Table 1.
The therapeutic applications of natural and synthetic biopolymer-based scaffolds that utilize extracellular vesicles. The type of EV and biopolymer used in each study are indicated as well as the EV incorporation method into the scaffold.
| Study | EV Source | Scaffold Biomaterial | Modifications and/or EV Incorporation Method | Disease or Tissue | Animal Models | Therapeutic Outcomes |
|---|---|---|---|---|---|---|
| [33] | Human adipose-derived mesenchymal stem cell (hADMSC) EVs | Silk-based tubular scaffold | Vacuum-seeded EVs | Cardiovascular disease | Rat abdominal aortic interposition graft model | Improved patency and matrix deposition, including increased elastin and collagen production |
| [26] | Bone marrow-derived mesenchymal stem cell (BMSC) sEVs | Sodium Alginate | sEVs mixed with sodium alginate solution | Myocardial infarction (MI) | MI induction in male rats | Decreased cardiac cell apoptosis Promotion of macrophage polarization Increased scar thickness and angiogenesis Improved cardiac function and infarct size |
| [37] | Human umbilical cord mesenchymal stem cell (HUCMSCs) Exosomes | Polyvinyl alcohol (PVA)/Alginate | Exosomes mixed with PVA/alginate solution | Diabetic wound healing | Full-thickness wounds on diabetic rat model | Proliferation, migration, and angiogenesis of HUVECs Sped up diabetic wound healing by promoting angiogenesis |
| [38] | ADSC-derived Exosomes | Sodium Alginate | Exosomes mixed with alginate solution | Peripheral nerve regeneration | Rat sciatic nerve defect | Exosomes containing neurotrophin-3 mRNA (important neurotrophic factor for peripheral nerve regeneration) in scaffold promoted nerve regeneration |
| [39] | Dental pulp stem cell (DPSC)-derived EVs | Collagen | EVs were injected into the scaffold | Bone regeneration | Rat calvarial bone defect | Bone formation in center of defects Broader angiogenesis |
| [40] | HUCMSCs | Collagen | Exosomes added dropwise onto scaffold | Endometrium regeneration and fertility restoration | Rat endometrium-damage model | Induction of endometrium regeneration, collagen remodeling Increased expression of estrogen receptor α/progesterone receptor Restored fertility Facilitated CD163+ M2 macrophage polarization, reduced inflammation, increased anti-inflammatory responses |
| [32] | BMSC EVs | Chitosan-Collagen Composite Scaffold | Scaffolds seeded with EVs | Skin wound healing | Full-thickness skin wound on adult male rats | Accelerated skin healing Enhanced macrophage count Greater collagen deposition, better collagen alignment and thus, increased mechanical strength |
| [41] | Bone mesenchymal stem cell-derived sEVs | Chitosan | sEVs added to hydrogels | Bone defect repair | Calvarial defect rat model | sEV-loaded hydrogel promoted bone healing by enhancing angiogenesis possibly via upregulation of miR-21 in sEVs |
| [42] | Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) exosomes | Chitosan | Exosomes stirred into chitosan solution | Corneal diseases | Rat cornea anterior lamellar damage model | Promote repair of damaged corneal epithelium and stromal layer |
| [43] | Chondrocyte exosomes | Chitosan-Gelatin-Chondroitin Sulfate and Nano-Hydroxyapatite-Gelatin | Exosome suspension added dropwise over scaffold | Articular cartilage injuries | N/A | Enhance proliferation and migration of chondrocytes |
| [44] | Osteoblast-derived EVs | Gelatin Methacryloyl (GelMA) | GelMA functionalized with nanoclay laponite | Bone regeneration | N/A | Enhanced proliferation, migration, histone acetylation, mineralization of human bone marrow stromal cells |
| [45] | Tendon derived stem cells (TDSCs) exosomes | Hyaluronic acid | Loaded scaffold–not sufficiently described | Tendon repair | Rat model of tendon defects | Promoted proliferation, migration, collagen type I production, and tendon-specific markers expression in tenocytes Protected tenocytes from oxidative stress and serum deprivation Promoted early healing of injured tendons and better fiber arrangement at injury site |
| [46] | Human articular chondrocyte-derived EVs | Hyaluronic acid/Chitosan | Loaded scaffold–not sufficiently described | Osteoarthritis cartilage injuries | Rabbit osteochondral defect model | Greater cartilage regeneration Provide niche for chondrogenic differentiation of MSCs Hyalin-like cartilage in defect zone |
| [47] | M2 polarized macrophage-derived Exosomes (M2-Exos) | PEG | Dissolved freeze-dried PEG in exosome solution | Cutaneous wound healing | Mouse excisional wound splinting model | Localization and sustained release of M2-Exos Effective and prolonged conversion of M1 to M2 macrophages Enhanced efficiency and quality of wound care |
| [48] | hADMSC-derived exosomes | PLA | Mineral doped PLA scaffolds adsorbed exosomes | Bone defects including oral bone defects | N/A | Increased osteogenic commitment of MSCs |
| [49] | Mesenchymal stem cell (MSC)-derived sEVs | PCL | sEVs loaded onto heparin-modified scaffold | Cardiovascular disease | Hyperlipidemia rat model | Inhibited thrombosis and calcification and thus improved patency of graft Enhanced endothelium and vascular smooth muscle regeneration Induced polarization of M1 macrophages to M2c macrophages |
| [50] | MSC-exosomes | PCL | PCL modified with S-nitrosoglutathione (GSNO); exosomes incubated with scaffold | Bone defects | N/A | Decreased expression of pro-inflammatory genes in macrophages treated with exosome-loaded scaffold Accelerated osteogenic differentiation of mesenchymal stem cells |
| [51] | MSC-derived EVs | PLGA | EVs infused into composite scaffold; polydeoxyribonucleotide (PDRN) added | Chronic kidney disease | Partial nephrectomy mouse model | Synergistic interaction of EVs and other added compounds in scaffold alleviates fibrosis and inflammatory response Cellular proliferation Angiogenesis Effective glomerular regeneration Restoration of kidney function Develop new blood vessels and induces pro-reparative macrophages |
| [52] | Human adipose-derived stem cell exosomes | PLGA | Scaffolds submerged in exosome solution | Bone defects | Mouse calvarial defect | Enhance bone regeneration partially through osteoinductive effects and promoting mesenchymal stem cell migration and homing in newly formed bone tissue |
| [53] | MSC-sEVs | PEG/Hyaluronic Acid | sEVs mixed with scaffold solution | Osteoarthritis (OA) | Traumatic OA rat model | Improved bioavailability and therapeutic efficacy of MSC-sEVs for OA improvement |
| [54] | Human DPSC-derived exosomes | PLLA | Exosome encapsulation in triblock PLGA-PEG-PLGA microspheres and subsequently incorporated into PLLA scaffold | Bone defects | Critical size mouse calvarial bone defect | Stimulated bone tissue neogenesis Facilitated bone marrow stromal cell osteogenic differentiation Guided local progenitor cells towards osteogenic differentiation and bone healing Accelerated bone healing |