Table 1.

Recent preclinical studies on ADSC-based optimization strategies for bone regeneration

ADSC-based optimization strategies		Models	Methods	Results	References
Bioscaffolds	Heterogeneous deproteinized bone (HDB)	Rat radial defect model	ADSCs seeded onto the HDB were implanted into the defective area	ADSC-HDB composites exhibited a strong osteogenic ability	Liu et al. [89]
	Modified hierarchical mesoporous bioactive glass (MBG) scaffold	Rat femoral defect model	Osteogenically induced ADSCs were seeded on the MBG scaffolds prevascularized by endothelial-induced ADSCs; the composite scaffolds were implanted into the defective area	Time-phased sequential application of ADSCs on the MBG scaffolds promoted better angiogenesis and mineral deposition	Du et al. [90]
Genetic modification + Bioscaffolds	Transduction of BMP-2; Biofabricated cryogel scaffolds	Mouse atrophic non-union model	ADSCs were seeded onto biofabricated cryogel scaffolds after BMP-2 transduction and implanted into the non-union site	ADSC-seeded cryogels promoted osseous healing	Hixon et al. [94]
	miR-150-5p inhibition; Hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic powder	BALB/c nu/nu mice	miR-150-5p-modified ADSCs were loaded in HA/TCP ceramic powders and implanted into the dorsal surface of BALB/c nu/nu mice	Combination of ADSCs, miR-150-5p inhibition, and HA/TCP promoted bone damage repair and bone regeneration	Wang et al. [95]
Engineered ADSC spheroids		Mouse calvarial defect model	ADSCs were assembled with PDGF and biomineral-coated fibers to form spheroids and implanted into the defective area	ADSC spheroids incorporating PDGF and biominerals exhibited greater endothelial lineage mRNA expression and vascularized bone regeneration	Lee et al. [91]
		Mouse calvarial defect model	ADSCs were assembled with adenosine and polydopamine-coated fibers to form spheroids and implanted into the defective area	ADSC spheroids impregnated with engineered fibers enabled adenosine delivery and promoted bone regeneration with enhanced osteogenic differentiation	Ahmad et al. [92]
ADSC-Exos + Bioscaffolds	Gelatin nanoparticles (GNPs)	Rat skull defect model	ADSC-Exos loaded within GNPs were implanted into the defective area	GNP-ADSC-Exos effectively regulated bone immune metabolism and promoted bone healing partly via the immune regulation of miR-451a	Li et al. [17]
	Metal–organic framework (MOF) scaffolds	Rat calvarial defect model	ADSC-Exos were coated on the PLGA/Mg-GA MOF scaffold and implanted into the defective area	PLGA/Exo-Mg-GA MOF scaffolds promoted osteogenesis and satisfactory osseointegration	Kang et al. [57]
	PLGA/pDA scaffolds	Mouse calvarial defect model	ADSC-Exos were immobilized on PLGA/pDA scaffolds and then implanted into the defective area	Composite of ADSC-Exos and PLGA/pDA scaffolds enhanced bone regeneration, partially via their osteoinductive effects and by promoting stem cell migration and homing	Li et al. [96]
	Gelatin sponge/polydopamine (GS-PDA) scaffolds	Rat femoral defect model	ADSC-Exos-modified GS-PDA scaffolds (GS-PDA-Exos) were implanted into the defective area	GS-PDA-Exos promoted osteogenesis and bone repair	Li et al. [99]
ADSC-Exos + Genetic modification + Bioscaffolds	Exosomes derived from genetically modified ADSCs; Hydrogel comprising thiol‐modified hyaluronan, hydroxyapatite, and thiol‐modified heparin	Rat calvarial defect model	Exosomes derived from miR-375-overexpressing ADSCs were embedded in hydrogels and implanted into the defective area	ADSC-Exos enriched with miR-375 could enhance bone regeneration	Chen et al. [56]