Table 1 Data extracted from included papers in the systematic review
References | Type of scaffolds | Stem cells number/density | Animal species | Number of animals | Bone defect model and follow-up | Bone formation measurement | Scaffold + Cells (Mean ± SD (sample number)) | Scaffold-only control (Mean ± SD (sample number)) | Concluding remarks |
|---|---|---|---|---|---|---|---|---|---|
Annibali [19] | GDPB (Bio-Oss) with collagen and ß-TCP | 1 × 106 DPSC/defect (scaffold) | NIH-RNU FOXN1 nude rats | 8 | Critical Size Cranial defect, 12 weeks | Bone mineral density, BMD (mg/cm3) | 396.93 ± 298.39 (8) | 333.38 ± 119.5 (4) | GDPB induces a greater percentage of bone formation as compared to ß-TCP |
Annibali [20] | a) GDPB (Bio-Oss) with collagen | 1 × 106 DPSC/defect (scaffold) | Fox Chase SCID Beige mice | 75 | Critical Size Cranial defect, 8 weeks | % BV/TV | 17.75 ± 4.8 (4) | 21.31 ± 12.95 (3) | Bone regeneration is not significantly increased by DPSCs |
b) ß-TCP | 12.5 ± 5.7 (6) | 26.52 ± 9.9 (5) | |||||||
c) Agarose/nano-hydroxyapatite | 7.29 ± 3.9 (3) | 20.08 ± 7.67 (5) | |||||||
Ansari [21] | Alginate hydrogel with Cacl2 | 4 × 106 SHED/defect (scaffold) | C57BL/6 wild mice or Beige nu/nu XIDIII mice | 5 | Subcutaneous implantation, 8 weeks | % BV/TV | 62.8 ± 6.3 (5) | 4.2 ± 1.4 (5) | Encapsulated SHED in alginate 100 generated the largest amount of bone formation, while cell-free alginate failed to generate any bone (p < 0.05) |
Asutay [22] | HA/TCP | DPSC (number not reported) | Albino Wistar rats | 15 | Calvarial defect, 8 weeks | BMD (mg/cm3) | 0.40 ± 0.07 (10) | 0.24 ± 0.03 (10) | DPSC-loaded-HA/TCP scaffolds demonstrated the potential to benefit of healing process |
Bakopoulou [23] | Biomimetic chitosan/gelatin | DPSC (number not reported) | M/SOPF CB17/SCID mice | 6 | Subcutaneous implantation, 10 weeks | % bone formation | 19.77 ± 0.69 (6) | 10.3 ± 0.84 (6) | Densely nucleated, nanocrystalline mineralised was greater in the scaffold + DPSC group |
Behnia [24] | Cylindrical collagen sponge | SHED (number not reported) | Dog (Iranian mixed breed) | 4 | Mandibular defect, 12 weeks | % bone formation | 75.88 ± 13.12 (4) | 45.39 ± 17.91 (4) | SHEDs were capable of proliferation and osteogenesis after 5 years of cryopreservation |
Bressan [25] | Hydroxyapatite | 1 × 107/ml SHED | Wistar-NIH-FOXN1, nude rat | 24 | Calvarial defect, 3 weeks | Osteogenic marker expression | Not available | Not available | DPSCs of all donor ages are a potent tool for bone tissue regeneration when mixed with 3D nanostructured scaffolds |
Campos [26] | HA and P2O5-CaO-based glass (synthetic bone graft) | 1 × 105 DPSC/defect (scaffold) | Merino sheep | 12 | Mid-diaphysial defect, 120 days | % bone formation | 77.5 ± 9.5 (4) | 67.8 ± 11.2 (12) | The study proposes bone-like VR and DPSC combination as an efficient binomial strategy |
Colorado [27] | Polylactide-co-glycolide/hydroxyapatite (PLGA/HA) | 1 × 106 DPSC/defect (scaffold) | Wistar SPF rats | 20 | Calvarial defect, 10 weeks | New bone formation (mm2) | 1017.48 ± 24.47 (5) | 975.52 ± 35.46 (5) | PLGA/HA scaffolds containing hDPSCs displayed a significant increase in osteoid and mineralised tissue areas, which were superior to that obtained with PLGA/HA scaffolds alone |
