Microcarriers Based on Glycosaminoglycan-Like Marine Exopolysaccharide for TGF-β1 Long-Term Protection

Mar Drugs. 2019 Jan 19;17(1):65. doi: 10.3390/md17010065.

Abstract

Articular cartilage is an avascular, non-innervated connective tissue with limited ability to regenerate. Articular degenerative processes arising from trauma, inflammation or due to aging are thus irreversible and may induce the loss of the joint function. To repair cartilaginous defects, tissue engineering approaches are under intense development. Association of cells and signalling proteins, such as growth factors, with biocompatible hydrogel matrix may lead to the regeneration of the healthy tissue. One current strategy to enhance both growth factor bioactivity and bioavailability is based on the delivery of these signalling proteins in microcarriers. In this context, the aim of the present study was to develop microcarriers by encapsulating Transforming Growth Factor-β1 (TGF-β1) into microparticles based on marine exopolysaccharide (EPS), namely GY785 EPS, for further applications in cartilage engineering. Using a capillary microfluidic approach, two microcarriers were prepared. The growth factor was either encapsulated directly within the microparticles based on slightly sulphated derivative or complexed firstly with the highly sulphated derivative before being incorporated within the microparticles. TGF-β1 release, studied under in vitro model conditions, revealed that the majority of the growth factor was retained inside the microparticles. Bioactivity of released TGF-β1 was particularly enhanced in the presence of highly sulphated derivative. It comes out from this study that GY785 EPS based microcarriers may constitute TGF-β1 reservoirs spatially retaining the growth factor for a variety of tissue engineering applications and in particular cartilage regeneration, where the growth factor needs to remain in the target location long enough to induce robust regenerative responses.

Keywords: bioactivity; exopolysaccharide; growth factor; microfluidics; microparticles.

MeSH terms

  • Alteromonas / chemistry*
  • Biological Availability
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / physiology
  • Cell Line
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Carriers / chemistry*
  • Drug Carriers / isolation & purification
  • Drug Compounding / methods
  • Drug Implants
  • Drug Liberation
  • Humans
  • Hydrothermal Vents / microbiology
  • Microfluidics
  • Polysaccharides / chemistry*
  • Polysaccharides / isolation & purification
  • Regeneration / drug effects
  • Tissue Scaffolds / chemistry
  • Transforming Growth Factor beta1 / administration & dosage*
  • Transforming Growth Factor beta1 / pharmacokinetics

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Drug Implants
  • GY785 DR
  • GY785 DRS
  • Polysaccharides
  • Transforming Growth Factor beta1