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novel degradable injectable HLC-HPA hydrogel with antiinflammatory activity for biomedical materials: Preparation, characterization, in vivo and in vitro evaluation GAO Shang 1

1,2,3†

, QU LinLin

1,2,3†

, ZHU ChenHui

1,2,3

4

1,2,3*

, OUYANG PingKai & FAN DaiDi

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an 710069, China; 2 Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi’an 710069, China; Biotech & Biomed Research Institute, Northwest University, Xi’an 710069, China; College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China 3

4

Received January 15, 2020; accepted February 25, 2020; published online May 26, 2020

In situ injectable hydrogels, which have great potential in tissue engineering, are characterized by simple preparation, minimal invasiveness and adaptation to complex shapes. However, injectable hydrogels have higher requirements for biocompatibility and safety due to their use in vivo implantation. Therefore, in this study, a human-like collagen (HLC)-based in situ gel-forming injectable HLC-HPA hydrogel was synthesized by combining the amino group of HLC with the carboxyl group of HPA activated using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), followed by crosslinking by horseradish peroxidase (HRP) and H2O2, and used as scaffold material for tissue engineering. The hydrogel stiffness, gel time and biodegradation rate could be easily and independently adjusted by varying the H2O2 and HRP concentrations. Scanning electron microscope (SEM) clarified the homogeneous porous and interconnected internal structures of the hydrogel. In vitro cell viability and in vivo degradation experiments confirmed that the HLC-HPA hydrogel had good biodegradability and excellent biocompatibility. Interestingly, in cultured macrophages, the HLC-HPA hydrogel showed anti-inflammatory activity by reducing the amount of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin6 (IL-6) and increasing the secretion of the anti-inflammatory cytokine interleukin-10 (IL-10) induced by lipopolysaccharide (LPS). Meanwhile, in animal experiments, HLC-HPA hydrogels exhibit excellent biocompatibility and have properties of hemostasis and reduction of inflammatory response. Therefore, the HLC-HPA hydrogel prepared in this study has great potential for development for use in the biomedical field. injectable hydrogels, human-like collagen, biocompatibility, anti-inflammation, hemostasis Citation:

Gao S, Qu L L, Zhu C H, et al. A novel degradable injectable HLC-HPA hydrogel with anti-inflammatory activity for biomedical materials: Preparation, characterization, in vivo and in vitro evaluation. Sci China Tech Sci, 2020, 63, https://doi.org/10.1007/s11431-020-1544-3

1 Introduction Hydrogels, as 3D network biomaterials with hydrophilic polymer chains, can absorb and retain