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. 2020 May 14;8:430. doi: 10.3389/fbioe.2020.00430

Table 2.

Study results.

Paper Evidence of osteogenesis (micro-CT) Evidence of angiogenesis
Immunohistochemistry results Microfil® perfusion results
Jing et al. (2018) 12W: in the group using 45S5 Bioglass scaffold alone, new bone was created and partially repaired the bone defect. This was compared to the negative control in which minimal bone was created 12W: CD31 and VEGF staining: number of both CD31 and VEGF-positive microvessels were significantly higher with 45S5 bioactive glass scaffold treated defects compared to the negative control experiments (p < 0.05)
Wang et al. (2019) 12W: New bone formation was seen in all groups however this was markedly increased in groups treated with bioactive glass scaffolds treated more graphene oxide:
Bone mineral density: MBG-HGO showed significantly greater BMD (0.64 ± 0.08 g/cm3) than MBG group (0.10 ± 0.04 g/cm3) and MBG-LGO group (0.50 ± 0.04 g/cm3) (p < 0.05). MBG-LGO showed significantly greater bone mineral density than the MBG group (p < 0.05)
Bone volume fraction: MBG-HGO showed significantly greater bone volume/total volume than MBG group and MBG-LGO group (p < 0.05). MBG-LGO showed significantly greater bone volume/total volume than MBG group (p < 0.05)
4W: CD34 staining: showed very little staining with pure bioactive glass scaffolds, however, staining was very strong in bioactive glass scaffolds treated with graphene oxide 12W: Microfil®
perfusion experiments: showed that there were higher levels of new vascularization with graphene oxide treated bioactive glass scaffolds
Wu et al. (2019) 8W: Bone mineral density and bone volume fraction: In comparison to gels without bioactive glass, gels with bioactive glass showed significantly increased levels of osteogenesis as measured by BMD and bone volume fraction. Adding copper to the bioactive glass-silk fibroin-chitosan composite further increased levels of osteogenesis, showing full repair of the defect Cu-BG/CH/SF/GP(II) gel had highest BMD and BV/TV 8W: α smooth muscle (α-SMA) antigen staining: slight staining present in both bioactive glass containing group (BG/CH/SF/GP) and non-bioactive glass containing group (CH/SF/GP). Copper treated bioactive glass containing groups Cu-BG/CH/SF/GP (I) and Cu-BG/CH/SF/GP (II) gel showed significantly more staining than those without copper (BG/CH/SF/GP and CH/SF/GP)
Min et al. (2015) 8W: markedly increased bone growth was observed in defects treated with bioactive glass scaffolds (+/–DMOG loading) compared to controls treated without an implant 8W: Microfil® perfusion experiments: showed new vascularization in the bone defects implanted with bioactive glass scaffolds (+/–DMOG loading). DMOG loaded bioactive glass scaffolds showed more ingrowth of dense vessels into the of the defect compared to DMOG-unloaded bioactive glass scaffolds, which promoted growth around the periphery
Xin et al. (2017) 4W and 8W: volume of new bone and volume of mature bone in bioactive glass containing scaffold groups (GelMA/MBGNs and GelMA-G-MBGNs) was significantly more than in non-bioactive glass containing scaffold groups (GelMA and control groups)
Bone volume fraction: GelMA-G-MBGNs > GelMA/MBGNs > GelMA.
4W: CD31 staining: GelMA-G-MBGNs group > GelMA/MBGNs group > GelMA group > control group when measured at same time interval after implantation (p < 0.05)
Qi et al. (2017) 8W: PHMBD > PHMB> PHMD > PHMG and PHMD groups in order of osteogenesis
Bone mineral density: BMD was greatest for the PHMBD group (0.876 ± 0.021g/cm3), which was significantly greater than the PHMG, PHMB and PHMD groups. PHMB group had significantly greater BMD than both PHMG and PHMD groups
CD31 staining: greater in PHMD and PHMBD than PHMB and PHMG groups 8W: Microfil® perfusion experiments: New blood vessel areas: PHMBD (86.09 ± 3.989%) > PHMD (36.11 ± 3.687%) >PHMB (21.648 ± 2.459%) >PHMG groups (1.265 ± 0.415%) (all p < 0.05) PHMBD group had the greatest area of neovascularization of defects forming microvessels and good connectivity between vessels. Neovascularization was observed in PMBD and PHMD groups but less in PHMB group and the least in PHMG
Li et al. (2019) 8W: New bone volume: FTY/MBG-PLGA (9.15 ± 1.2%, p < 0.05) > MBG-PLGA (9.15 ± 1.2%, p < 0.05) > PLGA group (all p < 0.05). No difference between PLGA and controls
Bone volume fraction: FTY/MBG-PLGA > MBG-PLGA (p < 0.05) FTY/MBG-PLGA > PLGA (p < 0.01) FTY/MBG-PLGA> neg control (p < 0.001) MBG-PLGA> PLGA (p < 0.05) MBG-PLGA> neg control (p < 0.01)
CD31 staining: FTY/MBG-PLGA > MBG-PLGA (p < 0.05) FTY/MBG-PLGA > PLGA (p < 0.01) FTY/MBG-PLGA> neg control (p < 0.01) MBG-PLGA> PLGA (p < 0.05) MBG-PLGA> neg control (p < 0.05) 8W: Microfil® perfusion experiments: New blood vessel areas: FTY/MBG-PLGA (21.07 ± 2.02%) > MBG-PLGA group (10.25 ± 1.26%) > PLGA (4.10 ± 0.84%) -all p < 0.05 FTY/MBG-PLGA had greatest area of neovascularization
Jia et al. (2015) 3M and 9M: new bone formation: Both silicate 13–93 and borosilicate 2B6Sr showed significantly more new bone formation compared to the negative control
9M: complete bone healing in both silicate 13–93 and borosilicate 2B6Sr groups compared to negative control where a gap in defect was observed
CD31 staining:
3M: 2B6Sr glass scaffold >13–93 glass scaffold and ABG group (P < 0.05)
9M: no difference between 2B6Sr glass scaffold, 13–93 glass scaffold and ABG groups Increased blood vessels observed from 3M to 9M in 2B6Sr glass scaffold >13–93 glass scaffold and ABG group
Zhao et al. (2015) 8W: bone mineral density: Sr-MBG scaffolds group (503.30 ± 88.93 mg cm−3) > MBG group (339.30 ± 36.61 mg cm−3) > negative control group (58.67 ± 20.65 mg cm−3) (all p < 0.05)
Bone volume fraction: Sr-MBG scaffolds group (31.33 ± 4.93%) > MBG scaffolds group (17.67 ± 5.03%) > negative control group (4.33 ± 1.52%) (all p < 0.05)
8W: Microfil® perfusion experiments: New blood vessel areas and vessel number: Sr-MBG scaffold > MBG scaffold > negative control (all p < 0.05)

