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
JournalJournal of Bioscience and Bioengineering
DOIs
Publication statusE-pub ahead of print - Sep 7 2019

Fingerprint

Durapatite
Lactic acid
Scaffolds (biology)
Stem cells
Mesenchymal Stromal Cells
Hydroxyapatite
Lactic Acid
Bone
Repair
Bone and Bones
Defects
Scaffolds
Composite materials
Bioreactors
Physical Stimulation
Gene expression
Gene Expression
Bone Regeneration
Tissue Engineering
Cues

Keywords

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

Cite this

Improvement of osteogenic differentiation of human mesenchymal stem cells on composite poly l-lactic acid/nano-hydroxyapatite scaffolds for bone defect repair. / De Luca, Angela; Vitrano, Ilenia; Costa, Viviana; Raimondi, Lavinia; Carina, Valeria; Bellavia, Daniele; Conoscenti, Gioacchino; Di Falco, Rossella; Pavia, Francesco Carfì; La Carrubba, Vincenzo; Brucato, Valerio; Giavaresi, Gianluca.

In: Journal of Bioscience and Bioengineering, 07.09.2019.

Research output: Contribution to journalArticle

De Luca, Angela ; Vitrano, Ilenia ; Costa, Viviana ; Raimondi, Lavinia ; Carina, Valeria ; Bellavia, Daniele ; Conoscenti, Gioacchino ; Di Falco, Rossella ; Pavia, Francesco Carfì ; La Carrubba, Vincenzo ; Brucato, Valerio ; Giavaresi, Gianluca. / Improvement of osteogenic differentiation of human mesenchymal stem cells on composite poly l-lactic acid/nano-hydroxyapatite scaffolds for bone defect repair. In: Journal of Bioscience and Bioengineering. 2019.
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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.",
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T1 - Improvement of osteogenic differentiation of human mesenchymal stem cells on composite poly l-lactic acid/nano-hydroxyapatite scaffolds for bone defect repair

AU - De Luca, Angela

AU - Vitrano, Ilenia

AU - Costa, Viviana

AU - Raimondi, Lavinia

AU - Carina, Valeria

AU - Bellavia, Daniele

AU - Conoscenti, Gioacchino

AU - Di Falco, Rossella

AU - Pavia, Francesco Carfì

AU - La Carrubba, Vincenzo

AU - Brucato, Valerio

AU - Giavaresi, Gianluca

N1 - Copyright © 2019 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

PY - 2019/9/7

Y1 - 2019/9/7

N2 - 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.

AB - 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.

KW - 3D culture

KW - Bioreactor

KW - Composite scaffold

KW - Osteogenic differentiation w/o growth factors

KW - Poly-l-lactic-acid/nano-hydroxyapatite

U2 - 10.1016/j.jbiosc.2019.08.001

DO - 10.1016/j.jbiosc.2019.08.001

M3 - Article

JO - Journal of Bioscience and Bioengineering

JF - Journal of Bioscience and Bioengineering

SN - 1389-1723

ER -