Preparation Of Succinic Anhydride-modified Icariin And Its Application In Bone And Cartilage Tissue Engineering

Working as regeneration promoter,most of the growth factors are relatively expensive,unstable and highly immunogenic.Thus,replacement of the conventional growth factors with the new stable and easy-to-acquire bioactive molecule is important.Icariin(Ica),a stable flavonoid,was found to promote the reparation of bone and cartilage.In this study,Ica was used as a promoter and separately added to the bone and cartilage tissue engineering scaffolds.Ica was firstly modified to prepare Succinic acid modified Icariin(Ica-SA),then the carboxyl group of Ica-SA was covalently bonded to the amino group of CHS via esterification,to synthesize Ica-CHS.Next,hydroxyapatites(HAp)and hyaluronic acid(HA)were separatelyintroduced to prepare the Ica-CHS/HAp and Ica-CHS/HA composite scaffold,to construct the long-term effective bone and cartilage tissue engineering scaffold.Main results were shown below.(1)Succinic acid modified Icariin(Ica-SA)was synthesized by esterification of succinic anhydride(SA)and Ica,and the carboxyl groupwas introduced into Ica-SA,and the substitution degree was identified as ~2.5.(2)Ica-SA was covalently linked to CHS via amidation reaction to prepare Ica-CHS and the drugloading efficiency and release profile were tested.Results indicated that the drug-loadingefficiency was about 3.6%,and drug on the Ica-CHS mainly release through the hydrolysis of amido and ester bonds.Furthermore,used as amide condensation agent,1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDCI)and N-hydroxysuccinimide(NHS)were used to react with CHS,results showed that an anti-acid chitosan-based hydrogelwas formed.(3)Osteoinductive HAp nanoparticles were incorporated to prepare the Ica-CHS/HAp composite scaffold.Ica was observed sustainly released and stimulated the proliferation and osteogenic differentiation of BMSCs.(4)The Ica-CHS/HA composite scaffolds were fabricated by composing Ica-CHS and hyaluronic acid(HA).Data also showed that,Ica could be constantly released from the scaffold in a stable manner and maintained the chondrocytes’ phenotype.Results showedthat Ica-CHS/HApand Ica-CHS/HA composite scaffolds mightbe the promising candidate in bone tissue engineering and cartilage tissue engineering.