Enhancing osteoconduction of PLLA-based nanocomposite scaffolds for bone regeneration using different biomimetic signals to MSCs

Int J Mol Sci. 2012;13(2):2439-2458. doi: 10.3390/ijms13022439. Epub 2012 Feb 22.

Abstract

In bone engineering, the adhesion, proliferation and differentiation of mesenchymal stromal cells rely on signaling from chemico-physical structure of the substrate, therefore prompting the design of mimetic "extracellular matrix"-like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA)-based scaffolds have been mixed with different components, including single walled carbon nanotubes (CNT), micro-hydroxyapatite particles (HA), and BMP2, and treated with plasma (PT), to obtain four different nanocomposites: PLLA + CNT, PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow mesenchymal stromal cells (MSCs) were derived from the femur of orthopaedic patients, seeded on the scaffolds and cultured under osteogenic induction up to differentiation and mineralization. The release of specific metabolites and temporal gene expression profiles of marrow-derived osteoprogenitors were analyzed at definite time points, relevant to in vitro culture as well as in vivo differentiation. As a result, the role of the different biomimetic components added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the highest biomimetic activity on cells differentiating to mature osteoblasts. The modification of a polymeric scaffold with reinforcing components which also work as biomimetic cues for cells can effectively direct osteoprogenitor cells differentiation, so as to shorten the time required for mineralization.

Keywords: biomimetic nanocomposites; bone tissue engineering; mesenchymal stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology
  • Bone Regeneration* / drug effects
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Guided Tissue Regeneration / instrumentation
  • Guided Tissue Regeneration / methods
  • Humans
  • Lactic Acid / chemistry*
  • Lactic Acid / pharmacology
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology
  • Middle Aged
  • Nanocomposites / chemistry*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / physiology
  • Osteogenesis / drug effects
  • Polyesters
  • Polymers / chemistry*
  • Polymers / pharmacology
  • Signal Transduction / drug effects
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*

Substances

  • Polyesters
  • Polymers
  • Lactic Acid
  • poly(lactide)