TY - JOUR
T1 - Fabrication of injectable, porous hyaluronic acid hydrogel based on an in-situ bubble-forming hydrogel entrapment process
AU - Wang, Lixuan
AU - Dong, Shiyan
AU - Liu, Yutong
AU - Ma, Yifan
AU - Zhang, Jingjing
AU - Yang, Zhaogang
AU - Jiang, Wen
AU - Yuan, Yuan
N1 - Funding Information:
This research was funded by the National Natural Science Foundation of China for Innovative Research Groups (number 51621002), the National Natural Science Foundation of China (number 31771040), and Leading talents in Shanghai in 2017The authors wish to express their gratitude to the financial support from the National Natural Science Foundation of China for Innovative Research Groups (number 51621002), the National Natural Science Foundation of China (number 31771040), the National Key R&D Program of China (2018YFC1105700), and Leading talents in Shanghai in 2017.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - In-situ bubble-forming hydrogel entrapment
KW - Injectable hydrogel
KW - Porous structure
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U2 - 10.3390/POLYM12051138
DO - 10.3390/POLYM12051138
M3 - Article
C2 - 32429363
AN - SCOPUS:85086503079
SN - 2073-4360
VL - 12
JO - Polymers
JF - Polymers
IS - 5
M1 - 1138
ER -