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 journalArticle

5 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 1
Externally publishedYes

Fingerprint

Stem cells
Adenosine
Ligation
Cell Differentiation
Bone
Stem Cells
Ligands
Tissue
Chemical activation
Bone and Bones
Molecules
Ions
Biomaterials
Hydrogels
Rats
Electrostatics
Dissolution
Positive ions
Purinergic P1 Receptors
Regenerative Medicine

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

Cite this

Nanolayered hybrid mediates synergistic co-delivery of ligand and ligation activator for inducing stem cell differentiation and tissue healing. / Kang, Heemin; Kim, Minkyu; Feng, Qian; Lin, Sien; Wei, Kongchang; Li, Rui; Choi, Chan Ju; Kim, Tae Hyun; Li, Gang; Oh, Jae Min; Bian, Liming.

In: Biomaterials, Vol. 149, 01.12.2017, p. 12-28.

Research output: Contribution to journalArticle

Kang, Heemin ; Kim, Minkyu ; Feng, Qian ; Lin, Sien ; Wei, Kongchang ; Li, Rui ; Choi, Chan Ju ; Kim, Tae Hyun ; Li, Gang ; Oh, Jae Min ; Bian, Liming. / Nanolayered hybrid mediates synergistic co-delivery of ligand and ligation activator for inducing stem cell differentiation and tissue healing. In: Biomaterials. 2017 ; Vol. 149. pp. 12-28.
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AU - Kim, Minkyu

AU - Feng, Qian

AU - Lin, Sien

AU - Wei, Kongchang

AU - Li, Rui

AU - Choi, Chan Ju

AU - Kim, Tae Hyun

AU - Li, Gang

AU - Oh, Jae Min

AU - Bian, Liming

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AB - 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.

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KW - Synergistic ligation

KW - Tissue repair

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