Table 2 Technological advances towards functional modification for ASCs EVs

Engineering EVs^a

Transfecting: mmu_circ_0000250, cirRNA_100395, miR-323-3p, miR-188-3p, miR-301a-3p, miR-29a-3p, miRR-28-3p, circAKap7, GDNF, miR-320d, miR‐375, miR-671, miR-191, miR-181-5p, miR-122, miR-21

Indirectly up-regulating expression of functional molecules into ASCs EVs

[14, 17, 21, 26, 34, 35, 44, 45, 49, 72, 77, 79, 82, 113, 125, 181]

Engineering EVs^b

Transfecting: miR-381-3p, miR-10a, miR-21-5p

Directly up-regulating expression of functional molecules of ASCs EVs

[22, 37, 142]

Hypoxia

Hypoxia pre-condition in different methods

Enhancing pro-metabolism and pro-survival abilities. Angiogenesis, increasing levels of VEGF/VEGFR, attenuating inflammation. ECM repair/regeneration

[20, 67, 85, 86, 102, 103]

Controlled release

Biohybrid bovine bone matrix loaded with EVs

Continuous release of osteogenic factors for bone healing and regeneration

[50]

polypeptide-based FHE hydrogel/oxygen releasing antioxidant and antibacterial cryogel wound dressing OxOBand/hyaluronic acid/polysaccharide-based dressing/alginate hydrogel loaded with EVs

Continuous release of EVs for diabetic/non-diabetic wound healing

[88, 139, 140, 144, 145]

Osteoinduction

ASCs were osteogenically induced using OM

Bone healing and regeneration

[104, 151, 182]

Chondrogenesis

ASCs were osteogenically induced using CM

Cartilage healing and regeneration

[160]

LLLI

A 24-h expose to LLLI before EVs collection

Reducing apoptosis of osteocyte induced by hypoxia

[152]

Inflammatory stimuli

TNF-α pre-condition for 3 days

Enhancing the potential of EVs in bone healing and regeneration

[114]

IFNγ and TNFα

Increasing the immunosuppressive and anti-inflammatory potential of EVs

[92]

Growth factors

20 ng/ml PDGF, VEGF or FGF stimuli

Enhancing angiogenic potential

[19]

Lean adipose

Comparing ASCs EVs from lean and obese adipose

Having differences in size, cargo and bioactivities

[11, 159]