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Article ; Online: BMP-2 (and partially GDF-5) coating significantly accelerates and augments bone formation close to hydroxyapatite/tricalcium-phosphate/brushite implant cylinders for tibial bone defects in senile, osteopenic sheep.

Sachse, André / Hasenbein, Ines / Hortschansky, Peter / Schmuck, Klaus D / Maenz, Stefan / Illerhaus, Bernhard / Kuehmstedt, Peter / Ramm, Roland / Huber, René / Kunisch, Elke / Horbert, Victoria / Gunnella, Francesca / Roth, Andreas / Schubert, Harald / Kinne, Raimund W

Journal of materials science. Materials in medicine

2023 Volume 34, Issue 7, Page(s) 31

Abstract: Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) ... ...

Abstract	Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side). Three, 6, and 9 months post-operation (n = 6 each group), bone structure and formation were analyzed in vivo by X-ray and ex vivo by osteodensitometry, histomorphometry, and micro-computed tomography (micro-CT) at 3 and 9 months. Semi-quantitative X-ray evaluation showed significantly increasing bone densities around all implant cylinders over time. High-dose BMP-2-coated cylinders (3 and 9 months) and low-dose GDF-5-coated cylinders (3 and 6 months) demonstrated significantly higher densities than controls (dose-dependent for BMP-2 at 3 months). This was confirmed by osteodensitometry at 9 months for high-dose BMP-2-coated cylinders (and selected GDF-5 groups), and was again dose-dependent for BMP-2. Osteoinduction by BMP-2 was most pronounced in the adjacent bone marrow (dynamic histomorphometry/micro-CT). BMP-2 (and partially GDF-5) significantly increased the bone formation in the vicinity of HA/TCP/DCPD cylinders used to fill tibial bone defects in senile osteopenic sheep and may be suitable for surgical therapy of critical size, non-load-bearing bone defects in cases of failed tibial head fracture or defect healing.
MeSH term(s)	Female ; Animals ; Sheep ; Osteogenesis ; Durapatite/chemistry ; Bone Regeneration ; Growth Differentiation Factor 5 ; X-Ray Microtomography ; Calcium Phosphates/chemistry ; Hydroxyapatites
Chemical Substances	calcium phosphate, dibasic, dihydrate (O7TSZ97GEP) ; Durapatite (91D9GV0Z28) ; Growth Differentiation Factor 5 ; tricalcium phosphate (K4C08XP666) ; Calcium Phosphates ; hydroxyapatite-beta tricalcium phosphate ; Hydroxyapatites
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1031752-1
ISSN	1573-4838 ; 0957-4530
ISSN (online)	1573-4838
ISSN	0957-4530
DOI	10.1007/s10856-023-06734-2
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Zs.A 3040: Show issues

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Article: In Vitro Release of Bioactive Bone Morphogenetic Proteins (GDF5, BB-1, and BMP-2) from a PLGA Fiber-Reinforced, Brushite-Forming Calcium Phosphate Cement.

Gunnella, Francesca / Kunisch, Elke / Horbert, Victoria / Maenz, Stefan / Bossert, Jörg / Jandt, Klaus D / Plöger, Frank / Kinne, Raimund W

Pharmaceutics

2019 Volume 11, Issue 9

Abstract: Bone regeneration of sheep lumbar osteopenia is promoted by targeted delivery of bone morphogenetic proteins (BMPs) via a biodegradable, brushite-forming calcium-phosphate-cement (CPC) with stabilizing poly(l-lactide- ...

Abstract	Bone regeneration of sheep lumbar osteopenia is promoted by targeted delivery of bone morphogenetic proteins (BMPs) via a biodegradable, brushite-forming calcium-phosphate-cement (CPC) with stabilizing poly(l-lactide-
Language	English
Publishing date	2019-09-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics11090455
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Article ; Online: The poly (l-lactid-co-glycolide; PLGA) fiber component of brushite-forming calcium phosphate cement induces the osteogenic differentiation of human adipose tissue-derived stem cells.

