Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process
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 injecta...
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MDPI AG
2020-05-01
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author | Lixuan Wang Shiyan Dong Yutong Liu Yifan Ma Jingjing Zhang Zhaogang Yang Wen Jiang Yuan Yuan |
author_facet | Lixuan Wang Shiyan Dong Yutong Liu Yifan Ma Jingjing Zhang Zhaogang Yang Wen Jiang Yuan Yuan |
author_sort | Lixuan Wang |
collection | DOAJ |
description | 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, CO<sub>2</sub> 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. |
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spelling | doaj.art-3725500a9b5c4b3d8c8fda88118cae9a2023-11-20T00:40:46ZengMDPI AGPolymers2073-43602020-05-01125113810.3390/polym12051138Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment ProcessLixuan Wang0Shiyan Dong1Yutong Liu2Yifan Ma3Jingjing Zhang4Zhaogang Yang5Wen Jiang6Yuan Yuan7Key Laboratory for Ultrafine Materials of Ministry of Education, and School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, ChinaDepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USAKey Laboratory for Ultrafine Materials of Ministry of Education, and School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, ChinaDepartment of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USADepartment of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USADepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USAKey Laboratory for Ultrafine Materials of Ministry of Education, and School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, ChinaInjectable 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, CO<sub>2</sub> 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.https://www.mdpi.com/2073-4360/12/5/1138injectable hydrogelporous structurein-situ bubble-forming hydrogel entrapment |
spellingShingle | Lixuan Wang Shiyan Dong Yutong Liu Yifan Ma Jingjing Zhang Zhaogang Yang Wen Jiang Yuan Yuan Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process Polymers injectable hydrogel porous structure in-situ bubble-forming hydrogel entrapment |
title | Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process |
title_full | Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process |
title_fullStr | Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process |
title_full_unstemmed | Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process |
title_short | Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process |
title_sort | fabrication of injectable porous hyaluronic acid hydrogel based on an in situ bubble forming hydrogel entrapment process |
topic | injectable hydrogel porous structure in-situ bubble-forming hydrogel entrapment |
url | https://www.mdpi.com/2073-4360/12/5/1138 |
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