Colpak [28] | DBBG (deproteinised bovine bone graft) + collagen | 2 × 106 DPSC/defect (scaffold) | Healthy sheep | 6 | Bilateral Iliac defect, 6 weeks | % bone formation | 29.00 ± 1.07 (16) | 18.45 ± 0.33 (16) | Bone graft and DPMSCs application with dental implant have beneficial effects on newly formed bone and vertical bone height |
da Silva [29] | Biphasic calcium phosphate (HA + ß-TCP) | 5 × 104 SHED/scaffold initial plating density, cultured for 7 days, then transplanted into the defect | Wistar rats | 50 | Calvarial defect, 8 weeks | % bone formation | 54.38 ± 15.67 (5) | 20.1 ± 1.51 (5) | BCP incorporated into SHED cultures showed promising outcomes for the repair of rat calvarial defects |
Fahimipour [30] | Collagen-heparin-ß-TCP | 5 × 106 DPSC/defect (scaffold) | Fischer 344 rats | 15 | Subcutaneous implantation, 8 weeks | Osteogenic marker expression | Not available | Not available | The designed construct induced the ectopic bone formation |
Fang [31] | Collagen | 5 × 105 SHED/scaffold initial plating density, cultured for 7 days, then transplanted into the defect | Sprague–Dawley rats | 6 | Calvariae cranial defects, 8 weeks | New bone formation (mm2) | 4.684 ± 0.812 (2) | 2.545 ± 0.704 (2) | Collagen + DPSC provides feasibility for clinical trials of large-scale bone loss |
Fu [32] | Mineralised gelatin sponge | 1 × 106 DPSC/ml initial plating density, cultured for 7 days, then transplanted into the defect | Nude mice | 2 | Subcutaneous implantation, 7 weeks | Osteogenic marker expression | Not available | Not available | The combination of DPSCs and Gelatin sponge scaffold has a great potential for bone tissue engineering |
Ghavimi [33] | Pluronic F68-containing aspirin-loaded PLGA nanoparticles | DPSC (number not reported) | Mongrel dogs | 6 | Alveolar defect, 4 weeks | New bone formation | Not available | Not available | The prepared membrane can be used as the GBR membrane for bone regeneration and antibacterial effect |
Gonçalves [34] | a) PLLA/collagen/HA | 1 × 106 SHED/scaffold initial plating density, cultured for 24 h, then transplanted into the defect | Wistar rats | 18 | Periodontal Fenestration defect, 30 days | New bone formation (mm2) | 0.27 ± 0.09 (6) | 0.28 ± 0.09 (6) | Both materials, even in the absence of stem cells, was able to promote bone and periodontal regeneration |
b) PisPLLA/collagen/HA | 0.22 ± 0.07 (6) | 0.28 ± 0.09 (6) | |||||||
Gutiérrez-Quintero [35] | Hydroxy apatite matrix and polylactic polyglycolic acid (HA/PLGA) | 5 × 105 DPSC/scaffold initial plating density, cultured for 24 h, then transplanted into the defect | New Zealand albino male rabbits | 8 | Mandibular critical-sized defects, 4 weeks | New bone formation (mm) | 5.59 ± 2.31 (8) | 3.15 ± 1.75 (8) | DPSCs seem to provide osteogenic properties showing significant results in bone regeneration compared with HA/PLGA scaffold |
Hiraki [36] | Atelocollagen | 1 × 105 SHED/defect (scaffold) | BALB/c-nu mice | 18 | Calvarial defect, 6 weeks | bone volume (mm3) | 5.152 ± 1.77 (6) | 1.722 ± 0.73 (6) | Bone regeneration was enhanced in defects treated with stem cells compared to that in controls |
Huang [37] | HNTs/GelMA hydrogels: halloysite nanotubes (HNTs) + gelatin methacrylate | 2 × 105 DPSC/scaffold initial plating density, cultured for 24 h, then transplanted into the defect | Sprague − Dawley rats | 12 | Calvarial defect, 12 weeks | BMD (mg/cm3) | 377.15 ± 46.35 (2) | 94.4 ± 26.3 (2) | The HNT-incorporated hydrogel proved a promising alternative strategy for bone regeneration |
