Role of Growth Factors in the Incorporation of Unloaded Bone Allografts in the Goat

Lamerigts, N.M.P.; Buma, P.; Aspenberg, Per; Schreurs, B.W.; Slooff, T. J. J. H.

doi:10.1097/00003086-199911000-00032

Cited by 24 publications

(11 citation statements)

References 49 publications

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“…FGF‐2 has proven to be a variably effective osteogenic cytokine in frozen allografts 16, 37, 38. Lamerigts et al described an angiogenic effect of FGF‐2 in frozen bone allografts as well that we were unable to confirm, seeing only a nonsignificant trend towards higher bone blood flow and increased bone turnover.…”

Section: Discussioncontrasting

confidence: 65%

Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF‐2 and VEGF

Willems

Larsen

Giusti

et al. 2011

Journal Orthopaedic Research

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Frozen bone allografts are susceptible to nonunion and fracture due to limited revascularization and incomplete bone remodeling. We aim to revascularize bone allografts by combining angiogenesis from implanted arteriovenous (AV) bundles with delivery of fibroblast growth factor (FGF-2) and/or vascular endothelial growth factor (VEGF) via biodegradable microspheres. Rat femoral diaphyseal allografts were frozen at À808C, and heterotopically transplanted over a major histocompatibility mismatch. A saphenous AV bundle was inserted into the intramedullary canal. Growth factor was encapsulated into microspheres and inserted into the graft, providing localized and sustained drug release. Forty rats were included in four groups: (I) phosphate-buffered saline, (II) FGF-2, (III) VEGF, and (IV) FGF-2 þ VEGF. At 4 weeks, angiogenesis was measured by the hydrogen washout method and microangiography. Bone remodeling was evaluated by quantitative histomorphometry and histology. Bone blood flow was significantly higher in groups III and IV compared to control (p < 0.05). Similarly, bone remodeling was higher in VEGF groups. FGF-2 had little effect on allograft revascularization. No synergistic effect was observed with use of both cytokines. Delivered in microspheres, VEGF proved to be a potent angiogenic cytokine, increasing cortical bone blood flow and new bone formation in frozen allografts revascularized with an implanted AV bundle.

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Section: Discussioncontrasting

confidence: 65%

Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF‐2 and VEGF

Willems

Larsen

Giusti

et al. 2011

Journal Orthopaedic Research

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“…Indeed, the alpha granules of platelets, releasing several growth factors in the fracture rim, such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-b), fibroblast growth factor (FGF-b), and vascular endothelial growth factor (VEGF) stimulate polymorphonuclear leukocytes, lymphocytes, monocytes, and macrophages [69]. TGF-b and PDGF molecules show in vivo osteoinductive capacity [70, 71]. Moreover, VEGF enhances bone formation and bone healing by improving angiogenesis [72], and appears to be an appropriate tool to induce bone healing in atrophic non-unions [73].…”

Section: Discussionmentioning

confidence: 99%

Tissue Engineered Strategies for Pseudoarthrosis

Longo¹,

Trovato²,

Loppini³

et al. 2012

TOORTHJ

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Numerous classification systems of non-union have been proposed based on: presence or absence of infection, radiographic features, clinical findings, biologic activity, location and shape. The management of pseudarthrosis is strongly related to the type of non-union (infected versus uninfected, atrophic versus hypertrophic). Surgical management of pseudarthrosis is generally effective with a success rate ranging from 75 to 100%. Nevertheless, in a relatively high number of instances several combined treatments are required for the fracture healing. The current gold standard to stimulate the bone regeneration is represented by the revision surgery with the application of autologous bone grafts. However, several approaches have been described to promote and enhance the bone tissue regeneration, including extracorporeal shock wave therapy (ESWT), ultrasound, electromagnetic, bone morphogenic proteins (BMPs) and platelet-rich-plasma (PRP).The aim of the present study was to perform a systematic review of the literature evaluating the current therapies to promote and enhance the bone tissue healing. The systematic review was performed according to PRISMA guidelines with a PRISMA checklist and algorithm.Limitations of the present systematic review are mainly related to the scanty quality of the studies available in the literature. Although the therapies previously described for the management of patients with non-unions seems to be effective, the limitations of the included studies, especially the extensive clinical heterogeneity, make not possible to provide clear recommendations regarding the application of these approaches. The problems remain the need to better understand the most effective treatment options, subject to surgical stabilization as a first step.

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“…There are several explanations for the observed lack of stimulatory effects of OP‐1. Certainly, the potency of BMPs in general to induce bone directly by intra‐membranous or enchondral ossification is well known for many years 26, 33–35. The mechanism of bone formation may be related to the location, the presence and differentiation status of progenitor cells, and the local loading conditions 35.…”

Section: Discussionmentioning

confidence: 99%

No effect of bone morphogenetic protein‐7 (OP‐1) on the incorporation of impacted bone grafts in a realistic acetabular model

Buma¹,

Arts²,

Gardeniers³

et al. 2007

J Biomed Mater Res

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Bone morphogenetic proteins (BMPs) accelerate bone repair in experimental and clinical conditions. Impacted Morsellized Cancellous Bone grafts (MCB) are successfully used to reconstruct bone defects after failed hip implants. The main question in this study was if BMP-7 (OP-1) mixed with MCB could accelerate the incorporation of MCB and prevents the formation of a soft tissue interface after remodeling of the MCB. A large loaded defect in the acetabulum of goats was reconstructed with a wire mesh and with MCB or MCB mixed with OP-1. After 6 weeks, no differences were found in the revascularization process, in the number of osteoclasts resorbing the MCB, and in the thickness and appearance of the fibrous interface between MCB with or without OP-1. After 6 weeks, enchondral bone had formed in the bone graft layer and on the periosteal anterior and superior rim in the OP-1 group only. More periosteal bone and more bone in the holes of the mesh had been formed in most OP-1 goats. Most MCB was replaced by new lamellar bone after 15 weeks in both groups. We speculate that during or directly after impaction most of the OP-1 is released from the carrier inducing an early effect outside the reconstructive layer at the periosteal side of the acetabulum. Probably most OP-1 has left the reconstruction by the time new vessels and progenitors reached the bone graft. These results do not support the use of OP-1 in impaction bone grafting in patients.

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Role of Growth Factors in the Incorporation of Unloaded Bone Allografts in the Goat

Cited by 24 publications

References 49 publications

Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF‐2 and VEGF

Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF‐2 and VEGF

Tissue Engineered Strategies for Pseudoarthrosis

No effect of bone morphogenetic protein‐7 (OP‐1) on the incorporation of impacted bone grafts in a realistic acetabular model

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