Table 6.
Overview of the studies using the MSC secretome in combination with biomaterial for bone regeneration in in vivo models.
| Secretome | MSC Source | Biomaterial | Species | Model | Results | Ref. |
|---|---|---|---|---|---|---|
| CM or cytokine cocktail that mimics the CM | BMSCs | Atelocollagen sponge | Wistar/ST rats | Calvarial bone defects | Bones regenerated thanks to the recruitment of endogenous stem cells and endothelial cells | [110] |
| CM | MSCs | Atelocollagen | Wistar/ST rats | Calvarial bone defect model | New bone formation | [111] |
| CM | BMSCs | Col sponge | Sprague Dawley rats; BALB/C mice | Calvaria defect model; inflammatory bone loss | Enhanced bone volume | [112] |
| CM | SHED | Atelocollagen sponge | Deficient mice (BALB/c-nu) | Calvarial bone defect model | Enhanced bone regeneration and angiogenesis | [113] |
| CM | BMSCs cultured under cyclic stretch stimulation | Col sponge | Mice | Calvarial defect model | Bone regeneration and angiogenesis were enhanced by CM obtained from the cyclic stretch culture group | [114] |
| CM | GMSC and PDLSC | Col membrane | Wistar rats | Periodontal defect model | Newly formed bone and reduced inflammation | [115] |
| EXO | Adipose-derived stem cells | Polydopamine-coating PLGA | BALB/C mice | Calvarial critical-sized defect | Promoted MSC migration and homing into the new bone | [116] |
| EXO | MSCs | Col/III sponges | Sprague Dawley rats | Periodontal defect model | Regenerated bone and periodontal tissues | [117] |
| EXO overexpressing miR-375 | Adipose-derived stem cells overexpressing miR-375 |
Hydrogel consisting of thiol-modified hyaluronan, HA and thiol-modified heparin | Sprague Dawley rats | Calvarial defects | Enhanced bone regeneration | [118] |
| EXO | BMSCs | Atelocollagen sponges | Wistar rats | Calvarial critical-sized defect | Bones regenerated and angiogenesis occurred | [119] |
| EXO | DPSCs | Tri-block PLGA–PEG–PLGA micro-spheres incorporated into a nanofibrous PLLA scaffold | C57BL/6 mice | Calvarial Defect | Bone tissue regenerated | [120] |
| Small EVs | BMSCs | Gelatin blended with Laponite | Sprague Dawley rats | Periodontitis rat model | Alveolar bone loss, inflammatory infiltration, and collagen destruction diminished | [121] |
| EVs | BMSCs were genetically modified to constitutively express BMP-2 | Collagen tape | Rats | Calvarial bone defect | Increased bone regenerative potential | [122] |
| EXO | BMSC in osteoinductive condition | Mesoporous bioactive glass | Rats | Critical-sized calvarial defect | New bones formed and regenerated | [123] |
| EVs | BMP 2 expressing MSCs | Alginate hydrogel linked with the RGD domain of fibronectin | Rats | Calvarial bone defect model | Enhanced bone regeneration | [124] |
| EVs, or PEI-engineered EVs | GMSCs | PLA | Wistar rats | Calvarial defect | The scaffold containing PEI-EVs, with or without cells, were able to improve bone healing | [125] |
| CM | GMSCs | PLA scaffold | Wistar rats | Calvarial defect | Good osteogenic capacity was observed | [126] |
| CM, EVs, or EVs engineered with PEI | PDLSCs | Col membrane | Wistar rats | Calvarial defect | Increased bone regeneration in association with vascularization | [127] |
| CM | PDLSCs | Evolution membrane | Wistar rats | Calvarial defect | Good osteogenic ability was observed | [128] |
| EVs | GMSCs | PLA | Wistar rats | Calvarial defect | Bone regeneration and vascularization were observed | [129] |
BMP: bone morphogenetic protein; BMSCs: bone marrow-derived MSCs; CM: conditioned medium; Col: collagen; DPSCs: dental pulp stem cells; EVs: extracellular vesicles; EXO: exosomes; GMSCs: gingival-derived MSCs; HA: hydroxyapatite; HCCS: HA Col calcium silicate; MSCs: mesenchymal stem cells; PDLSCs: periodontal ligament stem cells; PEI: polyethylenimine; PLA: polylactic acid; PLGA: polylactic polyglycolic acid; SHED: stem cells from human exfoliated deciduous teeth; TCP: tri-calcium phosphates.