Abstract

The development of a new family of implantable bioinspired materials is a focal point of bone tissue engineering. Implant surfaces that better mimic the natural bone extracellular matrix, a naturally nano-composite tissue, can stimulate stem cell differentiation towards osteogenic lineages in the absence of specific chemical treatments. Herein we describe a bioactive composite nanofibrous scaffold, composed of poly-caprolactone (PCL) and nano-sized hydroxyapatite (HA) or beta-tricalcium phosphate (TCP), which was able to support the growth of human bone marrow mesenchymal stem cells (hMSCs) and guide their osteogenic differentiation at the same time. Morphological and physical/chemical investigations were carried out by scanning, transmission electron microscopy, Fourier-transform infrared (FTIR) spectroscopy, mechanical and wettability analysis. Upon culturing hMSCs on composite nanofibers, we found that the incorporation of either HA or TCP into the PCL nanofibers did not affect cell viability, meanwhile the presence of the mineral phase increases the activity of alkaline phosphatase (ALP), an early marker of bone formation, and mRNA expression levels of osteoblast-related genes, such as the Runt-related transcription factor 2 (Runx-2) and bone sialoprotein (BSP), in total absence of osteogenic supplements. These results suggest that both the nanofibrous structure and the chemical composition of the scaffolds play a role in regulating the osteogenic differentiation of hMSCs.

Highlights

  • Regenerative medicine aims to repair and replace lost or damaged tissues by initiating the natural regeneration process

  • Scaffolds characterization In this study, we demonstrate that a composite nanofibrous scaffold alone can induce a significant modification of osteogenic markers, suggesting the induction into osteogenic lineage, of human bone marrow mesenchymal stem cells (hMSCs)

  • Higher concentrations of nanoparticles in the composite solution unavoidably led to beads formation due to particles agglomeration, as noted using a 3.5% PCL 4% HA solution

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Summary

Introduction

Regenerative medicine aims to repair and replace lost or damaged tissues by initiating the natural regeneration process. The scaffold design is aimed at reproducing all required signals at macro, micro- to nano-scales, respectively corresponding to tissue, cellular, and molecular scales in a specific tissue, in order to foster and direct cellular attachment, proliferation, desired differentiation towards specific cell phenotypes. In this context, several factors must be considered, such as the chemical nature of scaffolding material, the physical structures at various size scales, and the method of fabrication [2,3,4,5,6]. A good compromise may be represented by composites joining polymer plasticity with the osteoinductivity of phosphate ceramics

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