Non-Cochrane · intervention · PM42050594
Therapeutic efficacy of mesenchymal stem cell-derived extracellular vesicles combined with injectable hydrogels in bone defect repair: a systematic review and meta-analysis of preclinical studies.
Aghayan Amir Hossein, Mohammadi Davood, Samarkhazan Hamed Soleimani, et al. · Journal of biological engineering · 2026 · PubMed · doi:10.1186/s13036-026-00684-3
Findings
109 findings
| Population | ||||
|---|---|---|---|---|
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 3.52 [1.79, 5.26] GRADE not reported 9 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Kuang 2023 | SMD 3.82 [1.85, 5.79] GRADE not reported 8 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models | SMD 6.47 [4.74, 8.19] GRADE not reported 10 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Lei Qi [2025] | SMD 6.52 [4.26, 8.79] GRADE not reported 15 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Jiajia Deng [2023] | SMD 5.84 [3.85, 7.82] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Li Wang [2024] | SMD 6.52 [4.26, 8.78] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Li 2022 | SMD 4.03 [1.17, 6.89] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Tissue source of MSCs: Bone marrow | SMD 6.75 [4.07, 9.43] GRADE not reported 10 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Shuo Yang 2020 | SMD 5.12 [0.67, 9.57] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shenghui Su [2024] | SMD 5.86 [3.95, 7.77] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Yuntong Zhang [2021] | SMD 6.17 [4.1, 8.25] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sample size per group (ARRIVE): 6 or more animals per group | SMD 7.08 [4.12, 10.03] GRADE not reported 10 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Wei Lu [2023] (RUNX2) | SMD 6.59 [4.68, 8.49] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Zhang 2021 | SMD 7.09 [1.41, 12.78] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shuang Han [2023] | SMD 6.56 [4.31, 8.82] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Overall risk of bias: Low risk | SMD 3.94 [1.39, 6.48] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Li 2022 | SMD 7.69 [2.52, 12.87] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Meta-regression: EV dosage | Meta-regression coefficient (SMD per unit EV dose) 0.0108 GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular number (Tb.N) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Wan 2025 | SMD 7.37 [5.09, 9.65] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 3.53 [1.20, 5.87] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Overall risk of bias: Unclear risk | SMD 2.98 [0.52, 5.43] GRADE not reported 4 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Liangyan Sun [2024] | SMD 6.15 [4.05, 8.25] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Defect location: Skull | SMD 7.41 [3.68, 11.15] GRADE not reported 9 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Tissue source of MSCs: Dental pulp | SMD 4.66 [2.63, 6.68] GRADE not reported 2 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shuo Yang [2020] | SMD 4.51 [3.3, 5.72] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Li Wang [2024] | SMD 4.99 [3.45, 6.53] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Keyu Luo [2024] (OPN) | SMD 6.3 [4.51, 8.09] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Modification status of MSCEVs: Modified (engineered) | SMD 4.84 [2.42, 7.27] GRADE not reported 4 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Lei Qi [2025] (OCN) | SMD 6.4 [4.56, 8.25] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | RUNX2 expression Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 5.86 [4.22, 7.50] GRADE not reported 3 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Keyu Luo [2024] | SMD 6.11 [4.0, 8.23] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 6.30 [4.26, 8.33] GRADE not reported 16 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Rongkang Guo [2023] (OPN) | SMD 6.77 [4.94, 8.6] GRADE not reported 13 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shaowei Pan [2023] | SMD 5.64 [3.63, 7.66] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Rongkang Guo [2023] | SMD 6.59 [4.33, 8.84] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Zhang 2021 | SMD 3.56 [0.77, 6.35] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Yang 2023 | SMD 3.26 [1.41, 5.11] GRADE not reported 8 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Lei Qi [2025] (OPN) | SMD 6.21 [4.48, 7.94] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Species origin of MSCs: Animal | SMD 4.70 [2.59, 6.81] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular number (Tb.N) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 7.52 [5.47, 9.58] GRADE not reported 4 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Jiajia Deng [2023] | SMD 6.45 [4.19, 8.72] GRADE not reported 15 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shenghui Su [2024] | SMD 6.54 [4.27, 8.8] GRADE not reported 15 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Yang Yang [2023] (OCN) | SMD 6.18 [4.44, 7.92] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Modification status of MSCEVs: Unmodified | SMD 2.27 [0.42, 4.11] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Jiabing Fan [2020] | SMD 5.78 [3.91, 7.65] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Qi 2025 | SMD 3.26 [1.44, 5.08] GRADE not reported 8 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longlong He [2023] (RUNX2) | SMD 6.66 [4.78, 8.55] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Species origin of MSCs: Animal | SMD 6.39 [3.44, 9.34] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Hydrogel type: Synthetic polymer | SMD 4.47 [2.45, 6.50] GRADE not reported 2 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Li 2022 | SMD 3.98 [2.22, 5.73] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular number (Tb.N) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Zhang 2021 | SMD 8.25 [5.95, 10.55] GRADE not reported 3 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longbiao Wan [2025] | SMD 5.33 [3.51, 7.15] GRADE not reported 11 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Hydrogel type: Natural polymer | SMD 2.93 [0.81, 5.05] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Lu 2023 | SMD 7.68 [2.46, 12.89] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Yuntong Zhang [2021] (OCN) | SMD 6.78 [5.0, 8.57] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Hydrogel type: Natural-synthetic hybrid | SMD 9.40 [-0.46, 19.26] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sample size per group (ARRIVE): Fewer than 6 animals per group | SMD 4.05 [0.45, 7.64] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Ming 2024 | SMD 3.78 [1.78, 5.79] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Hydrogel type: Natural polymer | SMD 6.27 [3.72, 8.82] GRADE not reported 10 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 6.46 [1.85, 11.06] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Species origin of MSCs: Human | SMD 0.98 [0.07, 1.90] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sample size per group (ARRIVE): 6 or more animals per group | SMD 3.40 [1.22, 5.59] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sample size per group (ARRIVE): Fewer than 6 animals per group | SMD 4.57 [2.27, 6.88] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Qi 2025 | SMD 4.88 [0.96, 8.80] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Defect location: Mandible | SMD 3.81 [0.29, 7.32] GRADE not reported 2 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Rongkang Guo [2023] | SMD 5.82 [3.82, 7.82] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longlong He [2023] (OCN) | SMD 6.23 [4.48, 7.98] GRADE not reported 13 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Yang Yang [2023] | SMD 5.42 [3.81, 7.03] GRADE not reported 15 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shuo Yang [2020] (OCN) | SMD 6.09 [4.42, 7.77] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Hydrogel type: Natural-synthetic hybrid | SMD 4.70 [1.75, 7.64] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Modification status of MSCEVs: Modified (engineered) | SMD 6.60 [3.63, 9.56] GRADE not reported 9 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Haizhu Kuang [2023] | SMD 6.68 [4.55, 8.8] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Pan 2023 | SMD 3.09 [1.42, 4.77] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Defect location: Mandible | SMD 4.51 [2.91, 6.12] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular number (Tb.N) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Luo 2024 | SMD 7.19 [4.86, 9.52] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Meta-regression: EV dosage Unresolved: the two extractors disagree on this row. | Meta-regression coefficient (SMD per unit EV dose) -0.0076 GRADE not reported Studies not reported |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Species origin of MSCs: Human | SMD 6.92 [3.00, 10.84] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Osteopontin (OPN) expression Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 7.22 [2.79, 11.65] GRADE not reported 3 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Lu 2023 | SMD 4.20 [1.62, 6.78] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Liangyan Sun [2024] | SMD 5.28 [3.53, 7.03] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Keyu Luo [2024] | SMD 5.47 [3.54, 7.4] GRADE not reported 11 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular thickness (Tb.Th) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Pan 2023 | SMD 6.53 [0.76, 12.30] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Rui