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A Novel Approach to Utilize Icariin as Icariin-Derived ECM on Small Intestinal Submucosa Scaffold for Bone Repair

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Abstract

Icariin (Ic) has been demonstrated as a potent osteoinductive compound for bone tissue engineering. However, toxic side effects of the drug and poor biocompatibility of drug delivery systems (DDSs) still limit its application for bone repair in the clinic. To overcome these disadvantages and utilize the osteoinductivity of Ic, we developed a novel method to utilize Ic as an Ic-derived osteoinductive extracellular matrix (ECM) on small intestinal submucosa (SIS) (Ic-ECM-SIS). The generated Ic-ECM-SIS scaffolds, as a natural construct, exhibited much better biocompatibility (including cell adhesion, cell survival and cell proliferation) than Ic-SIS scaffolds generated by traditional DDSs. Meanwhile, osteogenic differentiation was promoted by Ic-ECM-SIS with higher expression of alkaline phosphatase, bone sialoprotein and osteocalcin than ECM-SIS, which was same as Ic-SIS. BMP-4 expression was further increased in the cells on Ic-ECM-SIS compared to that on Ic-SIS. A mouse calvarial defect model was introduced to evaluate the function of Ic-ECM-SIS on bone regeneration in vivo. The bone regeneration was enhanced in the defects implanted with Ic-ECM-SIS, with a higher new bone formation ratio (BV/TV) than the defects implanted with ECM-SIS or Ic-SIS. Angiogenesis was also promoted by Ic-ECM-SIS implantation when compared with ECM-SIS or Ic-SIS. Thus, this work proposes a novel method for applying a drug as a drug-derived ECM-modified scaffold for bone tissue engineering.

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Acknowledgments

We thank Cook Biotech, Inc., for kindly providing lyophilized SIS scaffolds. This work was supported by the Applied Research Project on Nonprofit Technology of Zhejiang Province (No. 2017C33135), the Natural Science Foundation of Ningbo (Grant Nos. 2014A610238 and 2014A610220) and the K.C. Wong Magna Fund in Ningbo University.

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  1. Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, 315211, Zhejiang, People’s Republic of China

    Mei Li, Chi Zhang, Yi Zhong & Jiyuan Zhao

  2. Ningbo Institute of Medical Sciences, Ningbo, 315020, Zhejiang, People’s Republic of China

    Mei Li

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  1. Mei Li
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Associate Editor Michael S. Detamore oversaw the review of this article.

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Li, M., Zhang, C., Zhong, Y. et al. A Novel Approach to Utilize Icariin as Icariin-Derived ECM on Small Intestinal Submucosa Scaffold for Bone Repair. Ann Biomed Eng 45, 2673–2682 (2017). https://doi.org/10.1007/s10439-017-1900-y

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