The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Joel D Boerckel - One of the best experts on this subject based on the ideXlab platform.
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effects of bmp 2 on neovascularization during large Bone Defect regeneration
Tissue Engineering Part A, 2019Co-Authors: Hope B Pearson, Devon E Mason, Christopher D Kegelman, Liming Zhao, James H Dawahare, Melissa A Kacena, Joel D BoerckelAbstract:Abstract Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large Bone Defect repair. Recombinant BMP-2 delivery induces robust Bone formation and has been observed to enhance neovascularization, but whether the angiogenic effects of BMP-2 are due to direct endothelial cell stimulation or to indirect paracrine signaling remains unclear. Here, we evaluated the effects of BMP-2 delivery on vascularized Bone regeneration and tested whether BMP-2 induces neovascularization directly or indirectly. We found that delivery of BMP-2 (5 μg) enhanced both Bone formation and neovascularization in critically sized (8 mm) rat femoral Bone Defects; however, BMP-2 did not directly stimulate angiogenesis in vitro. In contrast, conditioned medium from both mesenchymal progenitor cells and osteoblasts induced angiogenesis in vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, co-delivery of BMP-2 with endothelial colony forming cells (ECFCs) to a heterotopic site, distant from the Bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that BMP-2 induces neovascularization during Bone regeneration primarily through paracrine activation of osteoprogenitor cells.
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effects of Bone morphogenetic protein 2 on neovascularization during large Bone Defect regeneration
Tissue Engineering Part A, 2019Co-Authors: Hope B Pearson, Joel D Boerckel, Devon E Mason, Christopher D Kegelman, Liming Zhao, James H Dawahare, Melissa A KacenaAbstract:Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large Bone Defect repair. Recombinant Bone morphogenetic protein-2 (BMP-2) delivery induces robust Bone ...
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recovery from hind limb ischemia enhances rhbmp 2 mediated segmental Bone Defect repair in a rat composite injury model
Bone, 2013Co-Authors: Brent A Uhrig, Joel D Boerckel, Montzu A Li, Nick J. Willett, Nathaniel Huebsch, Robert E. GuldbergAbstract:article Although severe extremity trauma is often inclusive of skeletal and vascular damage in combination, segmen- tal Bone Defect repair with concomitant vascular injury has yet to be experimentally investigated. To this end, we developed a novel rat composite limb injury model by combining a critically-sized segmental Bone Defect with surgically-induced hind limb ischemia (HLI). Unilateral 8 mm femoral Defects were created alone (BD) or in combination with HLI (BD + HLI), and all Defects were treated with rhBMP-2 via a hybrid biomaterial delivery system. Based on reported clinical and experimental observations on the importance of vascular net- works in Bone repair, we hypothesized that HLI would impair Bone regeneration. Interestingly, the BD + HLI group displayed improved radiographic bridging, and quantitative micro-CT analysis revealed enhanced Bone regeneration as early as week 4 (p b 0.01) that was sustained through week 12 (p b 0.001) and confirmed histologically. This effect was observed in two independent studies and at two different doses of rhBMP-2. Micro-CT angiography was used to quantitatively evaluate vascular networks at week 12 in both the thigh and the regenerated Bone Defect. No differences were found between groups in total blood vessel volume in the thigh, but clear differences in morphology were present as the BD + HLI group possessed a more interconnected network of smaller diameter vessels (p b 0.001). Accordingly, while the overall thigh vessel volume was comparable between groups, the contributions to vessel volume based on vessel diameter dif- fered significantly. Despite this evidence of a robust neovascular response in the thigh of the BD + HLI group, differences were not observed between groups for Bone Defect blood vessel volume or morphology. In total, our results demonstrate that a transient ischemic insult and the subsequent recovery response to HLI significantly enhanced BMP-2-mediated segmental Bone Defect repair, providing additional complexity to the relationship between vascular tissue networks and Bone healing. Ultimately, a better understanding of the coupling mechanisms may reveal important new strategies for promoting Bone healing in challenging clinical scenarios.
Michael Mork Petersen - One of the best experts on this subject based on the ideXlab platform.
