Table 3.

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

ADSC-based optimization strategies		Models	Methods	Results	References
ADSCs	ADSCs preconditioned with GDF-6 and PDGF-BB; collagen/alginate gel	Rat model of Achilles tendon excision defect	Tenogenically differentiated ADSCs with the hydrogel were injected into the defective area	Tenogenically differentiated ADSCs enhanced the collagen fiber dispersion range closest to the normal tendon	Norelli et al. [147]
	ADSCs induced by GDF-5 and PDGF; collagen/alginate gel	Rat model of Achilles tendon defect	ADSCs pre-treated with hydrogel were injected into the tendon defect area	GDF5/PDGF-induced ADSCs promoted tendon repair by improving cellular proliferation, tenogenesis, and vascular infiltration	Fitzgerald et al. [142]
Engineered ADSCs	ADSC sheets	Rat model of chronic rotator cuff tear	ADSC sheets were transplanted into the rotator cuff tear area	ADSC sheets significantly enhanced the biomechanical properties of the repaired rotator cuff	Shin et al. [148]
Engineered ADSCs + Bioscaffolds	ADSC sheets (P(LLA-CL)/Silk fibroin nanoyarn scaffolds	Rabbit model of patellar tendon defect	GDF-5-induced ADSC sheets were seeded on nanoyarn scaffolds and implanted into the patellar tendon defect area	GDF-5-induced ADSC sheets stimulated higher expression of tenogenesis-related markers and promoted functional tendon regeneration	Chen et al. [28]
Bioscaffolds	Fibrin or gelatin methacrylate [GelMA]	Rat model of massive rotator cuff tears	ADSCs seeded in fibrin or GelMA hydrogel were implanted into the repair site	ADSCs combined with fibrin or GelMA hydrogel could decrease bone loss and augment the efficacy of surgical repair	Rothrauff et al. [150]
	Novel injectable porous gelatin microcryogels (GMs)	Rat model of acute Achilles tendon rupture	GMs loaded with ADSCs were injected into the gap	ADSCs with GMs could effectively improve the macroscopic appearance, histological morphology, and biomechanical properties of the repair tissue	Yang et al. [151]
ADSC-Exos		Rat model of a massive rotator cuff tear	ADSC-Exos were injected into the damaged site	ADSC-Exos treatment could prevent atrophy, fatty infiltration, and inflammation and promote myofiber regeneration and the biomechanical properties of the injured rotator cuff	Wang et al. [155]
		Rabbit model of chronic rotator cuff tear	ADSC-Exos were injected into the repair site	ADSC-Exos could prevent fatty infiltration, improve biomechanical properties, and promote tendon–bone healing after surgical repair	Wang et al. [54]
ADSC-Exos + Bioscaffolds	Hydrogel	Rat model of rotator cuff injury	ADSC-Exos-hydrogel complex was injected in the shoulder after surgical repair	ADSC-Exos-hydrogel promoted rotator cuff repair by mediating the differentiation of the tendon-derived stem cells	Fu et al. [156]
	In situ-forming fibrin gel	Rabbit model of partial-thickness rotator cuff tears	Local administration of in situ-forming fibrin gel containing ADSC-Exos (ADSC-Exos/fibrin)	ADSC-Exos/fibrin significantly prevented tear progression, enhanced the biomechanical properties of the injured tendon, and promoted high-quality tendon healing	Wang et al. [157]