Table 1.
Pre-clinical experiments of MSCs-combined with biomaterial for bone regeneration in large animal bone defect models.
| Author | Experiment Animal | Type and Size of Defect | Experimental Transplant Groups | Post-Transplant Follow up Period |
Outcome |
|---|---|---|---|---|---|
| Probst et al., 2020 [50] | Mini pigs | Critical mandibular defect (3 × 1 × 2 cm) | 3D TCP-PLGA scaffold seeded with osteogenic differentiated Porcine ADSCs (pADSCs). | 12 weeks | pADSCs seeded TCP-PLGA scaffold constructs significantly improved bone regenerations compared to empty scaffold. |
| Wang et al., 2019 [64] | Rhesus Monkeys | Critical alveolar bone defect (10 × 10 × 5 mm) | 3D-Bioactive glass (BG) + BMP/chitosan (CS) + BMMSCs | 12 weeks | BMP/CS nanoparticles loaded on 3D-BG scaffold promoted bone regeneration ability in vivo, and preload of BMMSCs promote this ability further. |
| Hsieh et al., 2019 [65] | domestic Ds-Red pigs | Calvarias defect (8 mm in diameter and 2 mm in depth) | Hemostatic gelatin sponge scaffold seeded with EGFP pig BMMSCs | 1, 2, 3 and 4 weeks | Osteoid formation in the scaffolds transplanted with seeded BMMSCs was significantly higher than the control group. |
| Shi et al., 2019 [66] | Minipigs | Maxillary Intraosseous circular defects (12 mm in diameter and 5 mm in depth) | Bio-Oss/autogenous (Pig Gingival MSCs) pGMSCs (2 × 106)/SB431542 (TGF-β signalling inhibitor). | 8 weeks | pGMSCs treated with a TGF- β signaling inhibitor successfully repair minipig severe maxillofacial bone defects. |
| Qiu et al., 2018 [67] | Minipigs | Lateral femoral condyle defect (8 mm in diameter and 10 mm in depth) | Calcium phosphate cement (CPC) scaffold seeded with autologous BMMSCs plus autologous PRP (CPC-BMSC-PRP, 1 × 106 cells/scaffold) | 6 and 12 weeks | CPC scaffold co-delivered BMMSCs-PRP promoted scaffold resorption and doubled bone regeneration in large defects than control groups |
| Zhang et al., 2017 [68] | Minipigs | Non-healing full thickness cranial defects (2 cm width × 3 cm length × 0.5 cm depth) | IMC (intrafibrillarly-mineralized collagen) scaffold seeded with 1 × 106 PDLSCs cells | 12 weeks | Compared with HA, IMC-seeded PDLSCs achieved a significantly higher extent of new bone formation, with the normal architecture of natural bones and blood vessels. |
| Scarano et al., 2017 [69] | Minipigs | Critical-size circular defects (5 mm diameter; 5 mm thickness) in the mandibular body | Bone porcine block (BPB) scaffold seeded with 100 ul cell suspension of BMMSCs | 12 weeks | BPB when used as a scaffold induce bone regeneration and further benefit from the addition of BMMSCs in the tissue-engineered constructs. |
| Lin et al., 2015 [70] | Minipigs | Massive segmental bone defects (30 mm in length) at the mid-diaphysis of femora | Transduced pig ADSCs loaded onto PLGA scaffold | 2, 4, 8 and 12 weeks | ADSCs/scaffold constructs successfully healed massive segmental bone defects at the mid-diaphysis of femora in minipigs significantly than control group. |
| Cao et al., 2015 [71] | Mini pigs | Calvarial bone defects (3 cm × 1.8 cm oval defect) | BMMSCs pretreated with 75 μg/mL aspirin for 24 h seeded onto hydroxyapatite/tricalcium phosphate (HA/TCP) | 6 months | BMMSCs pretreated with aspirin have a greater capacity to repair calvarial bone defects in a mini swine model |
| Fan et al., 2014 [72] | Rhesus monkeys | Segmental tibial defects (20 mm in length) | Autologous prevascularized BMMSCs (5 × 106)-β-TCP constructs | 4, 8 and 12 weeks |
Significantly higher amount of neo-vascularization and radiographic grading score in prevascularized BMMSCs-β-TCP constructs |