Table 3.
Summary of in vivo studies on exosome-based therapy in craniofacial and dental application
| Tissue | Model/Species | Exosome Origin | Involved Pathway | Administration Methods |
Functional Effects | Ref |
|---|---|---|---|---|---|---|
| Bone regeneration | Calvarial bone defect/ Osteoporotic rats | hiPSC-MSCs | — | β-TCP scaffold | Promote osteogenesis and angiogenesis | 60 |
| Calvarial bone defect/ Mice | hADSCs | — | PLGA scaffold | Promote osteogenesis | 62 | |
| Calvarial bone defect/ Rats | hiPSC-MSCs | PI3K/Akt | β-TCP scaffold | Promote osteogenesis | 81 | |
| Calvarial bone defect/ Rats | miR-375- overexpressed hADSCs | — | Hydrogel | Promote osteogenesis | 61 | |
| Calvarial bone defect/ Rats | DMOG-stimulated hBMSCs | AKT/mTOR | Porous HA scaffold | Stimulate angiogenesis | 67 | |
| Calvarial bone defect/ Mice | hPSCs | SAPK/JNK, HGF, Sirtuin, FGF, PDGF, AMPK, PTEN | Percutaneous injection | Promote osteogenesis | 63 | |
| Alveolar bone defect/ Rats | SHEDs | AMPK | β-TCP scaffold | Promote osteogenesis and angiogenesis | 82 | |
| BRONJ/Rats | hBMMSCs | — | Tail vein injection | Promote angiogenesis and bone regeneration | 83 | |
| TMJ regeneration | TMJ osteoarthritis/Rats | hESC-MSCs | AKT, ERK, AMPK | Intra-articular injection | Suppress inflammation and pain , reduce apoptosis, enhance matrix synthesis | 88 |
| Periodontal regeneration | Periodontitis/Rat | rADSCs | — | Pocket local injection | Anti-inflammatory effect, enhance osteoid tissues and blood vessels formation | 93 |
| Periodontal intrabony defects/Rats | hESC-MSCs | AKT, ERK | Collagen sponge | Enhance osteogenesis and periodontal ligament formation | 94 | |
| Periodontitis/Human clinical trial | hADSCs | — | Local injection into periodontal pockets | — | NCT04270006 | |
| Dental pulp regeneration | Tooth root slice model/Mice | hDPSCs under odontogenic conditions | P38 MAPK | Collagen membrane | Promote stem cell differentiation and blood vessels formation | 105 |
| Skin regeneration | Full-thickness skin wounds/ Diabetic mice | mADSCs | — | FEP hydrogel | Stimulate angiogenesis and enhance cell proliferation, granular tissue formation, collagen deposition, remodeling and re-epithelialization | 106 |
| Full-thickness skin wounds/ Diabetic mice | mADSCs | — | FHE hydrogel | Promote angiogenesis, re- epithelialization and collagen deposition | 107 | |
| Full-thickness skin wounds/ Rat | rADSCs | — | Alginate hydrogel | Enhance re-epithelialization, collagen deposition and angiogenesis | 108 | |
| Full-thickness skin wounds/ Diabetic rats | hGMSCs | — | Chitosan/silk hydrogel sponge | Promote re-epithelialization, deposition and ECM remodeling and enhance angiogenesis and neuronal ingrowth | 109 | |
| Full-thickness skin wounds/ Mice | HucMSCs | TGF-β/SMAD2 | HydroMatrix hydrogel | Suppress myofibroblast aggregation and scar formation | 110 | |
| Full-thickness skin wounds/ Mice | hADSCs | PI3K/Akt | subcutaneous and intradermal injection | Promote collagen synthesis and optimize collagen deposition | 111 | |
| Full-thickness skin wounds/ Mice | hMenSCs | NF- kB | Intradermal injection | Induce M1-M2 macrophage polarization, enhance neoangiogenesis and re-epithelialization | 112 | |
| Full-thickness skin wounds/ Mice | hBMMSCs | — | Intravenous injections | Promote macrophages towards M2 polarization | 113 | |
| Full-thickness skin wounds/ Diabetic mice | miR-21-5p overexpressed hADSCs | Wnt/β-catenin | Direct addition, coverage with alginate gel | Enhance re-epithelization, collagen remodeling, angiogenesis and vessel maturation | 114 | |
