Synchronous delivery of hydroxyapatite and connective tissue growth factor derived osteoinductive peptide enhanced osteogenesis

Ruodan Xu, Zhongyang Zhang, Mette Steen Toftdal, Anne Christine Møller, Frederik Dagnaes-Hansen, Mingdong Dong, Jesper Skovhus Thomsen, Annemarie Brüel, Menglin Chen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

40 Citations (Scopus)

Abstract

In bone tissue engineering, electrospun fibrous scaffolds can provide excellent mechanical support, extracellular matrix mimicking components, such as 3D spacial fibrous environment for cell growth and controlled release of signaling molecules for osteogenesis. Here, a facile strategy comprising the incorporation of an osteogenic inductive peptide H1, derived from the cysteine knot (CT) domain of connective tissue growth factor (CTGF), in the core of Silk Fibroin (SF) was developed for osteogenic induction, synergistically with co-delivering hydroxyapatite (HA) from the shell of poly(l-lactic acid-co-ε-caprolactone) (PLCL). The core-shell nanofibrous structure was confirmed by transmission electron microscopy (TEM). Furthermore, the sustained released H1 has effectively promoted proliferation and osteoblastic differentiation of human induced pluripotent stem cells-derived mesenchymal stem cells (hiPS-MSCs). Moreover, after 8 weeks implantation in mice, this SF-H1/PLCL-HA composite induced bone tissue formation significantly faster than SF/PLCL as indicated by μCT. The present study is the first to demonstrate that release of short hydrophilic peptides derived from CTGF combined with HA potentiated the regenerative capacity for healing critical sized calvarial defect in vivo.

Original languageEnglish
JournalJournal of Controlled Release
Volume301
Pages (from-to)129-139
Number of pages11
ISSN0168-3659
DOIs
Publication statusPublished - 2019

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