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

doi:10.5312/wjo.v10.i4.176

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World Journal of Orthopedics

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Systematic Review

World J Orthop. Apr 18, 2019; 10(4): 176-191
Published online Apr 18, 2019. doi: 10.5312/wjo.v10.i4.176

Table 4 Experimental models and rates of bony fusion for each included study

Growth factor	Animal(n)	Levels (a/p)¹	Experimental groups	Fusion rate
AB204
Zheng et al[32], 2017	Dog (n = 56)	L1-L2, L4-L5 (p)	(1) BCP; (2) BCP + rhBMP-2; (3) BCP + AB204	(1) 6.3%; (2) 15%; (3) 90%²
COMP-Ang-1
Park et al[33], 2011	Rat (n = 56)	L3-L5 (p)	(1) ICBG; (2) ICBG + bovine serum albumin-impregnated collagen sponge; (3) ICBG + COMP-Ang-1-impregnated collagen sponge	(2) 38.9%; (2) 42.1%; (3) 89.5%²
Calcitonin
Babat et al[34], 2005	Rabbit (n = 56)	L5-L6 (p)	(1) ICBG; (2) ICBG + calcitonin; (3) ICBG + pamidronate	(1) 56%; (2) 68%; (3) 37%
Liu et al[35], 2012	Rabbit (n = 32)	L4-L5, L6-L7 (p)	(1) ICBG; (2) ICBG + calcitonin; (3) ICBG + interspinous fixation (steel wire); (4) ICBG + interspinous fixation (steel wire) + calcitonin	(1) 75%; (2) 100%; (3) 75% 100%
Liu et al[36], 2015	Rat (n = 50)	L4-L5 (p)	(1) Sham surgery + saline vehicle; (2) Ovariectomy + saline vehicle; (3) Spinal fusion (ICBG) + saline vehicle; (4) Ovariectomy + Spinal fusion (ICBG); (5) Ovariectomy + Spinal fusion (ICBG) + calcitonin	Not reported
EPO
Rolfing et al[37], 2011	Rabbit (n = 28)	L5-L6 (p)	(1) ICBG + Epoetin beta subcutaneous injection; (2) ICBG + Saline subcutaneous injection	(1) 86%; (2) 71%
bFGF
Inoue et al[38], 2017	Rat (n = 20)	L4-L5 (p)	(1) Allograft; (2) Allograft + bFGF	Not reported
GDF-5
Spiro et al[39], 2000	Baboon (n = 36)	L4-L5 (p)	(1) ICBG; (2) Collagen matrix strips; (3) Collagen matrix strips + rhGDF-5 (500μg/cm³); (4) Collagen matrix strips + rhGDF-5 (1500μg/cm³)	(1) 22%; (2) 0%; (3) 44%; (4) 11%
Spiro et al[40], 2001	Rabbit (n = 31)	L5-L6 (p)	(1) ICBG; (2) Hydroxyapatite-mineralized collagen matrix (Matrix); (3) Matrix + bone marrow; (4) Healos strips + rhGDF-5 (0.1 mg/cc); (5) Healos strips + rhGDF-5 (1.0 mg/cc); (6) Non-crosslinked collagen strips + rhGDF-5 (0.1 mg/cc); (7) Non-crosslinked collagen strips + rhGDF-5 (1.0 mg/cc); (8) Collagen fiber slurry + rhGDF-5 (0.1 mg/cc); (9) Collagen fiber slurry + rhGDF-5 (1.0 mg/cc)	(1) 33%; (2) 0%; (3) 0%; (4) 0%; (5) 67%; (6) 75%; (7) 80%; (8) 25%; (9) 0%
