Table 1.
Authors and Year | Animal Model and Age | MSCs Type | Transduction/Transfection Method | BMP Therapy Delivery Method | Diameter Size of the Defect | Approximate Number of Cells Seeded | BMP Therapy | BMP Dose | Type of Scaffold Used to Seed MSCs | Endpoints |
---|---|---|---|---|---|---|---|---|---|---|
Aquino-Martinez, R. et al., 2016 [6] | Six to eight-week-old GFP transgenic BALB/c mice | BMSCs | Embedded in scaffold | Embedded in scaffold | 5 mm | 3.5 × 105 | BMP-2 | 2 nM | Gelatin/CaSO4 scaffold | 5 Weeks |
Chuang, C.K. et al., 2010 [7] | Female immunocompetent Sprague-Dawley rats. 10 weeks | BMSCs | Baculovirus | Transduction | 8 mm | 5 × 106 | BMP-2 | Not reported | PLGA | 4 and 12 weeks |
Du, M. et al., 2017 [8] | Seven to eight-week-old, adult female Wistar rats | BMSCs | Embedded in scaffold | Embedded in scaffold | 8 mm | 4 × 104 | BMP-2 | 800 ng/mL | Acellular dermal matrix membrane | 1 and 2 weeks |
Gao, X. et al., 2014 [9]. | Eight-week-old Male CD-1 nude mice | BMSCs | Lentivirus | Transduction | 5 mm | 1.5 × 106 | BMP-2 | Not reported | Fibrin sealant | 1, 14, 28 and 42 days |
Gao, X. et al., 2022 [10] | Seven-weeks-old ICRSCID mice at | hMDSCs | Embedded in scaffold | Embedded in scaffold | 5 mm | 2 × 104 | BMP-2, 4, 6, 7, 9 | 50 ng/mL | Fibrin sealant | 1, 14, 28 and 42 days |
Gohil, S. V. et al., 2016 [11] | Col3.6Cyan (ECFP) mice | BMSCs | Embedded in scaffold | Embedded in scaffold | 3.5 mm | 3 × 106 cells/cm2 | rhBMP-2 | 2 ug | Chitosan thermogel | 4 and 8 weeks |
He, X. et al., 2014 [12] | Male SD rats at 8 weeks of age | BMSCs | Embedded in scaffold | Embedded in scaffold | 8 mm | 1 × 106 | BMP-2 | 200 ng/mL | Chitosan/alginate/hydroxyapatite | 12 weeks |
Hsieh, M. K. et al., 2018 [13] | Eight-week-old Sprague-Dawley male rats | BMSCs | E. coli/TransIT-2020 | Transfection | 8 mm | 1 × 106/mL | BMP-2 | Not reported | Corning Matrigel basement membrane Matrix High Concentration | 12 weeks |
Jin, H. et al., 2014 [14] | Male Wistar rats | BMSCs | Cells in transfection media | Transfection | 5 mm | 2 × 105 | BMP-2 | Not reported | polyethylenimine–alginate (PEI–al) nanocomposite | 4 and 8 weeks |
Kong, Y. et al., 2019 [15] | Eight-week-old Sprague-Dawley rats | BMSCs | Embedded in scaffold | Embedded in scaffold | 5 mm | 5 × 105 | BMP-2 | 0.5 ± 0.02 μg/mL | Sodium alginate microcapsules and polylactic acid (PLLA) microspheres | 4 and 8 weeks |
Kuttappan, S. et al., 2018 [16] | Four to five-month-old male Wistar rats | ADSCs | Embedded in scaffold | Embedded in scaffold | 8 mm | 5 × 104 | BMP-2 | Not stated | Nanocomposite fibrous | 4 and 12 weeks |
Lee, J.H. et al., 2015 [17] | Male Sprague-Dawley rats | hADSCs | E. coli | Transfection | 8 mm | 2 × 103–2 × 104 | rhBMP-2 | Not reported | Collagen sponge | 2 and 6 weeks |
Li, L. et al., 2015 [18] | Female Sprague-Dawley rats | BMSCs | Embedded in scaffold | Embedded in scaffold | 8 mm | 2 × 104 | BMP-2 | 80 mg | Dexamethasone embedded PCE polymer | 4 and 12 weeks |
