PMID- 28812170 OWN - NLM STAT- MEDLINE DCOM- 20180618 LR - 20220410 IS - 1573-9686 (Electronic) IS - 0090-6964 (Linking) VI - 45 IP - 11 DP - 2017 Nov TI - A Novel Approach to Utilize Icariin as Icariin-Derived ECM on Small Intestinal Submucosa Scaffold for Bone Repair. PG - 2673-2682 LID - 10.1007/s10439-017-1900-y [doi] AB - 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. FAU - Li, Mei AU - Li M AD - Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, 315211, Zhejiang, People's Republic of China. AD - Ningbo Institute of Medical Sciences, Ningbo, 315020, Zhejiang, People's Republic of China. FAU - Zhang, Chi AU - Zhang C AD - Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, 315211, Zhejiang, People's Republic of China. FAU - Zhong, Yi AU - Zhong Y AD - Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, 315211, Zhejiang, People's Republic of China. FAU - Zhao, Jiyuan AU - Zhao J AUID- ORCID: 0000-0002-1327-7119 AD - Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, 818 Fenghua Road, Ningbo, 315211, Zhejiang, People's Republic of China. zhaojiyuan@nbu.edu.cn. LA - eng PT - Journal Article DEP - 20170815 PL - United States TA - Ann Biomed Eng JT - Annals of biomedical engineering JID - 0361512 RN - 0 (Flavonoids) RN - VNM47R2QSQ (icariin) SB - IM MH - Animals MH - *Bone Regeneration MH - Cell Adhesion/drug effects MH - Cell Line MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - *Extracellular Matrix MH - Flavonoids/*pharmacology MH - *Intestinal Mucosa MH - *Intestine, Small MH - Male MH - Mice, Inbred C57BL MH - Osteoblasts/drug effects/physiology MH - Tissue Engineering MH - *Tissue Scaffolds OTO - NOTNLM OT - Biocompatibility OT - Bone tissue engineering OT - Extracellular matrix (ECM) OT - Osteoblast OT - Osteoconductivity OT - Osteoinductivity EDAT- 2017/08/16 06:00 MHDA- 2018/06/19 06:00 CRDT- 2017/08/17 06:00 PHST- 2017/05/26 00:00 [received] PHST- 2017/08/09 00:00 [accepted] PHST- 2017/08/16 06:00 [pubmed] PHST- 2018/06/19 06:00 [medline] PHST- 2017/08/17 06:00 [entrez] AID - 10.1007/s10439-017-1900-y [pii] AID - 10.1007/s10439-017-1900-y [doi] PST - ppublish SO - Ann Biomed Eng. 2017 Nov;45(11):2673-2682. doi: 10.1007/s10439-017-1900-y. Epub 2017 Aug 15.