Summary table detailing author names, publication date, evidence of osteogenesis measured using micro-CT and evidence of angiogenesis, measured using Microfil® perfusion and immunohistochemistry, after implantation of bioactive glass scaffolds into animal models.

45S5, glass with 45 wt.% of SiO2 and 5:1 molar ratio of Calcium to Phosphorus; ABG, autologous bone graft; BMP-2, human bone morphogenetic protein-2; BV/TV, bone volume/total bone volume; CD31, cluster of differentiation 31; CD34, cluster of differentiation 34; Cu-BG/CH/SF/GP(II), copper-doped bioactive glass with chitosan (CH)/silk fibroin (SF)/glycerophosphate (GP) concentration 2; Cu-BG/CH/SF/GP, copper-doped bioactive glass with chitosan (CH)/silk fibroin (SF)/glycerophosphate (GP) concentration 1; DMOG, dimethyloxallyl glycine; FTY720, fingolimod; GelMA-G-MBGNs, mesoporous bioactive glass nanoparticles (MBGNs) with photo-cross-linkable GelMA which have been further integrated into GelMA; GelMA, gelatin derivative containing gelatin+ methacrylicanhydride; M, months; MBG-LGO, mesoporous bioactive glass- low graphene oxide; MBG- PHBHHx, (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); MBG-HGO, mesoporous bioactive glass- high graphene oxide; MBG, mesoporous bioactive glasses; PHMB, BMP-2 + MBG-PHBHHx; PHMBD; BMP-2 + DMOG + MBG-PHBHHx; PHMD, DMOG + MBG-PHBHHx; PHMG, pure MBG-PHBHHx; VEGF, vascular endothelial growth factor; W, weeks. The bold values display the timing when each result was measured, and which method was used to do this.