Zhaozhao Ding
Qiang Lu
Xiaoyi Zhang
Xiaozhong Zhou
Liying Xiao
Guozhong Lu
David L Kaplan
1 Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China;
2 Department of Burns and Plastic Surgery, Engineering Research Center of the Ministry of Education for Wound Repair Technology, The Affiliated Hospital of Jiangnan University, Wuxi 214041, China;
3 National Engineering Laboratory for Modern Silk&Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China;
4 Department of Orthopedics, Affiliated Hospital of Xuzhou Medical University, Lianyungang 222061, China;
5 Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
Funds: We thank the National Key R&D Program of China (2016YFE0204400), National Nature Science Foundation of China (Grant Nos. 81171712 and 81873995). We also thank the Social Development Program of Jiangsu Province (BE2018626, BE2019662) for support of this work.
Received Date: 2019-12-26
Rev Recd Date:2020-01-14
Abstract
Abstract
Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues. The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials. Incorporation of multiple gradients in the hydrogels remains challenges. Here, betasheet rich silk nanofibers (BSNF) were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field. The blocks migrated to the anode along the electric field and gradually stagnated due to the solution-hydrogel transition of the systems, finally achieving gradient distribution of the blocks in the formed hydrogels. The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity, which resulted in highly tunable gradient of mechanical cues. The blocks were also aligned under the electric field, endowing orientation gradient simultaneously. Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-electric field strategy. The building blocks could be introduced to various hydrogels such as Gelatin and NIPAM, indicating the universality. Complex niches with multiple gradient cues could be achieved through the strategy. Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis. Chondrogenic-osteogenic gradient transition was obtained, which stimulated the ectopic osteochondral tissue regeneration in vivo. The versatility and highly controllability of the strategy as well as multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.Keywords: silk,
building blocks,
gradients,
hydrogel,
tissue regeneration
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