Li [2022] | SMD 6.68 [4.64, 8.72] GRADE not reported 15 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longlong He [2023] | SMD 5.72 [3.69, 7.75] GRADE not reported 11 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longlong He [2023] | SMD 6.62 [4.38, 8.86] GRADE not reported 15 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Zhang 2021 | SMD 3.60 [1.65, 5.55] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Wan 2025 | SMD 3.10 [1.45, 4.74] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Overall risk of bias: Low risk | SMD 5.95 [3.45, 8.45] GRADE not reported 9 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Modification status of MSCEVs: Unmodified | SMD 6.20 [2.93, 9.47] GRADE not reported 6 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Li Wang [2024] (BMP2) | SMD 6.83 [5.11, 8.55] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Fan 2020 | SMD 3.16 [0.55, 5.77] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Shuo Yang 2020 | SMD 2.33 [0.88, 3.78] GRADE not reported 5 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Shuo Yang [2020] | SMD 5.78 [3.88, 7.68] GRADE not reported 15 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Leiguo Ming [2024] | SMD 5.83 [4.07, 7.59] GRADE not reported 11 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Defect location: Long bones | SMD 5.48 [3.07, 7.90] GRADE not reported 3 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longbiao Wan [2025] (RUNX2) | SMD 6.18 [4.49, 7.88] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Overall risk of bias: Unclear risk | SMD 7.01 [3.25, 10.77] GRADE not reported 6 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Angiogenesis (CD31 expression) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Ming 2024 | SMD 3.95 [1.05, 6.85] GRADE not reported 5 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Defect location: Skull | SMD 2.93 [0.85, 5.01] GRADE not reported 6 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Yuntong Zhang [2021] (BMP2) | SMD 6.76 [4.96, 8.57] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 8 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Tissue source of MSCs: Umbilical cord | SMD 11.42 [7.18, 15.65] GRADE not reported 2 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Yuntong Zhang [2021] | SMD 5.56 [3.66, 7.47] GRADE not reported 11 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Lu 2023 | SMD 3.91 [1.99, 5.83] GRADE not reported 8 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | BMP2 expression Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 2.57 [0.99, 4.16] GRADE not reported 2 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Osteocalcin (OCN) expression Preclinical animal bone defect models (skull, mandible/alveolar, long bone) | SMD 7.66 [4.96, 10.36] GRADE not reported 6 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Osteogenic markers overall (OCN, OPN, BMP2, RUNX2) Not specified (end of follow-up) · Preclinical animal bone defect models · Leave-one-out sensitivity: omitting Longbiao Wan [2025] (OCN) | SMD 6.56 [4.68, 8.43] GRADE not reported 13 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Trabecular number (Tb.N) Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Sensitivity analysis: leave-one-out omitting Shuo Yang 2020 | SMD 7.22 [4.61, 9.83] GRADE not reported 3 studies |
| Mammals (mostly rats, some mice) with surgically induced bone defects | MSC-derived extracellular vesicles loaded in injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold without MSCEVs | Bone mineral density (BMD) Not specified (end of follow-up) · Preclinical animal bone defect models | SMD 5.45 [3.74, 7.17] GRADE not reported 12 studies |
| Mammalian animal models with surgically induced bone defects | MSC-derived extracellular vesicles delivered via injectable hydrogels (MSCEV-IH) | Untreated defect or empty scaffold/hydrogel without MSCEVs | Bone volume fraction (BV/TV) 4 weeks · Preclinical animal bone defect models (skull, mandible/alveolar, long bone) · Tissue source of MSCs: Bone marrow | SMD 4.70 [2.59, 6.81] GRADE not reported 6 studies |
Included primary studies 19
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Haizhu Kuang 2023 Integrated Osteoinductive Factors─Exosome@MicroRNA-26a Hydrogel Enhances Bone Regeneration DOI:10.1021/acsami.2c21933 | 2023 | this review only | not stated | not extracted yet |
| Jiabing Fan 2020 Generation of Small RNA-Modulated Exosome Mimetics for Bone Regeneration DOI:10.1021/acsnano.0c05122 | 2020 | this review only | not stated | not extracted yet |
| Jiajia Deng 2023 Versatile Hypoxic Extracellular Vesicles Laden in an Injectable and Bioactive Hydrogel for Accelerated Bone Regeneration DOI:10.1002/adfm.202211664 | 2023 | this review only | not stated | not extracted yet |
