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Open AccessArticle

Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process

by Lixuan Wang 1,2,†, Shiyan Dong 3,†, Yutong Liu 1,2, Yifan Ma 4, Jingjing Zhang 4, Zhaogang Yang 3,*, Wen Jiang 3,* and Yuan Yuan 1,2,*
1
Key Laboratory for Ultrafine Materials of Ministry of Education, and School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China
2
Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China
3
Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
4
Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Polymers 2020, 12(5), 1138; https://doi.org/10.3390/polym12051138
Received: 15 April 2020 / Revised: 13 May 2020 / Accepted: 13 May 2020 / Published: 16 May 2020
(This article belongs to the Special Issue Hydrogels in Tissue Engineering and Regenerative Medicine II)
Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO2 bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics. View Full-Text
Keywords: injectable hydrogel; porous structure; in-situ bubble-forming hydrogel entrapment injectable hydrogel; porous structure; in-situ bubble-forming hydrogel entrapment
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MDPI and ACS Style

Wang, L.; Dong, S.; Liu, Y.; Ma, Y.; Zhang, J.; Yang, Z.; Jiang, W.; Yuan, Y. Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process. Polymers 2020, 12, 1138.

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