Improvement of osteogenic differentiation of human mesenchymal stem cells on composite poly l-lactic acid/nano-hydroxyapatite scaffolds for bone defect repair

Angela De Luca, Ilenia Vitrano, Viviana Costa, Lavinia Raimondi, Valeria Carina, Daniele Bellavia, Gioacchino Conoscenti, Rossella Di Falco, Francesco Carfì Pavia, Vincenzo La Carrubba, Valerio Brucato, Gianluca Giavaresi

Research output: Contribution to journalArticle

Abstract

Tissue engineering offers new approaches to repair bone defects, which cannot be repaired physiologically, developing scaffolds that mimic bone tissue architecture. Furthermore, biomechanical stimulation induced by bioreactor, provides biomechanical cues that regulate a wide range of cellular events especially required for cellular differentiation and function. The improvement of human mesenchymal stem cells (hMSCs) colonization in poly-l-lactic-acid (PLLA)/nano-hydroxyapatite (nHA) composite scaffold was evaluated in terms of cell proliferation (dsDNA content), bone differentiation (gene expression and protein synthesis) and ultrastructural analysis by comparing static (s3D) and dynamic (d3D) 3D culture conditions at 7 and 21 days. The colonization rate of hMSCs and osteogenic differentiation were amplified by d3D when physical stimulation was provided by a perfusion bioreactor. Increase in dsDNA content (p < 0.0005), up-regulation of RUNX2, ALPL, SPP1 (p < 0.0005) and SOX9 (p < 0.005) gene expression, and more calcium nodule formation (p < 0.0005) were observed in d3D cultures in comparison to s3D ones over time. Dynamic 3D culture, mimicking the mechanical signals of bone environment, improved significantly osteogenic differentiation of hMSCs on PLLA/nHA scaffold, without the addition of growth factors, confirming this composite scaffold suitable for bone regeneration.

Original languageEnglish
Pages (from-to)250-257
Number of pages8
JournalJournal of Bioscience and Bioengineering
Volume129
Issue number2
DOIs
Publication statusPublished - Feb 2020

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Keywords

  • 3D culture
  • Bioreactor
  • Composite scaffold
  • Osteogenic differentiation w/o growth factors
  • Poly-l-lactic-acid/nano-hydroxyapatite

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