| Keyu Luo 2024 Harnessing bone marrow mesenchymal stem cell-derived extracellular vesicles and biomimetic peptide WKYMVm in self-healing hydrogel for… DOI:10.1177/20417314241306681 | 2024 | this review only | not stated | not extracted yet |
| Lei Qi 2025 Engineered extracellular vesicles with sequential cell recruitment and osteogenic functions to effectively promote senescent bone repair DOI:10.1186/s12951-025-03168-6 | 2025 | this review only | not stated | not extracted yet |
| Leiguo Ming 2024 Small Extracellular Vesicles Laden Oxygen-Releasing Thermosensitive Hydrogel for Enhanced Antibacterial Therapy against Anaerobe-Induced… DOI:10.1021/acsbiomaterials.3c00493 | 2024 | this review only | not stated | not extracted yet |
| Li Wang 2024 Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration DOI:10.1021/acsnano.3c11542 | 2024 | this review only | not stated | not extracted yet |
| Liangyan Sun 2024 Enhanced Tissue Regeneration Through Immunomodulatory Extracellular Vesicles Encapsulated in Diversified Silk‐Based Injectable Hydrogels DOI:10.1002/adhm.202401460 | 2024 | this review only | not stated | not extracted yet |
| Longbiao Wan 2025 PI3K/Akt pathway-mediated enhancement of bone and vascular regeneration by gelatin/hyaluronic acid/exosome composite scaffold in bone… DOI:10.1016/j.bioadv.2024.214064 | 2025 | this review only | not stated | not extracted yet |
| Longlong He 2023 PF127 Hydrogel-Based Delivery of Exosomal CTNNB1 from Mesenchymal Stem Cells Induces Osteogenic Differentiation during the Repair of… PMID:36985977 | 2023 | this review only | not stated | not extracted yet |
| Rongkang Guo 2023 Biomimetic composite hydrogel promotes new bone formation in rat bone defects through regulation of miR-19b-3p/WWP1 axis by loaded… DOI:10.1186/s12951-023-02201-w | 2023 | this review only | not stated | not extracted yet |
| Rui Li 2022 Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF DOI:10.1186/s13287-022-02823-1 | 2022 | this review only | not stated | not extracted yet |
| Shaowei Pan 2023 Multifunctional Injectable Hydrogel Microparticles Loaded with miR‐29a Abundant BMSCs Derived Exosomes Enhanced Bone Regeneration by… DOI:10.1002/smll.202306721 | 2023 | this review only | not stated | not extracted yet |
| Shenghui Su 2024 Enhanced repair of osteoporotic bone defects through gelatin methylacryloyl loaded with exosomes DOI:10.1063/5.0220157 | 2024 | this review only | not stated | not extracted yet |
| Shuang Han 2023 Programmed release of vascular endothelial growth factor and exosome from injectable chitosan nanofibrous microsphere-based PLGA-PEG-PLGA… DOI:10.1016/j.ijbiomac.2023.126721 | 2023 | this review only | not stated | not extracted yet |
| Shuo Yang 2020 Integration of Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes with Hydroxyapatite-Embedded Hyaluronic Acid-Alginate Hydrogel… DOI:10.1021/acsbiomaterials.9b01363 | 2020 | this review only | not stated | not extracted yet |
| Wei Lu 2023 Human urine-derived stem cell exosomes delivered via injectable GelMA templated hydrogel accelerate bone regeneration DOI:10.1016/j.mtbio.2023.100569 | 2023 | this review only | not stated | not extracted yet |
| Yang Yang 2023 Injectable MMP1-sensitive microspheres with spatiotemporally controlled exosome release promote neovascularized bone healing DOI:10.1016/j.actbio.2022.11.065 | 2023 | this review only | not stated | not extracted yet |
| Yuntong Zhang 2021 Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis DOI:10.1021/acsami.0c22671 | 2021 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Mammalian animal models with surgically induced bone defects at any anatomical site, any sex, strain or age | 19 preclinical studies: rats (n=17) and mice (n=2); skull (11), long bone (3), mandible/alveolar (4) defects |
| Intervention | MSC-derived extracellular vesicles delivered via injectable hydrogels | MSCEVs (bone marrow, umbilical cord, adipose, dental pulp, urine sources) in natural, synthetic or hybrid injectable hydrogels (n=19) |
| Comparison | Untreated defect groups or empty scaffolds without therapeutic agents | Untreated defect or empty/non-loaded scaffold controls (n=19) |
| Outcomes | Primary: BV/TV. Secondary: BMD, Tb.N, Tb.Th, angiogenesis (CD31), osteogenic markers (OCN, OPN, BMP2, RUNX2) | BV/TV at 4 weeks (9 studies) and 8 weeks (16 studies); BMD (12 forest rows); Tb.N (4); Tb.Th (6); CD31 angiogenesis (6); OCN, OPN, BMP2, RUNX2 |
| Study designs | Original controlled animal studies, randomized or non-randomized | Controlled preclinical animal studies (n=19) |
| Timing | Not specified | 4 weeks and 8 weeks for BV/TV |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | No | No | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: Partial Yes · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: Yes · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | Yes | Yes | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |