Table 3.

Preclinical study on the application of bioscaffolds loaded with cytokines in the repair of articular cartilage injury

Intervening measure	Joint site/implant site of cartilage injury models	Treatment outcomes	Animal model	References
A functional biomaterial using a biphasic scaffold platform and a BMSCs-specific affinity peptide	Trochlear groove of the femur	Functional biomaterials induced better cartilage repair without complications compared to conventional surgery or control scaffolds	Rabbits	Huang et al., [110]
MSCs E7 affinity peptide modified demineralized bone matrix (DBM) particles and CS hydrogel binding composite scaffold	Subcutaneous	This composite scaffold has the ability to promote translucency and superior chondroid structure formation in promoting chondrogenesis	Nude mice	Meng et al., [111]
Composite scaffold were formulated from a combination of HA fibers and PCL fibers, either with TGF-β3	Femoral trochlear groove	This composite scaffold improved histological scores and increased type 2 collagen content	Minipigs	Kim et al., [106]
Mechano growth factor (MGF) and TGF-β3 functionalized silk scaffold	Femoral trochlear groove	Fibroin scaffold loaded with TGF-β3 and MGF could enhance the recruitment of endogenous stem cells and promote the regeneration of articular cartilage in situ	Rabbits	Luo et al., [108]
Water-based polyurethane 3D-printed scaffold with controlled release function	Femoral trochlear groove	The scaffold promotes the self-aggregation of MSCs and induce the differentiation of MSCs into cartilage through timely release of bioactive components to generate substrates for cartilage repair	Rabbits	Hung et al., [123]
Functional scaffold named APM-E7 by conjugating a MSCs affinity peptide (E7) onto the acellular peritoneum matrix (APM)	Femoral trochlear groove	Functional scaffolds loaded with APM-E7 can provide space for MSCs and improve cell homing, two key factors required for cartilage tissue engineering	Rabbits	Meng et al., [112]
TGF-β1-releasing scaffold	Medial condyle of femur	The sustained release of TGF-β1 by this scaffold during osteochondral repair enhances early cartilage differentiation	Minipigs	Asen et al., [95]
Biomimetic cartilage scaffolds with orientated porous structure of two factors (kartogenin and TGF-β1)	Femoral trochlear groove	Biomimetic cartilage scaffolds can effectively repair cartilage defects, which is related to the scaffolds’ ability to guide the morphology, orientation, proliferation and differentiation of BMSCs	Rabbits	Wang et al., [97]
Sustained release SDF-1α/TGF-β1-loaded SF-porous gelatin scaffold	Femoral trochlear groove	This scaffold can promote homing, migration and chondrogenic differentiation of MSCs in vitro. In addition, SDF-1α and TGF-β1 have a synergistic effect in promoting chondrogenesis in vivo	Rats	Chen et al., [98]
Ginsenoside Rb1/TGF-β1 loaded biodegradable SF-gelatin porous scaffold	Femoral trochlear groove	The composite scaffold loaded with Rb1 and TGF-β1 can synergically create a microenvironment conducive to cartilage regeneration by promoting chondrogenesis and inhibiting inflammation levels in the body	Rats	Wu et al., [99]
Biofunctionalized chondrogenic shape-memory ternary scaffold	Femoral trochlear groove	Kartogenin has endowed this scaffold with biological activity that can better promote cartilage repair	Rats	Xuan et al., [114]
Nanofibrous HA scaffold delivering TGF-β3 and SDF-1α	Femoral trochlear groove	This scaffold loaded with SDF-1α and TGF-β3 can effectively promote cartilage formation	Minipigs	Martin et al., [109]
Biomimetic scaffold to deliver kartogenin for long-term cartilage regeneration	Femoral trochlear groove	HA composite lyotropic liquid crystal materials with joint protection and controlled drug release can be used as robust scaffolds to provide long-term cartilage repair	Rats	Wang et al., [116]
Solubilized articular cartilage ECM-derived scaffolds	The medial femoral condyle	This TGF-β3-loaded biological scaffold promoted advanced articular cartilage regeneration	Goats	Browe et al., [107]
A biomimetic scaffold using gelatin methacrylate (GELMA) and polyethylene glycol diacrylate (PEGDA) to wrap KGN	Femoral trochlear groove	The GELMA/PEDGA biomimetic scaffold modified by kartogenin repaired the cartilage defect and restored the cartilage to hyaline cartilage	Rabbits	Yu et al., [115]
Cell-free SF biomaterial scaffolds with bioactive molecules	Femoral trochlear groove	This SF-based biomimetic cartilage biofunctional scaffold with continuous controlled release of E7 and TGF-β1 may significantly promote cartilage regeneration in situ	Rabbits	Mao et al., [96]
A biomaterial scaffold with PRP containing SDF-1	Femoral trochlear groove	The PRF scaffold loaded with SDF-1 can better promote cartilage healing	Rabbits	Bahmanpour et al., [120]
Tricalcium phosphate scaffolds loaded with PRP	Distal articular surface of femur	The tricalcium phosphate scaffold loaded with PRP can well promote cartilage injury repair	Beagles	Li et al., [124]
Platelet-rich concentrates on a HA scaffold	Femoral trochlear groove	The combination of platelet concentrates rich in white blood cells with HA scaffold improves cartilage healing through various pathways	Bovine	Titan et al., [122]
Platelet lysate-rich plasma macroporous hydrogel (PLPMH) scaffold	Femoral trochlear groove	The PLPMH scaffold promote cartilage tissue regeneration by increasing the M2 macrophage ratio	Rabbits	Pan et al., [121]

HA: hyaluronic acid; PCL: poly ε-caprolactone; SF: silk fibroin; MSCs: marrow mesenchymal stem cells; BMSCs: bone marrow mesenchymal stem cells; ECM: extracellular matrix; CS: chitosan; SDF-1α: stromal derived factor-1α; PRP: platelet-rich plasma