhBMP-2 + VEGF group (p < 0.05). A trend towards greater bone formation was seen in both rhBMP2 + VGF and rhBMP2 groups as compared to controls (p = 0.059). Local administration of VEGF and rhBMP-2 augments angiogenesis, osteoblastic activity and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Figures in this publication
Available from: Kuei-Chang Li
- "In this regard, co-delivery of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) synergistically facilitates segmental bone healing  . To repair massive bone defects , various tissue engineering approaches such as the use of osteoconductive scaffolds, osteoinductive growth factors and osteogenic cells have been explored alone or in combination. "
[Show abstract] [Hide abstract]
ABSTRACT: Adipose-derived stem cells (ASCs) hold promise for bone regeneration but possess inferior osteogenesis potential. Allotransplantation of ASCs engineered with the BMP2/VEGF-expressing baculoviruses into rabbits healed critical-size segmental bone defects. To translate the technology to clinical applications, we aimed to demonstrate massive bone healing in minipigs that more closely mimicked the clinical scenarios, using a new hybrid baculovirus system consisting of BacFLPo expressing the codon-optimized FLP recombinase (FLPo) and the substrate baculovirus harboring the transgene flanked by Frt sequences. Co-transduction of minipig ASCs (pASCs) with BacFLPo and the substrate baculovirus enabled transgene cassette excision, recombination and minicircle formation in ≈73.7% of pASCs, which substantially prolonged the transgene (BMP2 and VEGF) expression to 28 days. When encoding BMP2, the FLPo/Frt-based system augmented the pASCs osteogenesis. Allotransplantation of the BMP2/VEGF-expressing pASCs into minipigs healed massive segmental bone defects (30 mm in length) at the mid-diaphysis of femora, as evaluated by computed tomography, positron emission tomography, histology, immunohistochemical staining and biochemical testing. The defect size was ≈15% of femoral length in minipigs and was equivalent to ≈60-70 mm of femoral defect in humans, thus the healing using pASCs engineered with the FLPo/Frt-based baculovirus represented a remarkable advance for the treatment of massive bone defects.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Biomaterials 05/2015; 50(1). DOI:10.1016/j.biomaterials.2015.01.052 · 8.56 Impact Factor
[Show abstract] [Hide abstract]
Nowadays, open anatomic reduction and internal fixation can be considered as a valuable treatment for displaced intra-articular fractures of the calcaneus. However, the application of a calcaneal plate via an extensile lateral approach is at risk for a substantial rate of complications including delayed healing, skin necrosis, or infection. There is some evidence that a limited exposure might contribute to a decreased soft tissue complication rate bearing in mind that most minimally invasive techniques have to accept a reduced primary stability compared with the open application of an angular stable plate. Recently, an intrafocal minimal invasive reduction technique has been established employing an intramedullary nail for fracture stabilisation and support of the subtalar joint. The aim of this study was to compare the primary biomechanical performance of the new device versus lateral angular stable plating.
Material and methods:
Biomechanical testings were performed on 14 human cadaveric feet (7 pairs). Dry calcaneal bones were fractured resulting in a Sanders type IIB fracture pattern and fixed by either a calcaneal locking plate or an intramedullary calcaneal nail. Compressive testing via the corresponding talus was employed at a constant loading velocity until failure with an universal testing machine and a specific mounting device to avoid any shear forces. Apart from the data of the load deformation diagram the relative motion of the fracture elements during loading was recorded by 8 extensometric transducers. After failure the specimens were carefully examined to check the failure patterns.
The displacement of the subtalar joint fragment was substantially lower in specimens fixed with the nail. Stiffness and load to failure were significantly higher after fixation with the intramedullary nail than after application of the angular stable plate. Failure with both fixation modes generally occurred at the anterior calcaneal process fragment.
The primary stability of an intramedullary nail appeared to be superior to an angular stable plate representing the present standard technique in open reconstruction of the fractured calcaneus. The results from the experimental model speak in favour of the clinical use of the intramedullary calcaneal nail.
Injury 10/2013; 45. DOI:10.1016/j.injury.2013.10.031 · 2.14 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The treatment of large, non-healing bone defects remains a clinical challenge, and has driven efforts toward the development of new approaches to engineer vascularized bone grafts. Despite great advances in bone tissue engineering over the past decade, clinical translation of stem cell-based strategies has been limited. This article discusses the hurdles blocking the effective application of stem cell-based regeneration of mature bone with perfusable vascular networks as well as avenues for potentially overcoming those hurdles. Particular focus is placed on the combination of autologous heterogeneous cell sources with key regenerative growth factors to mimic the complex cellular and biochemical environments that occur during normal bone healing. Understanding how to guide the intrinsic self-assembly mechanisms of these cells may increase their regenerative efficacy and enable in situ tissue morphogenesis. The development of more effective, safer, and simpler approaches to engineer vascularized bone grafts may bring stem cell-based approaches closer to wider clinical application.
Current Opinion in Chemical Engineering 02/2014; 3:75–82. DOI:10.1016/j.coche.2013.12.002
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.