Kunisch, Elke / Gunnella, Francesca / Wagner, Stefanie / Dees, Franziska / Maenz, Stefan / Bossert, Jörg / Jandt, Klaus D / Kinne, Raimund W

Biomedical materials (Bristol, England)

2019 Volume 14, Issue 5, Page(s) 55012

Abstract: A brushite-forming calcium phosphate cement (CPC) was mechanically stabilized by addition of poly (l-lactid-co-glycolide; PLGA) fibers (≤10% w/w). It proved highly biocompatible and its fiber component enhanced bone formation in a sheep lumbar ... ...

Abstract	A brushite-forming calcium phosphate cement (CPC) was mechanically stabilized by addition of poly (l-lactid-co-glycolide; PLGA) fibers (≤10% w/w). It proved highly biocompatible and its fiber component enhanced bone formation in a sheep lumbar vertebroplasty model. However, possible effects on the osteogenic differentiation of resident mesenchymal stem cells (MSCs) remained unexplored. The present study used a novel approach, simultaneously analyzing the influence of a solid CPC scaffold and its relatively low PLGA proportion (a mimicry of natural bone) on osteogenic, chondrogenic, and adipogenic differentiation, as well as the pluripotency of human adipose tissue-derived mesenchymal stem cells (hASCs). hASCs were cultured on CPC discs with/without PLGA fibers (5% and 10%) in the absence of osteogenic medium for 3, 7, and 14 d. Gene expression of osteogenic markers (Runx2, osterix, alkaline phosphatase, collagen I, osteonectin, osteopontin, osteocalcin), chondrogenic markers (collagen II, Sox9, aggrecan), adipogenic markers (PPARG, Leptin, and FABP4), and pluripotency markers (Nanog, Tert, Rex) was analyzed by RT-PCR. The ability of hASCs to synthesize alkaline phosphatase was also evaluated. Cell number and viability were determined by fluorescein diacetate/propidium iodide staining. Compared to pure CPC, cultivation of hASCs on fiber-reinforced CPC transiently induced the gene expression of Runx2 and osterix (day 3), and long-lastingly augmented the expression of alkaline phosphatase (and its enzyme activity), collagen I, and osteonectin (until day 14). In contrast, augmented expression of all chondrogenic, adipogenic, and pluripotency markers was limited to day 3, followed by significant downregulation. Cultivation of hASCs on fiber-reinforced CPC reduced the cell number, but not the proportion of viable cells (viability > 95%). The PLGA component of fiber-reinforced, brushite-forming CPC supports long-lasting osteogenic differentiation of hASCs, whereas chondrogenesis, adipogenesis, and pluripotency are initially augmented, but subsequently suppressed. In view of parallel animal results, PLGA fibers may represent an interesting clinical target for future improvement of CPC- based bone regeneration.
MeSH term(s)	Adipose Tissue/cytology ; Adult ; Alkaline Phosphatase/metabolism ; Animals ; Bone Cements ; Bone Regeneration/drug effects ; Calcium Phosphates/chemistry ; Cell Differentiation ; Cell Lineage ; Cell Survival ; Cells, Cultured ; Chondrogenesis ; Female ; Humans ; Lumbar Vertebrae/physiopathology ; Male ; Mesenchymal Stem Cells/cytology ; Middle Aged ; Models, Animal ; Osteogenesis/drug effects ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Sheep ; Vertebroplasty/instrumentation ; Vertebroplasty/methods
Chemical Substances	Bone Cements ; Calcium Phosphates ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Alkaline Phosphatase (EC 3.1.3.1) ; calcium phosphate, dibasic, dihydrate (O7TSZ97GEP)
Language	English
Publishing date	2019-08-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2265222-X
ISSN	1748-605X ; 1748-6041
ISSN (online)	1748-605X
ISSN	1748-6041
DOI	10.1088/1748-605X/ab3544
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Article: Performance of Calcium Phosphate Cements in the Augmentation of Sheep Vertebrae-An Ex Vivo Study.

Kinne, Raimund W / Gunnella, Francesca / Kunisch, Elke / Heinemann, Sascha / Nies, Berthold / Maenz, Stefan / Horbert, Victoria / Illerhaus, Bernhard / Huber, René / Firkowska-Boden, Izabela / Bossert, Jörg / Jandt, Klaus D / Sachse, André / Bungartz, Matthias / Brinkmann, Olaf

Materials (Basel, Switzerland)

2021 Volume 14, Issue 14

Abstract: Oil-based calcium phosphate cement (Paste-CPC) shows not only prolonged shelf life and injection times, but also improved cohesion and reproducibility during application, while retaining the advantages of fast setting, mechanical strength, and ... ...

Abstract	Oil-based calcium phosphate cement (Paste-CPC) shows not only prolonged shelf life and injection times, but also improved cohesion and reproducibility during application, while retaining the advantages of fast setting, mechanical strength, and biocompatibility. In addition, poly(L-lactide-co-glycolide) (PLGA) fiber reinforcement may decrease the risk for local extrusion. Bone defects (diameter 5 mm; depth 15 mm) generated ex vivo in lumbar (L) spines of female Merino sheep (2-4 years) were augmented using: (i) water-based CPC with 10% PLGA fiber reinforcement (L3); (ii) Paste-CPC (L4); or (iii) clinically established polymethylmethacrylate (PMMA) bone cement (L5). Untouched (L1) and empty vertebrae (L2) served as controls. Cement performance was analyzed using micro-computed tomography, histology, and biomechanical testing. Extrusion was comparable for Paste-CPC(-PLGA) and PMMA, but significantly lower for CPC + PLGA. Compressive strength and Young's modulus were similar for Paste-CPC and PMMA, but significantly higher compared to those for empty defects and/or CPC + PLGA. Expectedly, all experimental groups showed significantly or numerically lower compressive strength and Young's modulus than those of untouched controls. Ready-to-use Paste-CPC demonstrates a performance similar to that of PMMA, but improved biomechanics compared to those of water-based CPC + PLGA, expanding the therapeutic arsenal for bone defects. O, significantly lower extrusion of CPC + PLGA fibers into adjacent lumbar spongiosa may help to reduce the risk of local extrusion in spinal surgery.
Language	English
Publishing date	2021-07-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma14143873
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Book ; Online ; Thesis: Biotechnologically modified calcium phosphate cement for the stabilization of osteoporotic vertebral compression fractures

Gunnella, Francesca [Verfasser] / Kinne, Raimund W. [Gutachter] / Sittinger, Michael [Gutachter] / Wetzker, Reinhard [Gutachter]

2019

Author's details	Francesca Gunnella ; Gutachter: Raimund K. Kinne, Michael Sittinger, Reinhard Wetzker
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Friedrich-Schiller-Universität Jena
Publishing place	Jena
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: The old sheep: a convenient and suitable model for senile osteopenia.

Maenz, Stefan / Brinkmann, Olaf / Hasenbein, Ines / Braun, Christina / Kunisch, Elke / Horbert, Victoria / Gunnella, Francesca / Sachse, André / Bischoff, Sabine / Schubert, Harald / Jandt, Klaus D / Bossert, Jörg / Driesch, Dominik / Kinne, Raimund W / Bungartz, Matthias

Journal of bone and mineral metabolism

2020 Volume 38, Issue 5, Page(s) 620–630

Abstract: Introduction: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. ... ...

Abstract	Introduction: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. Materials and methods: The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10 years; n = 41) and young animals (2-4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. Results: In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). Conclusion: Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.
MeSH term(s)	Animals ; Biomechanical Phenomena ; Bone Density ; Bone Diseases, Metabolic/pathology ; Bone Diseases, Metabolic/physiopathology ; Cancellous Bone/pathology ; Cancellous Bone/physiopathology ; Compressive Strength ; Disease Models, Animal ; Elastic Modulus ; Female ; Lumbar Vertebrae/pathology ; Lumbar Vertebrae/physiopathology ; Osteogenesis ; Sheep/physiology
Language	English
Publishing date	2020-04-15
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-020-01098-x
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Zs.A 4894: Show issues

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Conference proceedings: GDF5 significantly augments the bone formation induced by an injectable, PLGA-fiber reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia

Gunnella, Francesca / Kunisch, Elke / Mänz, Stefan / Illerhaus, Bernhard / Bungartz, Matthias / Brinkmann, Olaf / Bossert, Jörg / Kinne, Raimund W.

2017 , Page(s) PO12–520

Event/congress	Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017); Berlin; ; Berufsverband der Fachärzte für Orthopädie; 2017
Keywords	Medizin, Gesundheit ; osteoporotic vertebral fracture ; calcium phosphate cement ; bone regeneration ; large animal model sheep ; vertebroplasty ; growth factor
Publishing date	2017-10-23
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/17dkou613
Database	German Medical Science

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Article ; Online: Enhanced bone formation in sheep vertebral bodies after minimally invasive treatment with a novel, PLGA fiber-reinforced brushite cement.

Maenz, Stefan / Brinkmann, Olaf / Kunisch, Elke / Horbert, Victoria / Gunnella, Francesca / Bischoff, Sabine / Schubert, Harald / Sachse, Andre / Xin, Long / Günster, Jens / Illerhaus, Bernhard / Jandt, Klaus D / Bossert, Jörg / Kinne, Raimund W / Bungartz, Matthias

The spine journal : official journal of the North American Spine Society

2017 Volume 17, Issue 5, Page(s) 709–719

Abstract: Background context: Injectable, brushite-forming calcium phosphate cements (CPC) show potential for bone replacement, but they exhibit low mechanical strength. This study tested a CPC reinforced with poly(l-lactide-co-glycolide) acid (PLGA) fibers in a ... ...

Abstract	Background context: Injectable, brushite-forming calcium phosphate cements (CPC) show potential for bone replacement, but they exhibit low mechanical strength. This study tested a CPC reinforced with poly(l-lactide-co-glycolide) acid (PLGA) fibers in a minimally invasive, sheep lumbar vertebroplasty model. Purpose: The study aimed to test the in vivo biocompatibility and osteogenic potential of a PLGA fiber-reinforced, brushite-forming CPC in a sheep large animal model. Study design/setting: This is a prospective experimental animal study. Methods: Bone defects (diameter: 5 mm) were placed in aged, osteopenic female sheep, and left empty (L2) or injected with pure CPC (L3) or PLGA fiber-reinforced CPC (L4; fiber diameter: 25 µm; length: 1 mm; 10% [wt/wt]). Three and 9 months postoperation (n=20 each), the structural and functional CPC effects on bone regeneration were documented ex vivo by osteodensitometry, histomorphometry, micro-computed tomography (micro-CT), and biomechanical testing. Results: Addition of PLGA fibers enhanced CPC osteoconductivity and augmented bone formation. This was demonstrated by (1) significantly enhanced structural (bone volume/total volume, shown by micro-CT and histomorphometry; 3 or 9 months) and bone formation parameters (osteoid volume and osteoid surface; 9 months); (2) numerically enhanced bone mineral density (3 and 9 months) and biomechanical compression strength (9 months); and (3) numerically decreased bone erosion (eroded surface; 3 and 9 months). Conclusions: The PLGA fiber-reinforced CPC is highly biocompatible and its PLGA fiber component enhanced bone formation. Also, PLGA fibers improve the mechanical properties of brittle CPC, with potential applicability in load-bearing areas.
MeSH term(s)	Animals ; Bone Cements/adverse effects ; Bone Cements/chemistry ; Bone Regeneration ; Calcium Phosphates/chemistry ; Female ; Lactic Acid/chemistry ; Osteogenesis ; Polyglycolic Acid/chemistry ; Sheep ; Vertebroplasty/adverse effects ; Vertebroplasty/methods
Chemical Substances	Bone Cements ; Calcium Phosphates ; polylactic acid-polyglycolic acid copolymer ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT) ; calcium phosphate, dibasic, dihydrate (O7TSZ97GEP)
Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2037072-6
ISSN	1878-1632 ; 1529-9430
ISSN (online)	1878-1632
ISSN	1529-9430
DOI	10.1016/j.spinee.2016.11.006
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Zs.A 5898: Show issues

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Conference proceedings: PLGA-fiber reinforcement of injectable calcium phosphate cement enhances bone regeneration in an in vivo vertebral body augmentation model

Gunnella, Francesca / Mänz, Stefan / Illerhaus, Bernhard / Bungartz, Matthias / Brinkmann, Olaf / Kunisch, Elke / Bossert, Jörg / Kinne, Raimund W.

