Table 2.
Tissue-specific applications of EV-loaded hydrogels.
| Tissue/organ to be regenerated | Hydrogel | Sources of EVs | Application strategies | Key findings | Reference |
|---|---|---|---|---|---|
| Skin/Wound healing | PF-127 | ADSC | Topical administration | PF-127 hydrogel-loaded EVs can effectively promote wound healing. | [167] |
| MMP-PEG smart hydrogel | ADSC | Topical administration | It can target the MMP2 response and significantly promote the recovery of diabetic wounds. | [168] | |
| HAMA Microneedle | MSC-EVM | Microneedle (MN) | MN patches containing EVs show the ability to deliver deep into the skin. | [62] | |
| Chitosan/Silk hydrogel sponge | gingival MSC | Wound Dressing | Demonstrated the feasibility of hydrogel sponge dressings loaded with EVs for use on wound. | [176] | |
| HA@MnO2/FGF-2 hydrogel | M2 macrophages | Topical administration | Simultaneous loading of nanoenzymes and bioactive factors as well as EVs provides a multifunctional effect, improving all aspects of wound healing. | [193] | |
| Chitosan/Silk hydrogel sponge | platelet-rich plasma | Wound Dressing | Combined application of active ingredients in Chinese medicine with EVs shows great potential. | [192] | |
| MC-CHO and CS-g-PEG | MSC | Topical administration | Self-healing hydrogels can synergize with EVs to promote wound healing. | [191] | |
| Bone and cartilage | HyStem-HP hydrogel (Catalog: GS315, Glycosan Biosystems) | UCSC | Topical administration | EV-loaded hydrogel can promote repair from fractures. | [194] |
| GelMA/Laponite | BMSC | in vitro only | Nanoclay combined with hydrogel can induce stem cell bone differentiation, showing great promise in bone repair. | [162] | |
| PEG/MC/β-TCP | BMSC | Topical administration | The composite hydrogel improves the local microenvironment and exhibits better mechanical strength. | [202] | |
| PLGA-PEG-PLGA microsphere/PLLA scaffold | dental pulp stem cells DPSC | Scaffold | Polymeric microspheres loaded with EVs combined with scaffolds can be used for the repair of skull defects. | [115] | |
| HA/nHP scaffolds | UMSC | Scaffold | EV-loaded hydrogel to encapsulate the nanoceramic scaffold can be used to repair large bone defects. | [199] | |
| CGC/HG | chondrocytes | Scaffold | Double-layered composite scaffold structure loaded with EVs holds promise for articular cartilage repair. | [207] | |
| AD/CS/RSF | BMSC | Topical administration | Mussel-like high adhesion hydrogel loaded EVs allows better adhesion to cartilage tissue for better repair. | [103] | |
| Heart | Gelatin and Laponite | ADSC | Topical administration | Intramyocardial injection of EV-loaded hydrogel can contribute to the recovery of the infarcted area. | [214] |
| HA Conductive Hydrogel | UMSC | Topical administration | EV- loaded conductive hydrogels can be adapted to the bioelectricity of the heart and are more promising | [216] | |
| ECM hydrogel | iPS-CPCs | Injection into the pericardial cavity | Intrapericardial injection of EV-loaded hydrogel is minimally invasive and effective. | [217] | |
| GelMA | MSC | Spray drug administration | The authors propose an injection-free delivery of EV-loaded hydrogel to the heart. | [27] | |
| Nerves | GelMA | BMSC | Topical administration | EV-loaded injectable hydrogel for minimally invasive treatment of spinal cord injury. |
[220] |
| HA/GelMA | MSC | Topical administration | Low-stiffness EV-loaded hydrogels showed better repair of injured peripheral nerves. | [221] | |
| Electroconductive hydrogels | BMSC | Topical administration | EV-loaded electroconductive hydrogels match the electrical and mechanical properties of neural tissue and promote tissue repair after spinal cord Injury. |
[26] | |
| GelMA Microneedle | MSC (3D culture) | Microneedle | The authors proposed a controlled 3D-EV-loaded hydrogel microneedle array patch to achieve spinal cord injury repair in situ. | [224] | |
| Reproductive System | Ag-PEG | ADSC | Topical administration | EV-loaded hydrogel improves the intrauterine environment and promotes fertility recovery. | [227] |
| PDNPs-PELA thermosensitive hydrogels | ADSC | Topical administration | EV-loaded hydrogel promotes the repair of penile corpus cavernosum tissue and the recovery of erectile function. | [230] | |
| Periodontal | Gelatin/Laponite | BMSC | Topical administration | EV-loaded hydrogel promotes periodontal tissue repair and regeneration. | [232] |
| Hair | OSA hydrogels | Dermal papilla cell | Topical administration | EV-loaded hydrogel accelerates the regrowth of hair and can be used to treat alopecia. | [139] |
| CL microneedle | ADSC | Microneedle | Such transdermally administrated microneedle patches provide a simple, safe and efficient strategy for hair regeneration. | [238] | |
| Liver | PEG | MSC | Intraperitoneal injection | EV-loaded hydrogel based on click reaction has potential for systemic drug delivery. | [148] |
Abbreviations: PF-127: Pluronic F-127; ADSC: Adipose derived mesenchymal stem cells; MMP: matrix metalloproteinase; PEG: Polyethylene glycol; HAMA: Hyaluronic acid Methacryloyl; BMSC: Bone marrow mesenchymal stem cells; MSC: mesenchymal stem cells; HA: Hyaluronic Acid; MC-CHO: Aldehyde methylcellulose; CS-g-PEG: chitosan-g-PEG; GelMA: Gelatin methacryloyl; LAP: Lithium Phenyl (2,4,6-trimethylbenzoyl) phosphinate; β-TCP: β-Tricalcium Phosphate; PLGA: poly (lactic-co-glycolic acid; PLLA: poly(l-lactic acid); nHP: nanohydroxyapatite/poly-ε-caprolactone; CGC: chitosan-gelatin-chondroitin sulfate; HG: nano-hydroxyapatite-gelatin; AD/CS/RSF: alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin; UMSC: umbilical cord mesenchymal stem cells; ECM: extracellular matrix; iPS-CPCs: pluripotent stem cell-derived cardiac progenitors; PDNPs-PELA: Polydopamine nanoparticles incorporated poly (ethylene glycol)-poly(ε-cap-rolactone-co-lactide); OSA: oxidized sodium alginate; CL: chitosan lactate.