Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix

Ben-David, Dror; Srouji, Samer; Shapira-Schweitzer, Keren; Kossover, Olga; Ivanir, Eran; Kuhn, Gisela; Müller, Ralph; Seliktar, Dror; Livne, Erella

doi:10.1016/j.biomaterials.2013.01.035

Cited by 98 publications

(93 citation statements)

References 43 publications

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“…2 Among the various direct osteogenic GFs, bone morphogenic protein-2 (BMP-2) is believed to be the most potent and has received clinical clearance from the US Food and Drug Administration. [7][8][9] However, a large dose of BMP-2 is necessary for an effective therapeutic effect because BMP-2 stimulates osteoregeneration only at a high concentration, 10,11 and its half-life is as short as 7 minutes in vivo. 11,12 This large dose results in high costs and adverse effects, including inflammation, swelling, ectopic bone formation, and even carcinogenicity.…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] However, a large dose of BMP-2 is necessary for an effective therapeutic effect because BMP-2 stimulates osteoregeneration only at a high concentration, 10,11 and its half-life is as short as 7 minutes in vivo. 11,12 This large dose results in high costs and adverse effects, including inflammation, swelling, ectopic bone formation, and even carcinogenicity. 13 One feasible method to overcome these drawbacks is the selection of alternative GFs that enhance osteoregeneration at lower doses; another is the development of a GF delivery system that finds the ideal balance between releasing the GF at a minimal concentration and delivering it over a sufficiently long duration.…”

Section: Introductionmentioning

confidence: 99%

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Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Liu

Deng

Sun

et al. 2016

IJN

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Objective To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods Three groups of PlGF-2/BMP-2-loaded heparin– N -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 μg PlGF-2; with 1.0 μg BMP-2; and with 0.5 μg PlGF-2 combined with 1.0 μg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Liu

Deng

Sun

et al. 2016

IJN

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“…When embedded within hydrogels, cells need to form a tissue-specific matrix that is capable of repairing or regenerating the damaged tissue. However, hydrogels often have inadequate mechanical properties, which are either unfavourable to embedded cells or make them too weak for application in the musculoskeletal system [5][6][7] .…”

mentioning

confidence: 99%

Reinforcement of hydrogels using three-dimensionally printed microfibres

et al. 2015

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“…Currently, the trend is to use composite carriers that provide the benefits of each class of materials. For example, semisynthetic polymers, which exhibit controlled release properties, were introduced due to their biocompatibility in combining with natural polymers, including polycaprolactone within collagen [105], PEGylated fibrinogen [106]. In another example, composites, that combined collagen to biphasic calcium phosphate, were superior to biphasic calcium phosphate alone for bone regeneration, while decreasing the incidence of burst release [107].…”

Section: Bmpmentioning

confidence: 99%

The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease

Makino¹,

Tsukazaki²,

Ukon³

et al. 2018

IJMS

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In this era of aging societies, the number of elderly individuals who undergo spinal arthrodesis for various degenerative diseases is increasing. Poor bone quality and osteogenic ability in older patients, due to osteoporosis, often interfere with achieving bone fusion after spinal arthrodesis. Enhancement of bone fusion requires shifting bone homeostasis toward increased bone formation and reduced resorption. Several biological enhancement strategies of bone formation have been conducted in animal models of spinal arthrodesis and human clinical trials. Pharmacological agents for osteoporosis have also been shown to be effective in enhancing bone fusion. Cytokines, which activate bone formation, such as bone morphogenetic proteins, have already been clinically used to enhance bone fusion for spinal arthrodesis. Recently, stem cells have attracted considerable attention as a cell source of osteoblasts, promising effects in enhancing bone fusion. Drug delivery systems will also need to be further developed to assure the safe delivery of bone-enhancing agents to the site of spinal arthrodesis. Our aim in this review is to appraise the current state of knowledge and evidence regarding bone enhancement strategies for spinal fusion for degenerative spinal disorders, and to identify future directions for biological bone enhancement strategies, including pharmacological, cell and gene therapy approaches.

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Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix

Cited by 98 publications

References 43 publications

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Reinforcement of hydrogels using three-dimensionally printed microfibres

The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease

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