4.8 Article

Instructive Nanofibrous Scaffold Comprising Runt-Related Transcription Factor 2 Gene Delivery for Bone Tissue Engineering

Journal

ACS NANO
Volume 8, Issue 8, Pages 8082-8094

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/nn5021049

Keywords

liposomes; mesenchymal stem cells; polycaprolactone; gene expression; scaffold; bone tissue engineering

Funding

  1. Portuguese Foundation for Science and Technology [SFRH/BD/62465/2009, SFRH/BPD/70669/2010]
  2. OsteoGraphy project [PTDC/EME-MFE/2008]
  3. POLARIS [FP7-REGPOT-2012-2013-1]
  4. MaxBone [PTDC/SAU -ENB/115179/2009]
  5. North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF) projects
  6. [RL3-TECT-NORTE-01-0124-FEDER-000020]
  7. Fundação para a Ciência e a Tecnologia [SFRH/BD/62465/2009, PTDC/SAU-ENB/115179/2009] Funding Source: FCT

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Inducer molecules capable of regulating mesenchymal stem cell differentiation into specific lineages have proven effective in basic science and in preclinical studies. Runt related transcription factor 2 (RUNX2) is considered to be the central gene involved in the osteoblast phenotype induction, which may be advantageous for inducing bone tissue regeneration. This work envisions the development of a platform for gene delivery, combining liposomes as gene delivery devices, with electrospun nanofiber mesh (NFM) as a tissue engineering scaffold pDNA-loaded liposomes were immobilized at the surface of functionalized polycaprolactone (PCL) NFM. Human bone-marrow-derived mesenchymal stem cells (hBMSCs) cultured on RUNX2-loaded liposomes immobilized at the surface of electrospun PCL NFM showed enhanced levels of metabolic activity and total protein synthesis. RUNX2-loaded liposomes immobilized at the surface of electrospun PCL. NFMs induce a long-term gene expression of eGFP and RUNX2 by cultured hBMSCs. Furthermore, osteogenic differentiation of hBMSCs was also achieved by the overexpression of other osteogenic markers in medium free of osteogenic supplementation. These findings demonstrate that surface immobilization of RUNX2 plasmid onto elestrospun PCL NFM can produce long-term gene expression in vitro, which may be employed to enhance the osteoinductive properties of scaffolds used for bone tissue engineering strategies.

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