Table 1.
Summary factors influencing the release pattern of EVs for EV-loaded hydrogels.
| Hydrogel components | Sources of EVs | Size of EVs | Sustained release time of EVsa | Factors influencing the release pattern of EVs | References |
|---|---|---|---|---|---|
| Type I collagen | Apis mellifera royal jelly | <150 nm | 7 days | 1 mg/ml: the release rate is highest on the day 3 and continues to decrease thereafter; 2 mg/ml: sustained high release rate over seven days; 3 mg/ml: sustained low release rate over seven days. |
[31] |
| GelMA + LAP | BMSC | 30–250 nm (mean = 130 ± 51 nm) | 14 days | 7% GelMA+0.1% LAP: shows an early burst release; 7% GelMA+0.2% LAP: more prolonged over the first 3 days. In both cases, the release was essentially complete by 14 days. |
[97] |
| HA-tyramine (HA-Tyr) | human cardiomyocyte | 50 nm | 5 days | 3% HA-Tyr: retained almost half of EVs in the first 2 days, while the cumulative release was found until nearly 5 days. | [86] |
| Self-assembling peptides (SAPs) | BMSC | 120.1 ± 55.4 nm | 168 h | The release rate of EVs was dose-dependently accelerated in the presence of MMP2 compared to the blank group. | [23] |
| Atom transfer radical polymerization (ATRP) | nonactivated macrophages J774A.1 |
30–150 nm | up to one month | The monomer-to-crosslinker ratio (molar ratio) and the crosslinking density of the polymer networks both affect the release of EVs. | [124] |
| Ureido-pyrimidinone (UPy) supramolecular (PEG coupled to two UPy units) |
CPCs |
100 nm | up to 2.5 weeks | The molecular weight of the PEG block within it may result in different kinetics of release. With a PEG block of 10 kg mol−1 (UPy10 k) showed a steadier release than UPy20 k. | [109] |
| 8-arm PEG Tren-SG (8P-TS) | M2 macrophages | 32.67–122.4 nm | 5–26 days | The release time of EVs can be regulated from 5 to 26 days by controlling the crosslinking density and tightness of hydrogel. | [77] |
| porcine-derived decellularized ECM | CPCs | / | 7 days | Different tissue sources of ECM can affect the release patterns of EVs. | [126] |
| PF-127 | ADSC | 30–100 nm | 96 h | PF-127 concentration affects the release of EVs. | [167] |
| 4-arm-PEG-MAL | ADSC | / | 20 days | The degradation rate of hydrogels can be controlled to regulate the release of EVs. | [168] |
| Chitosan-Collagen | BMSC | 131.3 ± 11.4 nm | 7 days | The release of EVs from these hydrogel formulations was dependent on chitosan/collagen ratios. | [160] |
Abbreviations: BMSC: Bone marrow mesenchymal stem cells; MSC: mesenchymal stem cells; CPCs: cardiac progenitor cells. PF-127: Pluronic F-127; ADSC: Adipose derived mesenchymal stem cells; PEG: Polyethylene glycol; HA: Hyaluronic acid; MSC: mesenchymal stem cells; GelMA: Gelatin methacryloyl; ECM: extracellular matrix; 4-arm-PEG-MAL: four-armed polyethylene glycol (PEG) functionalized with maleimide group.
a
Notes: The EVs release time here is for reference only and is actually influenced by various factors.