2016 , Page(s) PO30–463

Event/congress	Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2016); Berlin; ; Berufsverband der Fachärzte für Orthopädie; 2016
Keywords	Medizin, Gesundheit ; Calcium phosphate cement ; fiber reinforcement ; bone regeneration ; large animal model sheep ; vertebroplasty
Publishing date	2016-10-10
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/16dkou796
Database	German Medical Science

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Article ; Online: GDF5 significantly augments the bone formation induced by an injectable, PLGA fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia.

Bungartz, Matthias / Kunisch, Elke / Maenz, Stefan / Horbert, Victoria / Xin, Long / Gunnella, Francesca / Mika, Joerg / Borowski, Juliane / Bischoff, Sabine / Schubert, Harald / Sachse, Andre / Illerhaus, Bernhard / Günster, Jens / Bossert, Jörg / Jandt, Klaus D / Plöger, Frank / Kinne, Raimund W / Brinkmann, Olaf

The spine journal : official journal of the North American Spine Society

2017 Volume 17, Issue 11, Page(s) 1685–1698

Abstract: Background context: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone ... ...

Abstract	Background context: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration. Purpose: In the present study, an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing the bone morphogenetic protein GDF5 was tested in a sheep lumbar osteopenia model. Study design/setting: This is a prospective experimental animal study. Methods: Defined bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep. Defects were treated with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of GDF5 (L5; CPC+fibers+GDF5; 1, 5, 100, and 500 µg GDF5; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months postoperation, structural and functional effects of the CPC (±GDF5) were assessed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralized surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. Results: Compared with untouched controls (L1), both CPC+fibers (L4) and CPC+fibers+GDF5 (L5) numerically or significantly improved all parameters of bone formation, bone resorption, and bone structure. These significant effects were observed both at 3 and 9 months, but for some parameters they were less pronounced at 9 months. Compared with CPC without GDF5, additional significant effects of CPC with GDF5 were demonstrated for BMD and parameters of bone formation and structure (bone volume/total volume, trabecular thickness, and trabecular number, as well as mineralized surface/bone surface). The GDF5 effects were dose-dependent (predominantly in the 5-100 µg range) at 3 and 9 months. Conclusions: GDF5 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. The results indicated that a local dose as low as ≤100 µg GDF5 may be sufficient to augment middle to long-term bone formation. The novel CPC+GDF5 combination may thus qualify as an alternative to the bioinert, supraphysiologically stiff poly(methyl methacrylate) cement currently applied for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.
MeSH term(s)	Animals ; Bone Cements/chemistry ; Bone Cements/therapeutic use ; Bone Density ; Bone Diseases, Metabolic/drug therapy ; Bone Regeneration ; Calcium Phosphates/chemistry ; Compressive Strength ; Female ; Growth Differentiation Factor 5/administration & dosage ; Growth Differentiation Factor 5/therapeutic use ; Lumbosacral Region/pathology ; Polymethyl Methacrylate/chemistry ; Sheep
Chemical Substances	Bone Cements ; Calcium Phosphates ; Growth Differentiation Factor 5 ; Polymethyl Methacrylate (9011-14-7) ; tricalcium phosphate (K4C08XP666) ; calcium phosphate, dibasic, dihydrate (O7TSZ97GEP)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2037072-6
ISSN	1878-1632 ; 1529-9430
ISSN (online)	1878-1632
ISSN	1529-9430
DOI	10.1016/j.spinee.2017.06.007
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