Efficacy of Escherichia coli -derived recombinant human bone morphogenetic protein-2 in posterolateral lumbar fusion: an open, active-controlled, randomized, multicenter trial

Cho, Jae-Hwan; Lee, Jae Hyup; Yeom, Jin Sup; Chang, Bong Soon; Yang, Jae Jun; Koo, Ki Hyoung; Hwang, Chang Ju; Lee, Kwang Bok; Kim, Ho-Joong; Lee, Choon-Ki; Kim, Hyoungmin; Suk, Kyung Soo; Nam, Woo Dong; Han, Jumi

doi:10.1016/j.spinee.2017.06.023

Cited by 37 publications

(41 citation statements)

References 49 publications

(53 reference statements)

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“…However, to date, it is also acknowledged that BMP-2 remains a powerful activator of bone repair, whose delivery needs to be further optimized. Alternative sources of BMP-2 combined with ceramics are emerging, such as those produced in CHO-cells [74] or in E-coli [75, 76].…”

Section: Bone Graft Substitutes Combined With Active Biomoleculesmentioning

confidence: 99%

Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives

et al. 2018

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Bone fractures are the most common traumatic injuries in humans. The repair of bone fractures is a regenerative process that recapitulates many of the biological events of embryonic skeletal development. Most of the time it leads to successful healing and the recovery of the damaged bone. Unfortunately, about 5-10% of fractures will lead to delayed healing or non-union, more so in the case of co-morbidities such as diabetes. In this article, we review the different strategies to heal bone defects using synthetic bone graft substitutes, biologically active substances and stem cells. The majority of currently available reviews focus on strategies that are still at the early stages of development and use mostly in vitro experiments with cell lines or stem cells. Here, we focus on what is already implemented in the clinics, what is currently in clinical trials, and what has been tested in animal models. Treatment approaches can be classified in three major categories: i) synthetic bone graft substitutes (BGS) whose architecture and surface can be optimized; ii) BGS combined with bioactive molecules such as growth factors, peptides or small molecules targeting bone precursor cells, bone formation and metabolism; iii) cell-based strategies with progenitor cells combined or not with active molecules that can be injected or seeded on BGS for improved delivery. We review the major types of adult stromal cells (bone marrow, adipose and periosteum derived) that have been used and compare their properties. Finally, we discuss the remaining challenges that need to be addressed to significantly improve the healing of bone defects.

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Section: Bone Graft Substitutes Combined With Active Biomoleculesmentioning

confidence: 99%

Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives

et al. 2018

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“…At the cellular level, it can trigger a healing cascade, induce MSCs to differentiate into osteoblasts or chondroblasts, and promote osteoblast proliferation [ 295 , 296 ]. Accordingly, it has been frequently incorporated into scaffolds for applications ranging from spinal fusion [ 297 , 298 ] to dental and craniofacial regeneration [ [299] , [300] , [301] ]. However, a few studies have found that the direct delivery of cytokines to bone defects could cause individual differences in repair effects.…”

Section: Bioactive Molecular Delivery Based On Bone-healing Mechanismmentioning

confidence: 99%

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds

Zhu

Zhang

Miao

et al. 2021

Bioactive Materials

283

214

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Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.

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“…Using genetic recombination with E. coli , much larger amounts of rhBMP-2 can be produced at low cost; however, E. coli -derived rhBMP-2 is not glycosylated and shows reduced biological activity [18]. Nonetheless, recent pre-clinical and clinical studies using E. coli -derived rhBMP-2 have shown successful results in bone regeneration in orthopedic and bone augmentation procedures in dentistry [19,20,21].…”

Section: Rhbmp-2 Delivery In Protein Formmentioning

confidence: 99%

BMP-2 Gene Delivery-Based Bone Regeneration in Dentistry

Park

Kim

et al. 2019

Pharmaceutics

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Bone morphogenetic protein-2 (BMP-2) is a potent growth factor affecting bone formation. While recombinant human BMP-2 (rhBMP-2) has been commercially available in cases of non-union fracture and spinal fusion in orthopaedics, it has also been applied to improve bone regeneration in challenging cases requiring dental implant treatment. However, complications related to an initially high dosage for maintaining an effective physiological concentration at the defect site have been reported, although an effective and safe rhBMP-2 dosage for bone regeneration has not yet been determined. In contrast to protein delivery, BMP-2 gene transfer into the defect site induces BMP-2 synthesis in vivo and leads to secretion for weeks to months, depending on the vector, at a concentration of nanograms per milliliter. BMP-2 gene delivery is advantageous for bone wound healing process in terms of dosage and duration. However, safety concerns related to viral vectors are one of the hurdles that need to be overcome for gene delivery to be used in clinical practice. Recently, commercially available gene therapy has been introduced in orthopedics, and clinical trials in dentistry have been ongoing. This review examines the application of BMP-2 gene therapy for bone regeneration in the oral and maxillofacial regions and discusses future perspectives of BMP-2 gene therapy in dentistry.

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Efficacy of Escherichia coli -derived recombinant human bone morphogenetic protein-2 in posterolateral lumbar fusion: an open, active-controlled, randomized, multicenter trial

Cited by 37 publications

References 49 publications

Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives

Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds

BMP-2 Gene Delivery-Based Bone Regeneration in Dentistry

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