TABLE 3.
Preclinical studies using Dextran scaffolds for bone regeneration in orthotopic sites.
| Author (Year) | Animal model (sex; species); n, number of animals used | Type of defect (defect size) | Conditions (N, number of defects created in total per condition) | Observation time [in day (D), week (W) or month (M)] | Experimental analysis | Results |
|---|---|---|---|---|---|---|
| Lafont et al. (2004) | Rat (male, Wistar), n = 98 | Calvaria | 1: PBS (N = 49) | 1 D | 2D x-ray analysis (Bone Repair in %) | At 7D: Dextran *** > PBS |
| 2 D | ||||||
| 3 D | ||||||
| 4 D | ||||||
| Ø: 5 mm | 2: Dextran (N = 49) | 5 D | ||||
| 6 D | ||||||
| 7 D | Toluidine blue staining (ALP staining, qualitative analysis) | For Dextran group: at 5D, bone formation began at the edges of the defect and bone nodules appeared at 6D | ||||
| Chen et al. (2005) | Dog (female, Beagle), n = 12 | Periodontal class III furcation (2nd, 3rd and 4th premolars) H: 5 mm |
1: CPC covered by Simple Membrane (N = 33) | 8 W | HE staining (New bone area in %) | Dextran/Gelatin + BMP-2 ** > CPC |
| 2: CPC + BMP-2 covered by Simple Membrane (N = 32) | ||||||
| 3: Dextran/Gelatin + BMP-2 in CPC covered by Functionalized Membrane (N = 34) | ||||||
| Chen et al. (2006) | Dog (male, Beagle), n = 12 | Periodontal class III furcation (2nd and 3rd molars) | 1: Empty (N = 16) | 4 W | 2D X-Ray (qualitative analysis) | For Dextran/Gelatin containing IGF groups, new bone formation was observable |
| 2: Dextran (D.S. = 6.3)/Gelatin (N = 16) | ||||||
| 3: IGF-1 (N = 16) | ||||||
| H: 5 mm | 4: Dextran (D.S. = 4.7)/Gelatin + IGF-1 (N = 16) | 8 W | HE staining; Modified Mallory’s Trichrome staining (Morphometric analysis of new bone in %) | Dextran (D.S. = 4.7)/Gelatin + IGF-1 * > Dextran (D.S. = 7.8)/Gelatin + IGF-1 | ||
| 5: Dextran (D.S. = 6.3)/Gelatin + IGF-1 (N = 16) | ||||||
| 6: Dextran (D.S. = 7.8)/Gelatin + IGF-1 (N = 16) | ||||||
| Chen et al. (2007) | Dog (male, Mongrel), n = 6 | Periodontal class III furcation (2nd and 3rd premolars) | 1: Dextran/Gelatin (N = 16) | 8 W | Modified Mallory’s Trichrome staining (Height of new bone regenerated in mm; % of regenerated new bone) | Dextran/Gelatin + microsphere BMP ** > Dextran/Gelatin + aqueous BMP * > Dextran/Gelatin |
| H: 5 mm | 2: Dextran/Gelatin + microsphere BMP (N = 16) | |||||
| 3: Dextran/Gelatin + aqueous BMP (N = 16) | ||||||
| Abbah et al. (2012) | Rat (male, Sprague Dawley), n = 38 | Arthrodesis (iliac bone L3, L4 fusion) | 1: Empty (N = 6) | 6 W | Micro-CT (BVF in %) | PLA + BMP-2 ** > DEAD-Dextran + BMP-2 |
| Bioresorbable mPCL-TCP scaffold | 2: Alginate + BMP-2 (N = 8) | |||||
| L: 4 mm | 3: PLO + BMP-2 (N = 8) | |||||
| W: 4 mm | 4: PLA + BMP-2 (N = 8) | |||||
| H: 4 mm | 5: DEAE-Dextran + BMP-2 (N = 8) | Masson’s Trichrome staining (qualitative analysis) | DEAD-Dextran: new bone tissue was thin and sparse | |||
| Bölgen et al. (2013) | Rat (NS, Sprague Dawley), n = 57 | Calvaria | 1: HEMA/Lactate/Dextran (N = 29) | 30 D | HE staining; | At 180D: HEMA/Lactate/Dextran > HEMA/Lactate/Dextran + MSCs * |
| Ø: 8 mm | 2: HEMA/Lactate/Dextran + MSCs (N = 28) | 90 D | Masson’s Trichrome staining (New bone/Total cavity ratio) | |||
| 180 D | ||||||
| Togami et al. (2014) | Rabbit (male, Japanese) n = 9 | Femoral (epiphysis) | 1: PVF/Dextran without water holding capability (N = 9) | 2 W | Micro-CT (BV/TV in %; BMD in mg/cm3) | At 4W and 6W: PVF/Dextran water holding capability ** > PVF/Dextran without water holding capability |
