Dose-dependent effects of combined IGF-I and TGF-β1 application in a sheep cervical spine fusion model

Kandziora, Frank; Pflugmacher, Robert; Scholz, Matti; Schäfer, Jan Hendrik; Schollmeier, Georg; Schmidmaier, Gerhard; Duda, Georg N.; Raschke, Michael J.; Haas, Norbert

doi:10.1007/s00586-002-0483-x

Cited by 21 publications

(7 citation statements)

References 65 publications

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“…Additionally, Kandziora et al[45] investigated the effects of IGF-1/TGF-beta-1 in a sheep anterolateral (C3-C4) interbody model using a titanium cage coated with a PDLLA carrier including no growth factors, as well as with different concentrations of IGF-1 and TGF-beta-1. The authors concluded that the application of IGF-1 and TGF-beta-1 by a PDLLA-coated cage significantly improves interbody bone formation in a dose dependent manner, as assessed via micro-CT and histomorphometrical analysis, at 12 wk postoperatively.…”

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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“…The amount of growth factor used depends on the size of the implants, as the growth factors are administered in a specific w/w ratio to the poly(D,L-lactide) scaffold. The w/w ratio that we used was based on previous experience ( Kandziora et al 2003 , Lamberg et al 2006 ). It is possible that even better results would be obtained with different ratios, and this is the subject of further investigation.…”

Section: Discussionmentioning

confidence: 99%

Effect of local TGF-β1 and IGF-1 release on implant fixation: comparison with hydroxyapatite coating

et al. 2009

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Background and purpose Hydroxyapatite (HA) coating stimulates the osseointegration of cementless orthopedic implants. Recently, locally released osteogenic growth factors have also been shown experimentally to stimulate osseointegration so that bone fills gaps around orthopedic implants. Here, we have compared the effect of local release of TGF-β 1 and IGF-1 with that of hydroxyapatite coating on implant fixation.Method Weight-bearing implants with a 0.75-mm surrounding gap were inserted bilaterally in the knees of 10 dogs. Growth factors were incorporated in a biodegradable poly(D,L-lactide) coating on porous coated titanium implants. Plasma-sprayed HA implants served as controls. The dogs were killed at 4 weeks and the implants were evaluated by mechanical push-out test and by histomorphometry.Results There was no difference in any of the mechanical parameters. Bone ongrowth was 3-fold higher for HA-coated implants (p < 0.001). For growth factor-coated implants, bone volume was 26% higher in the inner half of the gap and 28% higher in the outer half compared to HA (p < 0.03).Interpretation- The mechanical fixation of porous-coated titanium implants with local growth factor release is comparable to that of HA coating. While HA mainly stimulated bone ongrowth, local release of TGFβ 1 and IGF-1 stimulated gap healing.

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“…The magnitude of the accelerated healing is difficult to determine, as a variety of time points were not evaluated and the treated limbs did not approach intact biomechanical values. In addition, this combination was shown to enhance interbody spinal fusions when coated on titanium fusion cages [41][42][43]. FGF, delivered with a hyaluronan material, has also been evaluated in several preclinical models of fracture repair.…”

Section: Bone Tissue Engineering Using Growth Factorsmentioning

confidence: 99%

Protein-based tissue engineering in bone and cartilage repair

Wozney¹,

Seeherman²

2004

Current Opinion in Biotechnology

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Dose-dependent effects of combined IGF-I and TGF-β1 application in a sheep cervical spine fusion model

Cited by 21 publications

References 65 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

Effect of local TGF-β1 and IGF-1 release on implant fixation: comparison with hydroxyapatite coating

Protein-based tissue engineering in bone and cartilage repair

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