Novel biodegradable fibres for applications in tissue engineering and drug delivery

  • Matthew R. Williamson

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

The preparation and characterisation of novel biodegradable polymer fibres for application in tissue engineering and drug delivery are reported. Poly(e-caprolactone) (PCL) fibres were produced by wet spinning from solutions in acetone under low shear (gravity flow) conditions. The tensile strength and stiffness of as-spun fibres were highly dependent on the concentration of the spinning solution. Use of a 6% w/v solution resulted in fibres having strength and stiffness of 1.8 MPa and 0.01 GPa respectively, whereas these values increased to 9.9 MPa and 0.1 GPa when fibres were produced from 20% w/v solutions. Cold drawing to an extension of 500% resulted in further increases in fibre strength (up to 50 MPa) and stiffness (0.3 GPa). Hot drawing to 500% further increased the fibre strength (up to 81 MPa) and stiffness (0.5 GPa). The surface morphology of as-spun fibres was modified, to yield a directional grooved pattern by drying in contact with a mandrel having a machined topography characterised by a peak-peak separation of 91 mm and a peak height of 30 mm. Differential scanning calorimetery (DSC) analysis of as-spun fibres revealed the characteristic melting point of PCL at around 58°C and a % crystallinity of approximately 60%. The biocompatibility of as-spun fibres was assessed using cell culture.
The number of attached 3T3 Swiss mouse fibroblasts, C2C12 mouse myoblasts and human umbilical vein endothelial cells (HUVECs) on as-spun, 500% cold drawn, and gelatin coated PCL fibres were observed. The results showed that the fibres promoted cell proliferation for 9 days in cell culture and was slightly lower than on tissue culture plastic. The morphology of all cell lines was assessed on the various PCL fibres using scanning electron microscopy. The cell function of HUVECs growing on the as-spun PCL fibres was evaluated. The ability HUVECs to induce an immune response when stimulated with lipopolysaccaride (LPS) and thereby to increase the amount of cell surface receptors was assessed by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that PCL fibres did not inhibit this function compared to TCP.
As-spun PCL fibres were loaded with 1 % ovine albumin (OVA) powder, 1% OVA
nanoparticles and 5% OVA nanoparticles by weight and the protein release was
assessed in vitro. PCL fibres loaded with 1 % OVA powder released 70%, 1% OVA
nanoparticle released 60% and the 5% OVA nanoparticle released 25% of their
protein content over 28 days. These release figures did not alter when the fibres were subjected to lipase enzymatic degradation. The OVA released was examined for structural integrity by SDS-PAGE. This showed that the protein molecular weight was not altered after incorporation into the fibres.
The bioactivity of progesterone was assessed following incorporation into PCL fibres.
Results showed that the progesterone released had a pronounced effect on MCF-7 breast epithelial cells, inhibiting their proliferation.
The PCL fibres display high fibre compliance, a potential for controlling the fibre
surface architecture to promote contact guidance effects, favorable proliferation rate of fibroblasts, myoblasts and HUVECs and the ability to release pharmaceuticals. These properties recommended their use for 3-D scaffold production in soft tissue engineering and the fibres could also be exploited for controlled presentation and release of biopharmaceuticals such as growth factors.
Date of AwardMay 2003
LanguageEnglish
SupervisorAllan G.A. Coombes (Supervisor), Eric F Adams (Supervisor) & Helen R Griffiths (Supervisor)

Keywords

  • Novel biodegradable fibres
  • applications
  • tissue engineering
  • drug delivery

Cite this

Novel biodegradable fibres for applications in tissue engineering and drug delivery
Williamson, M. R. (Author). May 2003

Student thesis: Doctoral ThesisDoctor of Philosophy