Jahanbin [38] | Collagen matrix | 1 × 106 DPSC/scaffold initial plating density, cultured for 24 h, then transplanted into the defect | Wistar rats | 60 | Maxillary alveolar defect, 8 weeks | % bone formation | 27.3 (11) | 58.3 (12) | Stem cells plus scaffold have regenerative potential for repairing maxillary alveolar defects |
Jin [39] | Puramatrix (Synthetic peptide hydrogel) | 1 × 106/ml DPSC | Rats | 15 | Mandibular bone defect, 6 weeks | % BV/TV | 26.17 ± 3.6 (5) | 9.62 ± 2.94 (5) | Regenerated bone area of the DPSC + scaffold group was significantly higher than those in the control group |
Kang [40] | HA-TCPs, demineralised dentin matrix (DDM) | 1 × 106 DPSC/defect (scaffold) | Nude (athymic) mice | 20 | Subcutaneous implantation, 8 weeks | Bone volume change (mm3) | 1.2 ± 1.4 (5) | − 0.819 (5) | Both HA-TCP and DDM induced in vitro osteogenic differentiation potential of hDPSCs transplanted, and they enhanced ectopic bone tissue formation |
Kawanabe [41] | ß-TCP | 2 × 106 DPSC/defect (scaffold) | Fox Chase SCID mice | N/A | Subcutaneous implantation, 8 weeks | Osteogenic marker expression | Not available | Not available | Transplanted βTCP scaffolds and the specific cell surface antigen, SSEA-4 + DPSC generated a bone-like structure |
Kunwong [42] | PLGA-10% bioactive glass | SHED (number not reported) | Sprague–Dawley rats | N/A | Cleft mimicking model, 180 days | Osteogenic marker expression | Not available | Not available | SHED-PLGA-10% bioactive glass transplantation group showed more bone matrix than PLGA-10% bioactive glass without cells |
Kuo [43] | a) Calcium sulphate dehydrate (CSD) | 2 × 106/ml DPSC | Lanyu swine | 12 | Mandibular bone defect, 8 weeks | % bone formation | 69.7 ± 4.9 (3) | 33.9 ± 9.9 (3) | Mixing hDPSCs into the pure CSD showed effective improvement in new bone regeneration comparing to α-CSH/ACP or CSD/β-TCP |
b) α-calcium sulphate hemihydrate/amorphous calcium phosphate (α-CSH/ACP) | 70.5 ± 6.6 (3) | 61.7 ± 2.3 (3) | |||||||
c) CSD/β tricalcium phosphates (β-TCP) | 57.1 ± 4.1 (3) | 44.5 ± 2.9 (3) | |||||||
Kwon [44] | PLGC co-polymer scaffold: (MPEG-(PLLA-co-PGA-co-PCL) (PLGC)) | 1 × 106 DPSC/defect (scaffold) | Sprague–Dawley rats | 30 | Cranial defect, 12 weeks | % bone formation | 53 ± 6.7 (5) | 6 ± 2.1 (5) | The defect area in the PLGC scaffold/hDPSCs group was replaced by neo-bone tissues |
Liu [45] | HA + ß-TCP | 6 × 106 SHED/defect (scaffold) | C57BL/6 J mice and Beige nude/nude Xid (III) mice | N/A | Subcutaneous implantation, 8 weeks | % bone formation | Not applicable | Not applicable | Effect of Acetyl Salicylic Acid (ASA) only was analysed. When HA/TCP implanted with low doses of ASA (10/50 μg/mL) treatment, SHED-mediated new bone regeneration was increased |
Man [46] | 3D silk fibroin | DPSC (number not reported) | CD1 nude mice | N/A | Subcutaneous implantation, 6 weeks | Osteogenic marker expression | Not available | Not available | Selective HDAC2 and 3 inhibitor MI192 can promote hDPSCs osteogenic differentiation within lyophilised Bombyx Mori silk scaffolds |
Maraldi [47] | Collagen sponge | DPSC (number not reported) | CD® IG5 rats | 30 | Cranial defect, 8 weeks | % bone formation | 57.32 ± 3.99 (5) | 43.8 ± 7 (5) | Cell seeded group showed significantly higher mineralised tissue in the defect area than the cell-free group |
