Multifunctional Scaffolds with Improved Antimicrobial Properties and Osteogenicity Based on Piezoelectric Electrospun Fibers Decorated with Bioactive Composite Microcapsules

ACS Appl Mater Interfaces. 2018 Oct 17;10(41):34849-34868. doi: 10.1021/acsami.8b09810. Epub 2018 Oct 3.

Abstract

The incorporation of bioactive compounds onto polymer fibrous scaffolds with further control of drug release kinetics is essential to improve the functionality of scaffolds for personalized drug therapy and regenerative medicine. In this study, polymer and hybrid microcapsules were prepared and used as drug carriers, which are further deposited onto polymer microfiber scaffolds [polycaprolactone (PCL), poly(3-hydroxybutyrate) (PHB), and PHB doping with the conductive polyaniline (PANi) of 2 wt % (PHB-PANi)]. The number of immobilized microcapsules decreased with increase in their ζ-potential due to electrostatic repulsion with the negatively charged fiber surface, depending on the polymer used for the scaffold's fabrication. Additionally, the immobilization of the capsules in dynamic mechanical conditions at a frequency of 10 Hz resulted in an increase in the number of the capsules on the fibers with increase in the scaffold piezoelectric response in the order PCL < PHB < PHB-PANi, depending on the chemical composition of the capsules. The immobilization of microcapsules loaded with different bioactive molecules onto the scaffold surface enabled multimodal triggering by physical (ultrasound, laser radiation) and biological (enzymatic treatment) stimuli, providing controllable release of the cargo from scaffolds. Importantly, the microcapsules immobilized onto the surface of the scaffolds did not influence the cell growth, viability, and cell proliferation on the scaffolds. Moreover, the attachment of human mesenchymal stem cells (hMSCs) on the scaffolds revealed that the PHB and PHB-PANi scaffolds promoted adhesion of hMSCs compared to that of the PCL scaffolds. Two bioactive compounds, antibiotic ceftriaxone sodium (CS) and osteogenic factor dexamethasone (DEXA), were chosen to load the microcapsules and demonstrate the antimicrobial properties and osteogenesis of the scaffolds. The modified scaffolds had prolonged release of CS or DEXA, which provided an improved antimicrobial effect, as well as enhanced osteogenic differentiation and mineralization of the scaffolds modified with capsules compared to that of individual scaffolds soaked in CS solution or incubated in an osteogenic medium. Thus, the immobilization of microcapsules provides a simple, convenient way to incorporate bioactive compounds onto polymer scaffolds, which makes these multimodal materials suitable for personalized drug therapy and bone tissue engineering.

Keywords: antibacterial properties; cell adhesion; osteogenic differentiation; polyelectrolyte and hybrid microcapsules; polymer scaffolds; sol−gel coating.

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Capsules
  • Ceftriaxone* / chemistry
  • Ceftriaxone* / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Osteogenesis / drug effects*
  • Polyesters / chemistry
  • Polyesters / pharmacology
  • Prohibitins
  • Tissue Scaffolds / chemistry*

Substances

  • Anti-Bacterial Agents
  • Capsules
  • PHB protein, human
  • Polyesters
  • Prohibitins
  • polycaprolactone
  • Ceftriaxone