Nanolayered hybrid mediates synergistic co-delivery of ligand and ligation activator for inducing stem cell differentiation and tissue healing

Heemin Kang, Minkyu Kim, Qian Feng, Sien Lin, Kongchang Wei, Rui Li, Chan Ju Choi, Tae Hyun Kim, Gang Li, Jae Min Oh, Liming Bian

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Cellular behaviors, such as differentiation, are regulated by complex ligation processes involving cell surface receptors, which can be activated by various divalent metal cations. The design of nanoparticle for co-delivery of ligand and ligation activator can offer a novel strategy to synergistically stimulate ligation processes in vivo. Here, we present a novel layered double hydroxide (LDH)-based nanohybrid (MgFe-Ado-LDH), composed of layered MgFe hydroxide nanocarriers sandwiching the adenosine cargo molecule, maintained through an electrostatic balance, to co-deliver the adenosine (Ado) ligand from the interlayer spacing and the Mg2+ ion (ligation activator) through the dissolution of the MgFe nanocarrier itself. Our findings demonstrate that the MgFe-Ado-LDH nanohybrid promoted osteogenic differentiation of stem cells through the synergistic activation of adenosine A2b receptor (A2bR) by the dual delivery of adenosine and Mg2+ ions, outperforming direct supplementation of adenosine alone. Furthermore, the injection of the MgFe-Ado-LDH nanohybrid and stem cells embedded within hydrogels promoted the healing of rat tibial bone defects through the rapid formation of fully integrated neo-bone tissue through the activation of A2bR. The newly formed bone tissue displayed the key features of native bone, including calcification, mature tissue morphology, and vascularization. This study demonstrates a novel and effective strategy of bifunctional nanocarrier-mediated delivery of ligand (cargo molecule) and activation of its ligation to receptor by the nanocarrier itself for synergistically inducing stem cell differentiation and tissue healing in vivo, thus offering novel design of biomaterials for regenerative medicine.

Original languageEnglish
Pages (from-to)12-28
Number of pages17
JournalBiomaterials
Volume149
DOIs
Publication statusPublished - 2017 Dec
Externally publishedYes

Bibliographical note

Funding Information:
Project 31570979 is supported by the National Natural Science Foundation of China . The work described in this paper is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project no. 14202215 , 14220716 ). This work is supported by the Health and Medical Research Fund , the Food and Health Bureau , the Government of the Hong Kong Special Administrative Region (reference no.: 04152836 , 03140056 ). This research was also supported by the project BME-p3-15 of the Shun Hing Institute of Advanced Engineering , The Chinese University of Hong Kong . This research is supported by the Chow Yuk Ho Technology Centre for Innovative Medicine , The Chinese University of Hong Kong . This study was supported by the Ministry of Trade, Industry and Energy (MOTIE, Korea) under Industrial Technology Innovation Program. No. 10062252 , “Development of antibiofouling functional tracheostomy tube component for critical patients”. Appendix A

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

  • Ligation activator
  • Minimally invasive surgery
  • Nanohybrid
  • Stem cell differentiation
  • Synergistic ligation
  • Tissue repair

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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