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A Carbodiimide Cross-Linked Silk Fibroin/Sodium Alginate Composite Hydrogel with Tunable Properties for Sustained Drug Delivery
Authors:Yiyu Wang  Chunqing Niu  Jian Shi  Wenlong Yu  Chunhong Zhu  Qin Zhang  Mamoru Mizuno
Affiliation:1. Institute of Nanobiomaterials and Immunology, School of Life Science, Taizhou University, Taizhou, 318000 P. R. China

Hubei Province Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Hubei Engineering University, Xiaogan, 432000 P. R. China;2. Hubei Province Research Center of Engineering Technology for Utilization of Botanical Functional Ingredients, Hubei Engineering University, Xiaogan, 432000 P. R. China;3. Department of Mechanical Engineering, Faculty of Systems Science and Technology, Akita Prefectural University, Akita, 015-0055 Japan;4. Faculty of Textile Science and Technology, Shinshu University, 3-15-1 Tokida, Ueda, Nagano, 386-8567 Japan;5. Institute of Translational Medicine, Shanghai University, Shanghai, 200444 China

Abstract:Carbodiimide cross-linked silk fibroin (SF)/sodium alginate (SA) composite hydrogels with superior stability and tunable properties are developed by varying preparation parameters. SF/SA blend ratio modulation allows to achieve composite hydrogel gelation times of 18–65 min, and rheological analysis shows that the speed of gel formation, the hydrogel network's density, and the hydrogels’ compressive properties are closely related to the blend ratio. The G′ of different hydrogels varies substantially from 28 to 413 Pa, and the hydrogel with higher SF content has a greater stiffness. The composite hydrogels present appropriate porosity of 76.63–85.09% and pore size of 316–603 µm. Hydrogel stability improves significantly after cross-linking, and substantial swelling occurs due to the hydrophilicity of SA. The 7/3 and 6/4 SF/SA hydrogels are more resistant to degradation in PBS, and cytotoxicity testing confirmed their biocompatibility. For release studies in vitro, two model compounds are used as drug models, tetracycline hydrochloride, and bovine serum albumin (BSA). Different ratios of SF/SA have a greater influence on the release of BSA. This study provides a practical preparation method for flexible SF/SA composite hydrogels, which can help design hydrogels with specific physicochemical properties for different applications, especially drug delivery.
Keywords:composite hydrogels  silk fibroin  sodium alginate
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