| Full-thickness skin wounds/Diabetic mice | mmu_circ_0000250 overexpressed mADSCs | miR-128-3p/SIRT1 | Subcutaneous injection | Promote angiopoiesis and suppress apoptosis by autophagy | 115 | |
| Full-thickness skin wounds/ Diabetic rat | hPRP | RhoA/YAP, PI3K/Akt, Erk1/2 | Sodium alginate hydrogel | Promote angiogenesis | 116 | |
| Skin wound model/ Mice | mM2 Mφs | — | Subcutaneous injection | Enhance angiogenesis, re-epithelialization, and collagen deposition | 117 | |
| Full-thickness skin wounds/ Rats | hOMECs | — | Direct addition, coverage with TegaDerm and gauze | Reduce fibroblast proliferation and stimulate the release of growth factors | 118 | |
| Full-thickness skin wounds/ Mice | hUCB | PTEN, SPRY1 | Subcutaneous injection | Promote re-epithelization and angiogenesis | 119 | |
| Deep second-degree burn wound/ Rats |
HucMSCs | Yap, Wnt/β-Catenin | Subcutaneous injection | Restrict stem cell expansion and collagen deposition | 120 | |
| Deep second-degree burn wound/ Rats |
HucMSCs | Wnt/β-Catenin, AKT | Subcutaneous injection | Enhance proliferation of skin cells and promote re-epithelialization | 121 | |
| UVB-Induced skin photoaging/ Mice | HDFs | TGF-β | Dermo-jet model G (needleless injection) | Regulate dermal fibroblasts to induce efficient collagen biosynthesis and ameliorate inflammation | 122 | |
| Full-thickness gingival wound/ Mice | mGMSCs | Fas/Fap-1/Cav-1 | Submucosally injection | Produce high amounts of IL-1RA | 124 | |
| Oral Cancer | DMBA-induced OSCC/ Hamsters | hMenSCs | — | Injection into the base of the tumor | Reduce tumor vasculature | 131 |
| OPMD | DMBA-induced OPMD/ Hamsters | microRNA-185 overexpressed mBM-MSCs | Akt | Solution painting | Alleviate inflammation, inhibit cell proliferation and angiogenesis and induce apoptosis | 133 |
| Others | Free-falling induced TBI/ Rats | SHEDs | — | Injection into rat brains |
Shift microglia M1/M2 polarization | 135 |
| Critical-sized tongue defect/ Rats | hGMSCs | — | SIS-ECM | Promote reepithelialization, reinnervation and taste bud regeneration | 136 |
hiPSC-MSC: human induced pluripotent stem cells-derived mesenchymal stem cells; β-TCP: β-tricalcium phosphate; hADSCs: human adipose-derived mesenchymal stem cells; PLGA: poly(lactic-co-glycolic acid); DMOG: dimethyloxaloylglycine; hBMSCs: human bone mesenchymal stem cells; HA: hydroxyapatite; hPSCs: human perivascular stem cells; SHEDs: stem cells from human exfoliated deciduous teeth; TMJ: temporomandibular joint; hESC-MSCs: human embryonic stem cell-derived MSCs; rADSCs: rat adipose-derived stem/stromal cells; hDPSCs: human dental pulp stem cells; mADSCs: mice adipose-derived mesenchymal stem cells; FEP: F127 (F127) grafting polyethylenimine (PEI) and aldehyde pullulan (APu); FHE: multifunctional hydrogel composed of Pluronic F127, oxidative hyaluronic acid and Poly-ε-L-lysine; hGMSCs: human gingival mesenchymal stem cells; ECM: extracellular matrix; HucMSCs: human umbilical cord mesenchymal stem cells; hMenSCs: human menstrual blood-derived mesenchymal stem cells; hBMMSCs: human bone marrow-derived mesenchymal stem cells; hPRP: human platelet-rich plasma; mM2 Mφs: mice M2 phenotype macrophages; hOMECs: human oral mucosa epithelial cells; hUCB: human umbilical cord blood; HDFs: human dermal fibroblasts; mGMSCs: mice gingiva-derived mesenchymal stem cells; DMBA: dimethylbenzanthracene; OPMD: oral potentially malignant disorders; mBM-MSCs: mice bone marrow-derived mesenchymal stem cells; TBI: traumatic brain injury; BRONJ: bisphosphonate-related osteonecrosis of the jaw; SIS-ECM: small intestinal submucosa-extracellular matrix.