Abstract

Injectable hydrogels have attracted growing interests as promising biomaterials for clinical applications, due to their minimum invasive implanting approach and easy-handling performance. Nevertheless, natural biomaterials-based injectable hydrogels with desirable nontoxicity are suffering from limited functions, failing to fulfill the requirements of clinical biomaterials. The development of novel injectable biomaterials with a combination of biocompatibility and adequate functional properties is a growing urgency toward biomedical applications. In this contribution, we report a simple and effective approach to fabricate multi-functional CMC-OSA-DTP hydrogels. Two kinds of natural polysaccharide derived polymers, carboxymethyl chitosan (CMC) and oxidized alginate (OSA) along with 3,3′-dithiopropionic acid dihydrazide (DTP) were utilized to introduce three dynamic covalent bonds. Owing to the existence of triple dynamic bonds, this unique CMC-OSA-DTP hydrogel possessed smart redox and pH stimuli-responsive property, injectability as well as self-healing ability. In addition, the CCK-8 and live/dead assays demonstrated satisfying cytocompatibility of the CMC-OSA-DTP hydrogel in vitro. Based on its attractive properties, this easy-fabricated and multi-functional hydrogel demonstrated the great potential as an injectable biomaterial in a variety of biomedical applications.

Highlights

  • Hydrogels bear a resemblance to extra cellular matrix (ECM) and enable cells to adhere, proliferate and differentiate, resulting from the three-dimensional crosslinked hydrophilic networks, porous framework and high water content [1,2]

  • “smart” hydrogels, which can respond to various stimuli, such as light [11], heat [12], pH [13], and redox environment [14], have been intensively explored because of their great potential in biomedical applications, including tissue engineering, biosensors, drug delivery systems, and artificial muscle [15,16]

  • To solve the water-insolubility problem of chitosan, various water-soluble chitosan derivatives were successfully developed toward medical applications [17,25]

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Summary

Introduction

Hydrogels bear a resemblance to extra cellular matrix (ECM) and enable cells to adhere, proliferate and differentiate, resulting from the three-dimensional crosslinked hydrophilic networks, porous framework and high water content [1,2]. To solve the water-insolubility problem of chitosan, various water-soluble chitosan derivatives were successfully developed toward medical applications [17,25] Attributed to their desirable intrinsic properties, such as nontoxic, biocompatibility, low immune rejection, and excellent renewability, natural polysaccharide-based injectable hydrogels have showed promising potentials in biomedical fields. Due to the gentle properties of safe ingredients, the resulting hydrogel exhibited remarkable nontoxicity and cytocompatibility as demonstrated by CCK-8 and live/dead assays using MG-63 cells We envision this smart injectable hydrogel based on triple dynamic bonds could offer an opportunity to develop ideal candidates as injectable implanting biomaterials and broaden the application environments in biomedical fields. Schiff base linkages are able to form under mild with a highofreaction rate, which are ideal to prepare biologically relevant hydrogels

Design and Construction
Dual Stimili-Responsiveness of CMC-OSA-DTP Hydrogels
Mechanical Properties and Morphology Observations of Hydrogels
Mechanical
Materials
Synthesis of Oxidation Sodium Alginate
Dual Stimuli-Responsive Tests of Hydrogels
Mechanical Tests of Hydrogels
Dynamic Rheological Measurements of Hydrogels
Cytocompatibility Evaluation of Hydrogels In Vitro
Conclusions
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