Applying Chlorogenic Acid In An Alginate Scaffold Of Chondrocytes Can Improve The Repair Of Damaged Articular Cartilage

Objectives:The repair of articular cartilage damage has been a plagued medical problem because of the poor regenerative ability of cartilage.Alternatively,tissue engineering represents an emerging strategy to substitute and replace the present treatments.Nevertheless,the viability of chondrocytes/stem cells was decreased dramatically after being transplanted into the hypoxic and inflammatory articular cavity.These weak strengths render the further application of cartilage tissue engineering.Therefore,different methods have been used to promote the proliferation of stem cells/chondrocytes.Our current experiment is going to investigate the effects of the tissue engineering cartilage containing chlorogenic acid(CGA),an extract from Eucommia ulmoids Oliv,together with alginate and chondrocytes on the recovery of injuried cartilage,and to explore the underlying biological mechanisms.Methods: Primary cultured chondrocytes were employed to confirm the effects of CGA on chondrogenesis.Then we used an articular cartilage injury model of chick knees and gait analysis following operation,to assess the functional recovery after transplantation of the complexes containing chondrocytes and CGA in an alginate scaffold.Histological analysis and PCR,western blot was further used to illuminate the underlying mechanisms.Results: Firstly,it was proved that CGA in alginate could stimulate chondrogenesis in vitro.Secondly,it was shown that the application of these complexes accelerated the recovery of injury-induced dysfunction by gait analysis.Histochemical analysis then demonstrated that there was less vasculature proliferation and more chondrocyte proliferation and cartilage matrix synthesis in the presence of the complexes containing CGA.Next,we discovered that CGA activated the expressions of Sox9 and Col 2a1 which may be responsible for the stimulation of chondrogenesis.Furthermore,the application of these complexes containing CGA could suppress the increase of inflammatory cytokines IL-1? and TNF-? as well as p-p65,which is achieved through adjusting cellular redox homeostasis associated with Nrf2.Conclusions: Our study suggested that combining chondrocytes and CGA on an alginate scaffold could improve the recovery of damaged articular cartilage,by suppressing the abnormal angiogenesis,fibrosis and inflammation at the injury site.This may be acquired through adjusting cellular redox homeostasis.