Effect of Freeze-Dried Allograft Bone With Human Basic Fibroblast Growth Factor Containing a Collagen-Binding Domain From Clostridium histolyticum Collagenase on Bone Formation After Lumbar Posterolateral Fusion Surgery in Rats

Inoue, Gen; Uchida, Katsuhisa; Matsushita, Osamu; Fujimaki, Hisako; Saito, Wataru; Miyagi, Masayuki; Sekiguchi, Hiroyuki; Nishi, Nozomu; Ohtori, Seiji; Yogoro, Mizuki; Takaso, Masashi

doi:10.1097/brs.0000000000002074

Cited by 8 publications

(9 citation statements)

References 35 publications

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“…Inoue et al[38] investigated the effects of an engineered bFGF on spinal fusion in a Sprague-Dawley rat posterolateral lumbar (L4-L5) model. Two fusion groups were studied: femoral freeze-dried bone allograft incubated with an engineered bFGF or with phosphate buffered saline.…”

Section: Resultsmentioning

confidence: 99%

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Investigational growth factors utilized in animal models of spinal fusion: Systematic review

Cottrill¹,

Ahmed²,

Lessing³

et al. 2019

WJO

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BACKGROUND Over 400000 Americans annually undergo spinal fusion surgeries, yet up to 40% of these procedures result in pseudoarthrosis even with iliac crest autograft, the current “gold standard” treatment. Tissue engineering has the potential to solve this problem via the creation of bone grafts involving bone-promoting growth factors ( e.g ., bone morphogenetic protein 2). A broad assessment of experimental growth factors is important to inform future work and clinical potential in this area. To date, however, no study has systematically reviewed the investigational growth factors utilized in preclinical animal models of spinal fusion. AIM To review all published studies assessing investigational growth factors for spinal fusion in animal models and identify promising agents for translation. METHODS We conducted a systematic review of the literature using PubMed, Embase, Cochrane Library, and Web of Science databases with searches run on May 29 th , 2018. The search query was designed to include all non-human, preclinical animal models of spinal fusion reported in the literature without a timespan limit. Extracted data for each model included surgical approach, level of fusion, animal species and breed, animal age and sex, and any other relevant characteristics. The dosages/sizes of all implant materials, spinal fusion rates, and follow-up time points were recorded. The data were analyzed and the results reported in tables and text. PRISMA guidelines were followed for this systematic review. RESULTS Twenty-six articles were included in this study, comprising 14 experimental growth factors: AB204 ( n = 1); angiopoietin 1 ( n = 1); calcitonin ( n = 3); erythropoietin ( n = 1); basic fibroblast growth factor ( n = 1); growth differentiation factor 5 ( n = 4), combined insulin-like growth factor 1 + transforming growth factor beta ( n = 4); insulin ( n = 1); NELL-1 ( n = 5); noggin ( n = 1); P-15 ( n = 1); peptide B2A ( n = 2); and secreted phosphoprotein 24 ( n = 1). The fusion rates of the current gold standard treatment (autologous iliac crest bone graft, ICBG) and the leading clinically used growth factor (BMP-2) ranged widely in the included studies, from 0-100% for ICBG and from 13%-100% for BMP-2. Among the identified growth factors, calcitonin, GDF-5, NELL-1, and P-15 resulted in fusion rates of 100% in some cases. In addition, six growth factors - AB204, angiopoietin 1, GDF-5, insulin, NELL-1, and peptide B2A - resulted in significantly enhanced fusion rates compared to ICBG, BMP...

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Section: Resultsmentioning

confidence: 99%

“…As a result of this heterogeneity, directly comparing end points ( i.e ., rates of fusion) across multiple studies is not possible. Further, three studies did not report fusion rates[36,38,45], limiting the interpretability of those studies. In addition, our review excludes growth factors that have been studied clinically in spinal fusion.…”

Section: Discussionmentioning

confidence: 99%

Investigational growth factors utilized in animal models of spinal fusion: Systematic review

Cottrill¹,

Ahmed²,

Lessing³

et al. 2019

WJO

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“…As one of the most abundant ECM proteins, collagens represent good binding targets for engineering GFs for delivery to collagen-rich tissues. For example, a bacterial collagen-binding domain (CBD), was fused to fibroblast growth factor-2 (FGF-2), allowing improved bone formation in a spinal fusion model (Inoue et al, 2017). In another study, CBD-fused FGF-2 showed the ability to induce significantly higher mesenchymal cell proliferation and callus formation in a mice fracture model compared to wild-type FGF-2 (Sekiguchi et al, 2018).…”

Section: Engineering Gfs For Non-covalent Interaction To Biomaterialsmentioning

confidence: 99%

Growth Factor Engineering Strategies for Regenerative Medicine Applications

Xue-ping

Zhao

Lash

et al. 2020

Front. Bioeng. Biotechnol.

178

130

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Growth factors are critical molecules for tissue repair and regeneration. Therefore, recombinant growth factors have raised a lot of hope for regenerative medicine applications. While using growth factors to promote tissue healing has widely shown promising results in pre-clinical settings, their success in the clinic is not a forgone conclusion. Indeed, translation of growth factors is often limited by their short half-life, rapid diffusion from the delivery site, and low cost-effectiveness. Trying to circumvent those limitations by the use of supraphysiological doses has led to serious side-effects in many cases and therefore innovative technologies are required to improve growth factorbased regenerative strategies. In this review, we present protein engineering approaches seeking to improve growth factor delivery and efficacy while reducing doses and side effects. We focus on engineering strategies seeking to improve affinity of growth factors for biomaterials or the endogenous extracellular matrix. Then, we discuss some examples of increasing growth factor stability and bioactivity, and propose new lines of research that the field of growth factor engineering for regenerative medicine may adopt in the future.

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“…Rats are lower cost, facilitate shorter operation times and higherthroughput studies, and most importantly, enable more in-depth analyses of the biology underlying fusion due to a wider availability of cellular and molecular tools. Various fusion therapies have been studied in rat models, including: a range of bone graft substitute and extension materials; systemic and localized delivery of osteogenic growth factors and/or osteoporosis therapies; and, stem cell transplantation therapies [4][5][6][7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Comparing the Efficacy of Syngeneic Iliac and Femoral Allografts with Iliac Crest Autograft in a Rat Model of Lumbar Spinal Fusion

Holmes

Elder

Ishida

et al. 2020

Preprint

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Background: Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.Methods: Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft; syngeneic iliac crest allograft; and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.Results: Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow. Conclusions: This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.

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Effect of Freeze-Dried Allograft Bone With Human Basic Fibroblast Growth Factor Containing a Collagen-Binding Domain From Clostridium histolyticum Collagenase on Bone Formation After Lumbar Posterolateral Fusion Surgery in Rats

Abstract: N/A.

Cited by 8 publications

References 35 publications

Investigational growth factors utilized in animal models of spinal fusion: Systematic review

Investigational growth factors utilized in animal models of spinal fusion: Systematic review

Growth Factor Engineering Strategies for Regenerative Medicine Applications

Comparing the Efficacy of Syngeneic Iliac and Femoral Allografts with Iliac Crest Autograft in a Rat Model of Lumbar Spinal Fusion

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