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in vivo gentamicin concentrations in plasma and drain fluid after Bone Defect reconstruction using a gentamicin eluting Bone graft substitute
Orthopaedic Proceedings, 2018Co-Authors: Peter Frederik Horstmann, W Hettwer, Z Song, Michael Mork PetersenAbstract:To document early in-vivo concentrations of gentamicin in plasma and drain fluid after Bone Defect reconstruction using a gentamicin-eluting Bone graft substitute.IntroductionReconstruction of Bone Defects after surgical Bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting Bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications.We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent Bone Defect reconstruction with a gentamicin-eluting Bone graft substitute (CERAMENT™|G – BoneSUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic Bone disease (n=3, proximal humerus), giant cell...
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in vivo gentamicin concentrations in plasma and drain fluid after Bone Defect reconstruction using a gentamicin eluting Bone graft substitute
Journal of Bone and Joint Surgery-british Volume, 2015Co-Authors: Peter Frederik Horstmann, W Hettwer, Z Song, Michael Mork PetersenAbstract:To document early in-vivo concentrations of gentamicin in plasma and drain fluid after Bone Defect reconstruction using a gentamicin-eluting Bone graft substitute. Introduction Reconstruction of Bone Defects after surgical Bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting Bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent Bone Defect reconstruction with a gentamicin-eluting Bone graft substitute (CERAMENT™|G – BoneSUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic Bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting Bone graft substitute was used, either alone or in combination with cancellous allograft and/or a Bone graft substitute not containing gentamicin (CERAMENT™|BVF – BoneSUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting Bone graft substitute for Bone Defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations.
Peter Frederik Horstmann - One of the best experts on this subject based on the ideXlab platform.
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in vivo gentamicin concentrations in plasma and drain fluid after Bone Defect reconstruction using a gentamicin eluting Bone graft substitute
Orthopaedic Proceedings, 2018Co-Authors: Peter Frederik Horstmann, W Hettwer, Z Song, Michael Mork PetersenAbstract:To document early in-vivo concentrations of gentamicin in plasma and drain fluid after Bone Defect reconstruction using a gentamicin-eluting Bone graft substitute.IntroductionReconstruction of Bone Defects after surgical Bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting Bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications.We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent Bone Defect reconstruction with a gentamicin-eluting Bone graft substitute (CERAMENT™|G – BoneSUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic Bone disease (n=3, proximal humerus), giant cell...
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in vivo gentamicin concentrations in plasma and drain fluid after Bone Defect reconstruction using a gentamicin eluting Bone graft substitute
Journal of Bone and Joint Surgery-british Volume, 2015Co-Authors: Peter Frederik Horstmann, W Hettwer, Z Song, Michael Mork PetersenAbstract:To document early in-vivo concentrations of gentamicin in plasma and drain fluid after Bone Defect reconstruction using a gentamicin-eluting Bone graft substitute. Introduction Reconstruction of Bone Defects after surgical Bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting Bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent Bone Defect reconstruction with a gentamicin-eluting Bone graft substitute (CERAMENT™|G – BoneSUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic Bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting Bone graft substitute was used, either alone or in combination with cancellous allograft and/or a Bone graft substitute not containing gentamicin (CERAMENT™|BVF – BoneSUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting Bone graft substitute for Bone Defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations.
Xin Luan Wang - One of the best experts on this subject based on the ideXlab platform.
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osteogenic magnesium incorporated into plga tcp porous scaffold by 3d printing for repairing challenging Bone Defect
Biomaterials, 2019Co-Authors: Yu Xiao Lai, Xin Luan Wang, David Eglin, Tingting Tang, Jiang Peng, Huijuan Cao, Jing Long, Qingyun Jia, Bin Teng, Mauro AliniAbstract:Bone Defect repair is a challenging clinical problem in musculoskeletal system, especially in orthopaedic disorders such as steroid associated osteonecrosis (SAON). Magnesium (Mg) as a biodegradable metal with properly mechanical properties has been investigating for a long history. In this study, Mg powder, poly (lactide-co-glycolide) (PLGA), β-tricalcium phosphate (β-TCP) were the elements to formulate a novel porous PLGA/TCP/Mg (PTM) scaffolds using low temperature rapid prototyping (LT-RP) technology. The physical characterization of PTM scaffold and Mg ions release were analyzed in vitro. The osteogenic and angiogenic properties of PTM scaffolds, as well as the biosafety after implantation were assessed in an established SAON rabbit model. Our results showed that the PTM scaffold possessed well-designed bio-mimic structure and improved mechanical properties. Findings of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and micro-computed tomography (micro CT)-based angiography indicated that PTM scaffold could increase blood perfusion and promote new vessel ingrowth at 4 weeks after surgery, meanwhile, a plenty of newly formed vessels with well-architective structure were observed at 8 weeks. Correspondingly, at 12 weeks after surgery, micro-CT, histological and mechanical properties analysis showed that PTM could significant enhance new Bone formation and strengthen newly formed Bone mechanical properties. The mean Bone volume in PTM group was 56.3% greater than that in PT group. Biosafety assessments from 0 to 12 weeks after implantation did not induce increase in serum Mg ions concentration, and immune response, liver and kidney function parameters were all at normal level. These findings suggested that the PTM scaffold had both osteogenic and angiogenic abilities which were synergistic effect in enhancing new Bone formation and strengthen newly formed Bone quality in SAON. In summary, PTM scaffolds are promising composite biomaterials for repairing challenging Bone Defect that would have great potential for its clinical translation.
