Injectable Hyaluronic Acid Hydrogel Scaffold With Kartogenin-encapsulated Nanoparticles For Porcine Cartilage Regeneration

Objective 1.To evaluate the efficacy of hyaluronic acid hydrogel with kartogenin-encapsulated PLGA nanoparticles(m-HA+KGN treatment)on repairing chondral and osteochondral defects in a porcine model.2.To determine the effect of defect size and type(full-thickness chondral vs.osteochondral)on the therapeutic efficacy of m-HA+KGN treatment.Methods Forty-eight minipigs were randomized into three treatment groups,including m-HA hydrogel with KGN-loaded PLGA nanoparticles(m-HA+KGN treatment),m-HA hydrogel(m-HA treatment)and untreated(blank treatment).Full-thickness(FT)chondral(?6.5 mm or 8.5 mm)or osteochondral(?6.5 mm or 8.5 mm,5 mm depth)defects were prepared in the medial femoral condyle.At 6 and 12 months postoperatively,defect repair was assessed by macroscopic appearance,MRI,micro-computed tomography(?CT),histology and biomechanical tests.Results The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively.Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by ?CT were observed in the m-HA+KGN group.The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix,cartilage lacuna and type II collagen.The biomechanical properties were improved in the m-HA+KGN group.With m-HA+KGN treatment,defects with a size of ?6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared to ?8.5 mm or osteochondral-type defects.Conclusion 1.m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up.2.m-HA+KGN treatment demonstrated higher therapeutic efficacy in defects with size of ?6.5 mm or full-thickness chondral-type defects.