VEGF delivery by smart polymeric PNIPAM nanoparticles affects both osteogenic and angiogenic capacities of human bone marrow stem cells

Afsaneh Adibfar, Ghassem Amoabediny*, Mohamadreza Baghaban Eslaminejad, Javad Mohamadi, Fatemeh Bagheri, Behrouz Zandieh Doulabi

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Objective: Bone tissue engineering (BTE) faces a major challenge with cell viability after implantation of a construct due to lack of functional vasculature within the implant. Human bone marrow derived mesenchymal stem cells (hBMSCs) have the potential to undergo transdifferentiation towards an endothelial cell phenotype, which may be appropriate for BTE in conjunction with the appropriate scaffolds and microenvironment. Hypothesis and methods: We hypothesized that slow delivery of vascular endothelial growth factor (VEGF) by using nanoparticles in combination with osteogenic stimuli might enhance both osteogenic and angiogenic differentiation of angiogenic primed hBMSCs cultured in an osteogenic microenvironment. Therefore, we developed a new strategy to enhance vascularization in BTE in vitro by synthesis of smart temperature sensitive poly(N‑isopropylacrylamide) (PNIPAM) nanoparticles. We used PNIPAM nanoparticles loaded with collagen to investigate their ability to deliver VEGF for both angiogenic and osteogenic differentiation. Results: We used the free radical polymerization technique to synthesize PNIPAM nanoparticles, which had particle sizes of approximately 100 nm at 37 °C and LCST of 30–32 °C. The cumulative VEGF release after 72 h for VEGF loaded PNIPAM (VEGF-PNIPAM) nanoparticles was 70%; for VEGF-PNIPAM loaded collagen hydrogels, it was 23%, which indicated slower release of VEGF in the VEGF-PNIPAM loaded collagen system. Immunocytochemistry (ICC) and inverted microscope visualization confirmed endothelial differentiation and capillary-like tube formation in the osteogenic culture medium after 14 days. Quantitative real-time polymerase chain reaction (QRT-PCR) also confirmed expressions of collagen type I (Col I), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN) osteogenic markers along with expressions of platelet-endothelial cell adhesion molecule-1 (CD31), von Willebrand factor (vWF), and kinase insert domain receptor (KDR) angiogenic markers. Our data clearly showed that VEGF released from PNIPAM nanoparticles and VEGF-PNIPAM loaded collagen hydrogel could significantly contribute to the quality of engineered bone tissue.

Original languageEnglish
Pages (from-to)790-799
Number of pages10
JournalMaterials Science and Engineering C
Volume93
DOIs
Publication statusPublished - 1 Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Angiogenesis
  • Growth factor delivery
  • Temperature-responsive PNIPAM nanoparticles
  • Vascular bone tissue engineering

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