Synergistic effect of bimodal pore distribution and artificial extracellular matrices in polymeric scaffolds on osteogenic differentiation of human mesenchymal stem cells

Mater Sci Eng C Mater Biol Appl. 2019 Apr;97:12-22. doi: 10.1016/j.msec.2018.12.012. Epub 2018 Dec 7.


The main objective of this study was to enhance the biological performance of resorbable polymeric scaffolds for bone tissue engineering. Specifically, we focused on both microstructure and surface modification of the scaffolds to augment adhesion, proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSC). Moreover, a new cell seeding method assuring 90% seeding efficiency on the scaffolds was developed. Poly(l‑lactide‑co‑glycolide) (PLGA) scaffolds with monomodal and bimodal pore distribution were produced by solvent casting/phase separation followed by porogen leaching and modified with artificial extracellular matrices (aECM) consisting of collagen type I and high sulphated hyaluronan (sHya). The application of two porogens resulted in bimodal pore distribution within the PLGA scaffolds as shown by scanning electron microscopy and microcomputer tomography. Two types of pores with diameters 400-600 μm and 2-20 μm were obtained. The scaffolds were successfully coated with a homogenous layer of aECM as shown by Sirius red and toluidine blue staining. In vitro study showed that presence of bimodal pore distribution in combination with collagen/sHya did not significantly influence hMSC proliferation and early osteogenic differentiation compared to scaffolds with monomodal pore distribution. However, it enhanced mineralization as well as the expression of Runt-related transcription factor 2, osteopontin and bone sialoprotein II. As a result PLGA scaffolds with bimodal pore distribution modified with collagen/sHya can be considered as prospective material promoting bone regeneration.

Keywords: Artificial extracellular matrices; Bimodal porosity; Bone tissue engineering scaffolds; Human mesenchymal stem cells; Osteogenic differentiation; Poly(l‑lactide‑co‑glycolide).

MeSH terms

  • Adult
  • Calcium Phosphates / metabolism
  • Cell Adhesion
  • Cell Differentiation / physiology*
  • Cell Proliferation
  • Collagen Type I / chemistry
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Extracellular Matrix
  • Humans
  • Hyaluronic Acid / chemistry
  • Integrin-Binding Sialoprotein / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / physiology
  • Microscopy, Electron, Scanning
  • Osteogenesis
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Tissue Engineering / methods
  • Tissue Scaffolds*


  • Calcium Phosphates
  • Collagen Type I
  • Core Binding Factor Alpha 1 Subunit
  • Integrin-Binding Sialoprotein
  • RUNX2 protein, human
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Hyaluronic Acid
  • calcium phosphate