Jahng et al[41], 2004	Sheep (n = 8)	L4-L5 (p)	(1) ICBG; (2) Healos + GDF-5	(1)100%; (2) 100%
Magit et al[42], 2006	Rabbit (n = 65)	L5-L6 (p)	(1) ICBG; (2) Healos; (3) Healos + rhGDF-5 (0.5 mg/cc); (4) Healos + rhGDF-5 (1 mg/cc); (5) Healos + rhGDF-5 (1.5 mg/cc)	(1) 38%; (2) 0%; (3) 100%²; (4) 100%²; (5) 100%²
IGF-1/TGF-β
Kandziora et al[43], 2002	Sheep (n = 32)	C3-C4 (a)	(1) Titanium cage (Cage); (2) Cage + ICBG; (3) Cage + PDLLA + BMP-2; (4) Cage + PDLLA + rh-IGF-1/TGF-β	(1) 0%; (2) 13%; (3) 13%; (4) 13%
Kandziora et al[44], 2002	Sheep (n = 32)	C3-C4 (a)	(1) ICBG; (2) Titanium cage (Cage); (3) Cage + PDLLA; (4) Cage + PDLLA + rh-IGF-1/TGF-β	(1) 0%; (2) 0%; (3) 0%; (4) 12.5%
Kandziora et al[45], 2003	Sheep (n = 32)	C3-C4 (a)	(1) Titanium cage + PDLLA (Cage); (2) Cage + rh-IGF-1/TGF-β (2.5/0.5%); (3) Cage + rh-IGF-1/TGF-β (5/1%); (4) Cage + rh-IGF-1/TGF-β (10/2%)	Not reported
Gu et al[46], 2006	Goat (n = 32)	C3-C4 (a)	(1) ICBG; (2) Titanium cage (Cage); (3) Cage + hydroxyapatite; (4) Cage + IGF-1/TGF-β (5/1%)	(1) 0%; (2) 25%; (3) 38%; (4) 63%
Insulin
Koerner et al[47], 2013	Rat (n = 19)	L4-L5 (p)	(1) ICBG + 100% palmitic acid; (2) ICBG + Linplant (95% palmitic acid and 5% bovine insulin)	(1) 11%; (2) 60%²
NELL-1
Lee et al[48], 2009	Rat (n = 10)	L4-L5 (p)	(1) Demineralized bone putty (Putty) + PBS; (2) Putty + rh-NELL-1	(1) 0%; (2) 60%
Li et al[49], 2010	Rat (n = 24)	L4-L5 (p)	(1) DBX + PBS; (2) DBX + NELL-1 (2.5 g); (3) DBX + NELL-1 (5 μg)	(1) 25%; (2) 75%; (3) 88%
Siu et al[50], 2011	Sheep (n = 32)	L3-L4 L5-L6 (a)	(1) Cage + DBM; (2) Cage + inactivated DBM; (3) Cage + DBM + NELL-1 (0.3 mg/mL) Cage + DBM + NELL-1 (0.6 mg/mL); (4) Cage + inactivated; (5) DBM + NELL-1 (0.3 mg/mL); (6) Cage + inactivated DBM + NELL-1 (0.3 mg/mL)	(1) 50%; (2) 50%; (3) 87.5%²; (4) 100%²; (5) 100%²; (6) 100%²
Yuan et al[51], 2013	Rat (n = 26)	L4-L5 (p)	(1) DBX + PBS; (2) DBX + NELL-1 (10μg); (3) DBX + NELL-1 (50μg); (4) Acellular collagen sponge (ACS) + PBS; (5) ACS + BMP-2; (6) ICBG	(1) 20%; (2) 100%; (3) 100%; (4) 0%; (5) 100%; (6) 0%
James et al[20], 2017	Macaque (n = 12)	L3-L4 L5-L6 (a)	(1) Cage + aTCP; (2) Cage + DBX + rh-NELL-1-loaded aTCP (1mg/mL); (3) Cage + DBX + rh-NELL-1-loaded aTCP (1.7mg/mL)	(1) 25%; (2) 25%; (3) 100%
Noggin
Klineberg et al[52], 2014	Rabbit (n = 25)	L5-L6 (p)	(1) ICBG + Noggin scrambled siRNA bilateral; (2) ICBG + scrambled siRNA one side + siRNA other side; (3) ICBG + functional siRNA bilateral	(1) - (2) - (3) 50%
