Dual functional modification of gellan gum hydrogel by introduction of methyl methacrylate and RGD contained polypeptide
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 CCH2 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.