Fabrication of protease XIV-loaded microspheres for cell spreading in silk fibroin hydrogels

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DELIVERY SYSTEMS Original Research

Fabrication of protease XIV-loaded microspheres for cell spreading in silk fibroin hydrogels Wenqian Xiao1,2 Jing Zhang1,2 Xiaohang Qu1,2 Ke Chen1,2 Haiming Gao1,2 Jisu He1,2 Tao Ma1,2 Bo Li1 Xiaoling Liao2 ●















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Received: 16 January 2020 / Revised: 12 May 2020 / Accepted: 3 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Due to their excellent mechanical strength and biocompatibility, silk fibroin(SF) hydrogels can serve as ideal scaffolds. However, their slow rate of natural degradation limits the space available for cell proliferation, which hinders their application. In this study, litchi-like calcium carbonate@hydroxyapatite (CaCO3@HA) porous microspheres loaded with proteases from Streptomyces griseus (XIV) were used as drug carriers to regulate the biodegradation rate of SF hydrogels. The results showed that litchi-like CaCO3@HA microspheres with different phase compositions could be prepared by changing the hydrothermal reaction time. The CaCO3@HA microspheres controlled the release of Ca ions, which was beneficial for the osteogenic differentiation of mesenchymal stem cells (MSCs). The adsorption and release of protease XIV from the CaCO3@HA microcarriers indicated that the loading and release amount can be controlled with the initial drug concentration. The weight loss test and SEM observation showed that the degradation of the fibroin hydrogel could be controlled by altering the amount of protease XIV-loaded CaCO3@HA microspheres. A three-dimensional (3D) cell encapsulation experiment proved that incorporation of the SF hydrogel with protease XIV-loaded microspheres promoted cell dispersal and spreading, suggesting that the controlled release of protease XIV can regulate hydrogel degradation. SF hydrogels incorporated with protease XIV-loaded microspheres are suitable for cell growth and proliferation and are expected to serve as excellent bone tissue engineering scaffolds. Graphical Abstract

These authors contributed equally: Wenqian Xiao, Jing Zhang Supplementary information The online version of this article (https:// doi.org/10.1007/s10856-020-06466-7) contains supplementary material, which is available to authorized users. * Bo Li [email protected] * Xiaoling Liao [email protected] 1

Chongqing Key Laboratory of Nano/Micro Composite Materials

and Devices, Chongqing University of Science and Technology, Chongqing 401331, China 2

Chongqing Engineering Laboratory of Nano/Micro Biomedical Detection Technology, Chongqing University of Science and Technology, Chongqing 401331, China

128 Page 2 of 12

Journal of Materials Science: Materials in Medicine (2020)31:128

Keywords Silk fibroin Hydrogel protease XIV CaCO3@HA microspheres ●





1 Introduction Due to their special physical properties, which mimic those of the native extracellular matrix (ECM), hydrogels are widely used as tissue engineering scaffolds [1, 2]. In particular, hydrogels provide a unique means of cell enc