P-15
Sherman et al[53], 2010	Sheep (n = 12)	L3-L5 (a)	(1) PEEK + ICBG; (2) PEEK + anorganic bovine-derived matrix/P-15	(1) 83%; (2)100%
Peptide B2A
Smucker et al[54], 2008	Rabbit (n = 45)	L4-L5 (p)	(1) ICBG; (2) ICBG + TCP (1:1); (3) ICBG + B2A (50 μg); (4) ICBG + B2A (100 μg); (5) ICBG + B2A (300 μg)	(1) 25%; (2) 22%; (3) 56%; (4) 78%² (vs A and B); (5) 40%
Cunningham et al[55], 2009	Sheep (n = 40)	L2-L3 L4-L5 (a)	(1) PEEK + ICBG; (2) PEEK + ICBG + B2A (50 μg); (3) PEEK + ICBG + B2A (100 μg); (4) PEEK + ICBG + B2A (300 μg); (5) PEEK + ICBG + B2A (600 μg)	(1) 63%; (2) 88%; (3) 88%; (4) 88%; (5) 75%
SPP24
Sintuu et al[56], 2011	Rat		(1) Collagen sponge (Sponge); (2) Sponge + rhBMP-2; (3) Sponge + rhBMP-2 (1 μg) + SPP24 (100 μg); (4) Sponge + rhBMP-2 (1 μg) + SPP24 (500 μg); (5) Sponge + rhBMP-2 (1 μg) + SPP24 (1 mg); (6) Sponge + rhBMP-2 (1 μg) + SPP24 (2.5 mg); (7) Sponge + rhBMP-2 (1 μg) + SPP18 (100 μg); (8) Sponge + rhBMP-2 (1 μg) + SPP18 (500 μg); (9) Sponge + rhBMP-2 (1 μg) + SPP18 (1 mg); (10) Sponge + rhBMP-2 (1 μg) + SPP18 (2.5 mg); (11) Sponge + rhBMP-2 (10 μg) + SPP24 (100 μg); (12) Sponge + rhBMP-2 (10 μg) + SPP24 (500 μg); (13) Sponge + rhBMP-2 (10 μg) + SPP24 (1 mg); (14) Sponge + rhBMP-2 (10 μg) + SPP24 (2.5 mg); (15) Sponge + rhBMP-2 (10 μg) + SPP18 (100 μg); (16) Sponge + rhBMP-2 (10 μg) + SPP18 (500 μg); (17) Sponge + rhBMP-2 (10 μg) + SPP18 (1 mg); (18) Sponge + rhBMP-2 (10 μg) + SPP18 (2.5 mg)	(1) 0%; (2) 100%²; (3) 0%; (4) 0%; (5) 0%; (6) 0%; (7) 0%; (8) 0%; (9) 0%; (10) 0%; (11) 0%; (12) 0%; (13) 0%; (14) 0%; (15) 0%; (16) 0%; (17) 0%; (18) 0%

¹(a/p): anterior/posterolateral surgical approach; N²: Statistically significant compared to all other experimental groups. ICBG: Iliac crest bone graft. BCP: Biphasic calcium phosphate; rhBMP-2: Recombinant human bone morphogenetic protein 2; bFGF: Basic fibroblast growth factor; GDF-5: Growth differentiation factor 5; PDLLA: Poly-D, L-lactide; TGF: Transforming growth factor; IGF: Insulin-like growth factor.

Citation: Cottrill E, Ahmed AK, Lessing N, Pennington Z, Ishida W, Perdomo-Pantoja A, Lo SF, Howell E, Holmes C, Goodwin CR, Theodore N, Sciubba DM, Witham TF. Investigational growth factors utilized in animal models of spinal fusion: Systematic review. World J Orthop 2019; 10(4): 176-191
URL: https://www.wjgnet.com/2218-5836/full/v10/i4/176.htm
DOI: https://dx.doi.org/10.5312/wjo.v10.i4.176