Elsevier

Materials Letters

Volume 264, 1 April 2020, 127341
Materials Letters

Dual functional modification of gellan gum hydrogel by introduction of methyl methacrylate and RGD contained polypeptide

https://doi.org/10.1016/j.matlet.2020.127341Get rights and content

Highlights

  • A gellan gum hydrogel with sequential MA and RGD peptides modification was prepared.

  • The mechanics of gellan gum hydrogel can be controlled by changing MA grafting ratio.

  • The incorporation of RGD peptides improves the bioactivity of gellan gum hydrogel.

Abstract

For tissue fabrication and tissue regeneration, three-dimension (3D) hydrogel matrix with both cellular bioactivity and versatile fabrication ability for in-situ cell laden is always challenging and spotlight. In this study, we establish a facile approach to modify gellan gum (GG) for overcoming its disadvantages, including high gelling temperature which is incompatible for in-situ cell encapsulation and the native inactivity for cell adhesion. By esterification reaction, methacrylic anhydride modified GG (MAGG) is prepared, producing photo-reactivity for crosslinking and grafting with RGD-contained peptides. Therefore, RGD-grafted hydrogel (MAGG-RGD) is feasibly prepared. Detail characterizations show that MAGG hydrogel possesses improved physicochemical properties, with tunable strength varied with MA dose. Moreover, the introduction of RGD domains significantly improves the MG63 cells proliferation, adhesion and spreading both on two-dimension (2D) surface and in 3D matrix. Given the native photo-crosslinkable capacity, tunable physicochemical nature and good bioactivity, MAGG-RGD hydrogel is perspective in tissue fabrication and tissue engineering, and expands the potential material platform for cell carrier or tissue scaffold.

Introduction

For tissue fabrication and tissue regeneration, 3D hydrogel matrix with both cellular bioactivity and versatile fabrication ability for in-situ cell laden is always challenging and spotlight [1], [2]. Regarding the complexity of composite materials, the exploration of new bioactive material with single component is always perspective. As a type of natural polymer polysaccharide, gellan gum (GG) has temperature-responsive gelation property, biocompatibility, and low toxicity, thus gains increasing attention in biomaterial and tissue engineering [3], [4]. The issues of GG hydrogel using as cell scaffold or carrier mainly include the followings: the higher gelation temperature is incompatible for cell encapsulation [5]; the brittle mechanical strength limits its using for tissue fabrication [6]; in particular, lacking of cell adhesion sites suppresses cell adhesion, restricting its application as cell carrier [7].

The backbone chain of GG consists of 4 repeated sugar units, with a large amount of hydroxyl groups. Therefore, GG molecules can be easily modified via chemical reactions to obtain derivatives with various designable properties [8]. Inspired by the photo-crosslinking ability of MA molecules, as well as the well-known bioactivity of RGD-peptides, we herein aim to prepare MAGG firstly by esterification reaction, and then RGD-contained peptides are feasible to bind into MAGG molecule chains via the Michael-addition reaction. Then a dual-functional modified GG hydrogel, namely MAGG-RGD hydrogel, would be obtained by UV crosslinking. With photo-crosslinkable capability and introduced cell adhesion domains, the single component hydrogel should be perspective candidate for biofabrication and significantly enhance the bioactivity by supporting cell adhesion and spreading, as schemed in Fig. 1A.

Section snippets

Experimental section

MAGG was synthesized via reaction of MA with GG at 50 ℃ with pH 8.0 for 6 h. MAGG-RGD was synthesized via reaction of RGD-contained peptides with MAGG at room temperature with pH 8.0 for 2 h. Nuclear magnetic resonance (NMR) was used to characterize the materials. MAGG and MAGG-RGD hydrogels were prepared under UV lights at 8 mW/cm2 for 20 s. Compression modulus and degradation of the hydrogels were characterized. Human osteoblast-like cells (MG63 cells) were cultured within the hydrogels and

Modification of gellan gum-based material

As shown in Fig. 1B, MA modification on GG was proceeded based on the esterification reaction between carbonyl in MA and hydroxy in GG molecular chain, and the RGD-contained peptides can be easily grafted into MAGG molecular chain via Michael-addition reaction [8], [9]. Via adjusting the addition of MA, MAGG with various MA grafting ratio can be obtained easily (Fig. S1 and Fig. 1D). As shown in Fig. 1C, comparing to GG, the absorption peaks which generated from two 1H in typical single bondCdouble bondCH2 exist at

Conclusion

In this study, MA was successfully grafted into GG molecules with varied MA content. More importantly, MA modified GG is photo-reactive thus RGD peptide can be easily introduced. Therefore, photo-crosslinkable GG hydrogel with in-situ cellular encapsulation compatibility was prepared. By adjusting the ratio of MA and GG, the mechanics and degradation properties of these hydrogels can be precisely regulated, which is beneficial for designing customized biomaterial scaffolds with different

CRediT authorship contribution statement

Ji Jiang: Writing - original draft, Methodology Conceptualization. Yajun Tang: Software, Data curation Methodology, Conceptualization. Hua Zhu: Methodology. Dan Wei: Writing - review & editing. Jing Sun: Writing - review & editing. Hongsong Fan: Supervision, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work is supported by National Natural Science Foundation of China (No. 51673128 and No. 51603030) and Sichuan Science and Technology Program 2018JY0172.

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These authors contributed equally to this work.

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