Park, S.H. et al., 2010 [19] | Male immunocompetent Sprague-Dawley rats. 6 weeks | BMSCs | rAd | Transduction | 8 mm | 5 × 105 | BMP-2 | Not reported | Matrigel matrix | 4 weeks |
Shao, N. et al., 2018 [20] | Six-week-old Sprague-Dawley (SD) male rats | BMSCs | Embedded in scaffold | Embedded in scaffold | 5 mm | 5 × 104 | BMP-2 | 340–400 μg | Inorganic hydroxyapatite gel | 12 weeks |
Stephan, S.J. et al., 2010 [21] | Six to eight-month-old Sprague-Dawley rats | BMSCs | Embedded in scaffold | Embedded in scaffold | 8 mm | 0.3 × 106 | BMP-2 | 2 μg | Chitosan gel | 4 and 8 weeks |
Strecker, S. E. et al., 2019 [22] | Osterix-mCherry mice | BMSCs | Embedded in scaffold | Embedded in scaffold | 4 mm | 1.2 × 106 cells/cm2 | rhBMP-2 | 0.2 μg | Dextran-Dendrimer Hydrogel Nanocomposite | 4 and 8 weeks |
Subbiah, R. et al., 2015 [23] | Seven-week-old SD rats | UCMSCs | Embedded in scaffold | Embedded in scaffold | 9 mm | 2.5 × 106 | BMP-2 | 392 ± 18 ng | PLGA NP and alginate microcapsules | 4 and 8 weeks |
Sun, K. et al., 2020 [24] | SCID mice. Age not specified | BMSCs | rAAV | Transduction | 5 mm | 1 × 107 | BMP-2 | Not reported | mGL hydrogel scaffold | 6 weeks |
Terella, A. et al., 2010 [25] | Albino male Sprague Dawley rats aged 10–11 weeks | Not specified | Embedded in scaffold | Embedded in scaffold | 8 mm | 1 × 107 | BMP-2 | 5–15 ng/80 uL | PEG-DA, and PEG-MMP | 1, 4 and 8 weeks |
Vila, O.F. et al., 2014 [26] | 10-week-old SCID mice | hADSCs | Lentivirus | Transduction | 3 mm | 0.2 × 106 | BMP-2 | Not reported | Fibrin matrix | 6 weeks |
Zhang, Y. et al., 2011 [27] | SCID mice. Age not specified | BMSCs | Adenovirus | Transduction | 3 mm | 1 × 106 | BMP-7 | Not reported | Silk fibroin | 4 weeks |
Zhou, C. et al., 2020 [28] | Two-week-old Sprague-Dawley rats | BMSCs | Lentivirus | Transduction | 5 mm | 2 × 106 cell/mL | BMP-9 | Not reported | P3HB4HB thermogel | 4 weeks |
Abbreviations: BMP: Bone morphogenic protein; CT-scan: Computerized tomography scan; mGL: Methacrylated gelatin; H&E: Hematoxylin and eosin staining; hBMSCs: Human bone marrow-derived stem cells; hADSCs: Human adipose-derived stem cells; hMdSCs; Human muscle derived stem cells; nTmGL group: mGL scaffold loaded with BMP-2 and hBMSCs; PLGA: Poly-Lactic-Glycolic-Acid; rAAD: Recombinant adeno-associated virus; PEG-DA: Poly (ethylene glycol)-diacrylate; PEG-MMP: Protease sensitive PEG; rAd: Recombinant adenovirus; SCID: Severe combined immunodeficient; TmGL group: mGL scaffold seeded with hBMSCs transduced with BMP-2; hMDSCs: Human muscle derived stem cells; PCE: Poly(ε-caprolactone)-poly(ethylene glycol); UCB-MSCs: Umbilical cord blood-derived mesenchymal stem cells; PLGA NPs: Poly(lactic-co-glycolic acid) nanoparticles; nHAp-BMP-2: Nano-hydroxyapatite peptide covalently immobilized with BMP-2.