| Ø: 4 mm | 2: PVF/Dextran with water holding capability (N = 9) | 4 W | HE staining (Ratio of bone formation per area in %) | PVF/Dextran water holding capability > PVF/Dextran without water holding capability *** | ||
| H: 10 mm | 6 W | Newly trabecular bone with lamellar structures for PVF/Dextran water holding capability | ||||
| Ritz et al. (2018) | Mouse (NS, Athymic nude), n = 40 | Calvaria | 1: Empty (N = 2) | 8 W | Micro-CT (BV/TV in Voxel) | Dextran + HUVEC * > Empty |
| Ø: 2.7 mm | 2: Dextran (N = 16) | Dextran + SDF-1 * > Empty | ||||
| 3: Dextran + HUVEC (N = 16) | ||||||
| 4: Dextran + HUVEC/hOB (N = 14) | HE staining (qualitative analysis) | For Dextran + HUVEC or SDF-1 groups: fibrous membrane structure complemented by a thin bony structure covering the whole defect | ||||
| 5: Dextran + SDF-1 (N = 16) | ||||||
| 6: Dextran + BMP-7 (N = 16) | ||||||
| Ding et al. (2019) | Rat (NS, Sprague Dawley), n = 24 | Calvaria | 1: Chitosan/Dextran (N = 6) | Micro-CT (BV/TV in %) | Chitosan/Dextran + Sr100HA* > Chitosan/Dextran + HA * > Chitosan/Dextran | |
| 2: Chitosan/Dextran + HA (N = 6) | 4 W | |||||
| Ø: 5 mm | 3: Chitosan/Dextran + Sr50HA (N = 6) | 8 W | HE staining (New bone area fraction in %); Masson’s Trichrome staining (Regenerated collagen in %) | Chitosan/Dextran + Sr100HA * > Chitosan/Dextran | ||
| 4: Chitosan/Dextran + Sr100HA (N = 6) | ||||||
| Fang et al. (2019) | Rabbit (female, New Zealand), n = 18 | Femoral (condyle) | 1: Dextran/Polyacrylamide (N = 18) | 0 D | Micro-CT (BMC in mg; BV in mm3) | At 30D: HA-Dextran/Polyacrylamide ** > Dextran/Polyacrylamide |
| Ø: 3 mm | 2: Dextran/Polyacrylamide + HA (N = 18) | 30 D | ||||
| H: 5 mm | 90 D | HE staining; Masson’s Trichrome staining (qualitative analysis) | At 30D: HA-Dextran/Polyacrylamide groups sowed osteoid tissue formation which was not observed without HA | |||
| Shoji et al. (2020) | Mouse (NS, C57BL/6J), n = NS | Femur fracture | 1: Empty (N=NS) | 4 W | Micro-CT (BV in mm3; BMC in mg) | Dextran + bFGF * > Empty |
| L: 10 mm | 2: Dextran + PBS (N = 8) | |||||
| W: 4 mm | 3: Dextran + bFGF (N = 8) | HE staining (qualitative analysis) | Large calluses and newly formed bone at fracture site for Dextran + bFGF group | |||
| Wang et al. (2021) | Rats (female, Sprague Dawley) n = 18 | Calvaria | 1: Empty (N = 9) | 4 W | Micro-CT (BVF in %; BMD in g/cc; trabecular number in mm−1) | Dextran/PLGA + HA + BP * > Empty |
| Ø: 4 mm | 2: Dextran/PLGA + HA + BP (N = 9) | 8 W | ||||
| 12 W | HE staining; Toluidine blue staining (qualitative analysis) | At 8W: for Dextran/PLGA + HA + BP group, large area of woven bone and thin lamellar structure |
BMC, bone mineral content; BMD, bone mineral density; BMP, bone morphogenic protein; BP, bisphosphonate; BV, bone volume; BV/TV, bone volume over total volume; β-TCP, beta-tricalcium phosphate; BVF, bone volume fraction; CPC, calcium phosphate ceramic; DEAE, diethylaminoethyl; D.S., degree of substitution; H, height; HA, hydroxyapatite; HE, hematoxylin and eosin; HEMA, hydroxyethyl methacrylate; hOB, human osteoblast; HUVEC, human umbilical vein endothelial cells; L, length; MC, mineral content; MD, mineral density; Micro-CT, micro-computed tomography; mPCL-TCP, medical grade poly (ε-caprolactone)—β-tricalcium phosphate; MSCs, mesenchymal stromal cells; n/s not significant; NaCl, sodium chloride; PBS, phosphate buffer saline; PLA, poly-L-arginine; PLO, poly-L-ornithine; PVF, polyvinyl formol; Sr, strontium; W, width * p < 0.05; ** p < 0.01; *** p < 0.001; ø, diameter.