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Bone Defect animal models for testing efficacy of Bone substitute biomaterials
Journal of Orthopaedic Translation, 2015Co-Authors: Ye Li, Shu Kui Chen, Xin Luan Wang, Ling Qin, Long Li, Yu Xiao LaiAbstract:Large Bone Defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing Bone Defects with biomaterials developed as a Defect filler, which can promote Bone regeneration, is essential. In order to evaluate biomaterials to be developed as Bone substitutes for Bone Defect repair, it is essential to establish clinically relevant invitro and invivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the invitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the invivo tests constitute a step midway between invitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable invivo Bone Defect animal model for testing Bone substitutes for Defect repair. This review aimed at introducing and discussing the most available and commonly used Bone Defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical Bone Defect models with various animal species and the evaluation methodologies of the Bone regeneration process after the implantation of Bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.
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plga tcp composite scaffold incorporating bioactive phytomolecule icaritin for enhancement of Bone Defect repair in rabbits
Acta Biomaterialia, 2013Co-Authors: S H Chen, Xin Luan Wang, Xinhui Xie, Ming Lei, Lizhen Zheng, Dong Yao, Zhihe Zhao, A KongAbstract:Bone Defect repair is challenging in orthopaedic clinics. For treatment of large Bone Defects, Bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides support to enhance biological Bone repair. As therapeutic agents are desirable for enhancing Bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12 mm ulnar Bone Defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed Bone within Bone Defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized Bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.
Devon E Mason - One of the best experts on this subject based on the ideXlab platform.
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effects of bmp 2 on neovascularization during large Bone Defect regeneration
Tissue Engineering Part A, 2019Co-Authors: Hope B Pearson, Devon E Mason, Christopher D Kegelman, Liming Zhao, James H Dawahare, Melissa A Kacena, Joel D BoerckelAbstract:Abstract Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large Bone Defect repair. Recombinant BMP-2 delivery induces robust Bone formation and has been observed to enhance neovascularization, but whether the angiogenic effects of BMP-2 are due to direct endothelial cell stimulation or to indirect paracrine signaling remains unclear. Here, we evaluated the effects of BMP-2 delivery on vascularized Bone regeneration and tested whether BMP-2 induces neovascularization directly or indirectly. We found that delivery of BMP-2 (5 μg) enhanced both Bone formation and neovascularization in critically sized (8 mm) rat femoral Bone Defects; however, BMP-2 did not directly stimulate angiogenesis in vitro. In contrast, conditioned medium from both mesenchymal progenitor cells and osteoblasts induced angiogenesis in vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, co-delivery of BMP-2 with endothelial colony forming cells (ECFCs) to a heterotopic site, distant from the Bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that BMP-2 induces neovascularization during Bone regeneration primarily through paracrine activation of osteoprogenitor cells.
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effects of Bone morphogenetic protein 2 on neovascularization during large Bone Defect regeneration
Tissue Engineering Part A, 2019Co-Authors: Hope B Pearson, Joel D Boerckel, Devon E Mason, Christopher D Kegelman, Liming Zhao, James H Dawahare, Melissa A KacenaAbstract:Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large Bone Defect repair. Recombinant Bone morphogenetic protein-2 (BMP-2) delivery induces robust Bone ...