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] |
| Â | 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] |
| Â | 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 | Â | 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] |
| Â | 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] |