Preparation Of A Self-Healing Bombyx Mori Sericin Hydrogel And Its Cartilage Repair Function

As a common chronic disease,articular cartilage defect severely reduces the quality of life of patients,and the long-term therapeutic effect of traditional treatments perform poorly for such damage.Regenerative medicine technology based on tissue engineering scaffolds and stem cell therapy can effectively facilitate cartilage regeneration,and provide a new therapeutic approach for cartilage repair.Hydrogels are becoming a promising class of biomaterials due to their polymer networks,which mimic physical structure of the extracellular matrix(ECM)to maintain stem cells proliferation and differentiation phenotype.However,high water content leads to poor mechanical properties and short service lifetime of hydrogels,extremely limiting their clinical applications.Therefore,the design and preparation of biocompatible hydrogels capable of self-healing have attracted more and more attentions from material researchers.Bombyx mori silk sericin(SS)exhibits excellent biocompatibility and biodegradability,thus,it is widely utilized in the field of biomaterials.In addition,oxidized sodium alginate(OS A)can be coupled with a variety of biologically active substances,and improve the interaction between materials and cells.Hydroxyapatite(HAp)with excellent osteoinductivity is the main inorganic component of human bones and teeth.However,the brittleness and lack of bending resistance of HAp limit its application as biomaterials.It is often necessary to combine it with other biomaterials to improve its properties.In this study,AD@SSO and AD@SSOH composite self-healing hydrogels were prepared successfully from SS,OS A and HAp by exploiting the dynamic Schiff Base reaction at room temperature.The morphology,structure and mechanical properties of hydrogel scaffolds were characterized by SEM,FTIR,rotational rheometer and universal tensile testing machine respectively.Then the degradation performance,porosity and self-healing property of hydrogels were examined.The effects of hydrogels on the proliferation and differentiation of human bone marrow mesenchymal stem cells(hMSCs)and in vivo cartilage repair were further investigated.The structural and performance characterization results were as follows:both AD@SSO and AD@SSOH composite self-healing hydrogels were porous structure with porosity of over 70%.The hydrogels showed a typical concentration-dependent and pH-response in vitro degradation experiment.Higher concentration hydrogels degraded slower at pH 6.0.The results of rheological recovery,macroscopic observation and strain compression testing indicated that the hydrogels had excellent self-healing ability under physiological conditions without any external stimulation,and self-healing efficiency of AD@SSOH hydrogel was up to 86%.The results of rheological test and mechanical characterization showed that the mechanical properties of the AD@SSOH hydrogel were significantly improved and the maximum stress was 1.73 times higher after HAp was added.The results of cell and animal experiments were as follows:the hydrogels with satisfactory biocompatibility promoted the adhesion,proliferation and chondrogenic differentiation of hMSCs in vitro.The results revealed that the expression levels of chondrocyte specific genes(SOX 9 and COL Ⅱ)of hydrogel groups were markedly upregulated compared with the control group(p<0.05),which further promoted the deposition of more proteoglycan,demonstrating that the AD@SSO and AD@SSOH hydrogels had good effects on promoting the chondrogenic differentiation.Furthermore,in vitro SD rat cartilage defect model experiments proved that compared with the blank control group and AD@SSO hydrogel group,AD@SSOH hydrogel loaded with hMSCs yield the best cartilage repair effects,new cartilage tissue integrated better with surroundings,and cartilage surface was smooth and flat.The above results indicated that the AD@SSO and AD@SSOH self-healing hydrogels prepared in this study not only exhibited good self-healing properties as well as biocompatibility,but also effectively promoted hMSCs chondrogenic differentiation in vitro/in vivo.Therefore,it is a great potential biomaterial in the regeneration of cartilage and other biomedical applications.