Mohanram [48] | Natural HA (anorganic bone mineral—ABM) | 5 × 106 DPSC/defect (scaffold) | MF1 Nu/Nu mice | 4 | Intraperitoneal chamber diffusion model, 8 weeks | Osteogenic marker expression | Not available | Not available | ABM-P-15 (collagen peptide) promoted HDPSCs osteogenic differentiation and bone matrix formation |
Nakajima [11] | PLGA membrane | SHED (number not reported) | BLAB/c-nu mice | 20 | Calvarial defect, 12 weeks | % BV/TV | 27.1 ± 12.13 (5) | 8.91 ± 6.5 (2) Empty ctrl | SHED may be one of the best cell source candidates for reconstructing an alveolar cleft |
Niu [49] | Intrafibrillar-silicified collagen scaffolds (ISCS) | 5 × 106 DPSC/ml initial plating density, cultured for 2 weeks, then transplanted into the defect | Nude mice | 6 | Subcutaneous implantation, 8 weeks | Osteogenic marker expression | Not available | Not available | Intrafibrillar-silicified collagen scaffolds significantly promoted the proliferation, osteogenic differentiation and mineralisation of hDPSCs, when compared with control |
Novais [50] | 3D Collagen | SHED (number not reported) | Athymic (nude) ‘NMRI-Foxn1 nu/nu’ mice | 45 | Calvarial defect, 90 days | % BV/TV | Not applicable | Not applicable | Effect of hypoxia and FGF2 only analysed and discussed and scaffold + cells were used as control. Priming SHED with FGF-2 in compressed collagen greatly enhanced regeneration |
Petridis [51] | Hydrogel scaffold (HyStem™-HP Cell Scaffold Kit, Sigma-Aldrich), composed by hyaluronic acid, heparin sulphate, gelatin and PEDGA solution | 1 × 106 DPSC/defect (scaffold) | Wistar rats | 30 | Calvarial defect, 8 weeks | % bone formation | 32.78 ± 9.24 (17) | 24.40 ± 8.29 (13) | The per cent of new bone formation in the cell–scaffold-treated group was significantly higher compared to scaffold treated groups |
Pisciotta [52] | Collagen sponge | 1 × 106 DPSC/scaffold initial plating density, cultured for 10 days, then transplanted into the defect | Sprague–Dawley rats | 10 | Cranial defect, 6 weeks | % bone formation | 69.15 ± 7.87 (4) | 39.15 ± 4.89 (4) | Stem cell–scaffold constructs, showed a significant contribution to the regeneration of critical size bone defect |
Prabha [53] | Polyvinyl alcohol (PVA)-Poly carbolactone (PCL)—hydroxyapatite-based (HAB) scaffold | 5 × 105 DPSC/defect (scaffold) | NOD.CB17‐Prkdcscid/J mice | 2 | Subcutaneous implantation, 8 weeks | Osteogenic marker expression | Not available | Not available | PVA-PCL-HAB scaffold supported the growth and attachment of DPSCs and in vivo vascularised bone formation |
Prahasanti [54] | Carbonate apatite scaffold (CAS) + gelatin | 1 × 106 SHED/defect (scaffold) | Wistar rats | 14 | Alveolar defect, 1 week | Osteogenic marker expression | Not available | Not available | SHED-incorporated CAS can enhance BMP-2 and BMP-7 expression while attenuating MMP-8 expression |
Prahasanti [55] | Hydroxyapatite | 1 × 106 SHED/defect (scaffold) | Wistar rats | 14 | Alveolar defect, 8 weeks | Osteogenic marker expression | Not available | Not available | Hydroxyapatite scaffold and SHED increase osteoprotegerin expression |
Saha [56] | Self-assembling β-peptides (SAPs), P11-4 | 5 × 104 DPSC/defect (scaffold) | Athymic rats | 20 | Calvarial defect, 6 weeks | BMD (mg/cm3) | 871 ± 34.2 (6) | 920 ± 71.4 (4) | Repair of the defect was not enhanced by the addition of hDPSCs with P11-4 |
