A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

J Biomater Sci Polym Ed. 2017 Nov;28(16):1966-1983. doi: 10.1080/09205063.2017.1364100. Epub 2017 Aug 17.

Abstract

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

Keywords: BMPs: bone morphogenetic proteins; BSA: bovine serum albumin; DCM: dichloromethane; DMSO: dimethyl sulphoxide; ECM: extracellular matrix; FTIR: Fourier transform infrared; PBS: phosphate-buffered saline; PLGA: poly (lactic-co-glycolic acid); PVA: poly (vinyl alcohol); Polymeric biomaterials; SDS: sodium dodecyl sulphate; SEM: scanning electron microscopy; TPP: sodium tripolyphosphate; ToF-SIMS: time of flight secondary ion mass spectroscopy; controlled delivery; formulation; hMSC: primary human mesenchymal stem cells; mechanical properties; microspheres; poly (lactic-co-glycolic acid) (PLGA); protein delivery; tissue engineering.

MeSH terms

  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / metabolism
  • Biocompatible Materials / pharmacology*
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone and Bones / cytology*
  • Calcification, Physiologic / drug effects
  • Cell Proliferation / drug effects
  • Chitosan / chemistry*
  • Humans
  • Injections
  • Kinetics
  • Lactic Acid / chemistry*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Microspheres
  • Osteocalcin / metabolism
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Serum Albumin, Bovine / metabolism
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry*

Substances

  • Biocompatible Materials
  • Bone Morphogenetic Protein 2
  • Osteocalcin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Serum Albumin, Bovine
  • Lactic Acid
  • Chitosan