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. 2022 Jun 30;10:889481. doi: 10.3389/fbioe.2022.889481

TABLE 2.

Preclinical studies using Dextran and/or Pullulan scaffold in ectopic sites.

Author (Year) Animal model (sex; species); n, number of animals used Implantation site, dimension of the implanted material Conditions (N, number of total implanted materials per condition) Observation time [in day (D), week (W) or month (M)] Experimental analysis Results
Maire et al. (2005b) Rat (male, Sprague Dawley), n = 21 Muscle implantation (back) 1: BMP (N = 20) 7 W 2D X-ray (qualitative analysis) Dextran (DS 18%) + BMP showed large radiopaque areas compared to other groups (no statistical significance due to heterogeneity within the same group)
2: Dextran (DS 0%) + BMP (N = 14)
Collagen sponge Diameter: 7 mm Height: 7 mm 3: Dextran (DS 2%) + BMP (N = 14) Stevenel blue and Van Gieson Picrofuschin staining (Bone formation); Von Kossa staining (qualitative analysis) For Dextran (DS 18%) + BMP group, bone formation occurred through endochondral ossification or by intramembranous ossification
4: Dextran (DS 18%) + BMP (N = 14)
Degat et al. (2007) Rat (male, Sprague Dawley), n = 24 Subcutaneous (back) 1: BMP-2 (N = 6) 4 W Calcium mass (µg/implant) Dextran (10 µg) + BMP-2 ** > BMP-2
2: Dextran (1 µg) + BMP-2 (N = 6)
Collagen sponge 3: Dextran (10 µg) + BMP-2 (N = 6) BMP-2 * > Dextran (100 µg) + BMP-2
Diameter: 3 mm Height: 2 mm 4: Dextran (100 µg) + BMP-2 (N = 6)
Chen et al. (2019) Mouse (male, C57BL/6), n = 3 Muscle implantation (leg) 1: BMP-2 (N=NS) 2 W Wet and ash weights of ectopic bone (g) No significant difference observed between Dextran + BMP-2 and BMP-2 alone groups
Gelatin sponge size 2: Chitosan + BMP-2 (N=NS)
Length: 0.5 cm 3: Dextran + BMP-2 (N=NS)
Width: 0.5 cm 4: PSS + BMP-2 (N=NS) 4 W Masson’s Trichrome staining (qualitative analysis) Dextran + BMP-2 less bone formation compared to other groups
Height: 0.3 cm
Yu et al. (2020) Mouse (male, C56BL/6), n = 40 Muscle implantation (leg) 1: BMP-2 (10 µg) (N = 16) 2 W Micro-CT (BVF in %) No significant difference between groups
2: BMP-2 (15 µg) (N = 16)
Gelatin sponge size: NS 3: Heparin + BMP-2 (N = 16)
4: Chitosan + BMP-2 (N = 16) 4 W Masson’s Trichrome staining; TRAP+ staining (qualitative analysis) At 4W: for Dextran + BMP-2 group, traces of trabecular bone and bone resorption occurred
5: Dextran + BMP-2 (N = 16)
Hayashi et al. (2009) Mouse (male, ICR), n = NS Muscle implantation (leg) 1: Pullulan (N = 3–4) 3 W Micro-CT (BV in mm3) No significant difference between Pullulan and Pullulan + BMP-2 group
Diameter: 2.5 mm 2: Pullulan + BMP-2 (2 µg) (N = 3–4)
Height: NS
Fricain et al. (2013) Mouse (NS, Balb/c), n = NS Subcutaneous (back) 1: Pullulan/Dextran (N = 6) 15 D Micro-CT (MC in mg; MD in mg/cm3) Pullulan/Dextran + HA ** > Pullulan/Dextran
Diameter: 4 mm 2: Pullulan/Dextran + HA (N = 6) 30 D
Height: 4 mm 60 D Enzyme Immunoassay for BMP-2 (pg/mg protein) Pullulan/Dextran + HA * > Pullulan/Dextran
Goat (NS) n = 7 Muscle implantation (back) 1: Pullulan/Dextran (N = 12) 1 M Micro-CT (qualitative analysis) Osteoid tissue formation for Pullulan/Dextran + HA group
Diameter: 10 mm 2: Pullulan/Dextran + HA (N = 12) 6 M Von Kossa staining; Masson’s Trichrome staining (qualitative analysis) Osteoid tissue formation for Pullulan/Dextran + HA group
Depth: 10 mm

BMP, bone morphogenetic protein; BV, bone volume; BVF, bone volume fraction; D.S., degree of substitution; HA, hydroxyapatite; MC, mineral content; MD, mineral density; NS, not specified; PSS, poly (sodium-p-styrenesulfonate); * p < 0.05; ** p < 0.01.