Salgado [57] | Collagen–nanohydroxy apatite–phophoserine | 3 × 105 DPSC/scaffold initial plating density, cultured for 24 h, then transplanted into the defect | Nude mice | 4 | Subcutaneous implantation, 8 weeks | % bone formation | 46.97 ± 3.51 (4) | 43.21 ± 3.26 (4) | DPSC enhanced the percentage of the bone formation, but not statistically different to the control |
Saskianti [13] | HAS (biohydrox hydroxyapatite) | 1 × 106 SHED/defect (scaffold) | Wistar rats | 10 | Alveolar defect, 1 week | Osteogenic marker expression | Not available | Not available | The expression of VEGF increases significantly and MMP8 expression decreases with treatment of SHED seeded in HAS |
Saskianti [58] | Carbonate apatite | 1 × 106 SHED/ml initial plating density, cultured for 3 days, then transplanted into the defect | Rats (Rattus norvegicus) | 8 | Alveolar defect, 3 weeks | Osteogenic marker expression | Not available | Not available | The transplantation of SHED and carbonate apatite increased BMP4 expression as an indicator of osteogenic differentiation |
Seo [59] | HA + TCP | 2 × 106 SHED/defect (scaffold) | NIH-bg-nu-xid, Harlan Sprague–Dawley mice | 18 | Calvarial defect 8 weeks | % bone formation | 33.7 ± 6.3 (6) | 1.24 ± 0.1 (6) | SHED may select unique mechanisms to exert osteogenesis |
Serano-Bello [60] | Hydroxyapatite–microporous alginate sponges (MAS) | DPSC (number not reported) | Wistar rats | 24 | Calvarial defect, 90 days | % bone formation | 90 ± 5.88 (6) | 3.43 ± 0.35 (6), Empty ctrl | MAS with 30% HA, the total volume of the regenerated area was statistically significant with regard to the control and other groups |
Vater [61] | Mineralised collagen Matrix (MCM) | 5 × 104 DPSC/scaffold initial plating density, cultured for 24 h, then transplanted into the defect | NMRI nude mice | 36 | Critical mid-diaphyseal defect, 6 weeks | BMD (mg/cm3) | 825.5 ± 64 (12) | 849.8 ± 43.94 (11) | Pre-seeding of MCM scaffolds with DPSCs did not enhance bone defect healing when compared with the cell-free MCM control |
Wongsupa [62] | poly(ε-caprolactone)-biphasic calcium phosphate construct (PCL/BCP) | DPSC (number not reported) | New Zealand white rabbits | 18 | Calvarial defect, 8 weeks | % BV/TV | 25.33 ± 0.75 (3) | 13.28 ± 2.41 (3) | hDPSCs combined with PCL/BCP scaffolds may be an augmentation material for bony defect |
Xavier Acasigua [63] | poly (lactic-co-glycolic acid) (PLGA) | 5 × 104 SHED/scaffold initial plating density, cultured for 14 days, then transplanted into the defect | Wistar rats | 20 | Calvarial defect, 60 days | % bone formation | 17 ± 4.31 (5) | 9.39 ± 2.55 (5) | PLGA associated with SHED can promote bone formation |
Zhang [64] | Tyrosine-derived polycarbonate, E1001(1 K)/ß-TCP | 2.5 × 104 DPSC/mm3 initial plating density, cultured for 7 days, then transplanted into the defect | New Zealand White rabbits | 10 | Mandibular defect, 90 days | BMD (mg/cm3) | 0.51 ± 0.1 (3) | 0.40 ± 0.1 (2) | Vascularised craniofacial bone was regenerated using hDPSCs combined with the scaffolds |
Zhu [65] | Bio-Oss—Collagen | 2 × 107 DPSC/ml initial plating density, cultured for 7 days, then transplanted into the defect | Nude mice | 36 | Calvarial defect, 8 weeks | % BV/TV | 56.42 ± 2.62 (9) | 47.36 ± 2.41 (9) | It was hypothesised that DPSCs implanted scaffold would promote bone healing in bone defect |