3D bioprinted scaffolds for diabetic wound-healing applications

Abstract

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU.

Keywords: Bioprinting; Diabetes mellitus; Diabetic foot ulcer; Drug delivery; Levofloxacin; Wound healing.

Fig. 1

Schematics showing a extrusion-based, b inkjet-based, and c laser-assisted bioprinting technologies

Fig. 2

Chemical structure of levofloxacin

Fig. 3

Digital images showing honeycomb (a), square (b), parallel (c), triangular (d), double-parallel (e), and the flexibility of a bioprinted PCL scaffold (f)

Fig. 4

SEM micrographs of PCL control scaffolds, showing honeycomb (a), square (b), parallel (c), triangular (d), double-parallel (e), and a 3.0% LFX-loaded scaffold (f). All images were taken at × 50 magnification

Fig. 5

ATR-FTIR spectra showing a a comparison of PC powder prior to the 3D bioprinting process and printed PCL and b a comparison of pure LFX powder prior to the 3D bioprinting process and 0.5%, 1.5%, and 3.0% LFX-loaded formulations following printing

Fig. 6

Graphs showing a TGA profiles of LFX powder, PCL control, and PCL loaded with 0.5% and 3.0% LFX; b DSC traces of LFX powder, 0.5% LFX and 3.0% LFX; and c DSC traces of PCL powder and printed PCL

Fig. 7

Force/displacement graphs for honeycomb design, parallel, square, and double-parallel control designs

Fig. 8

Graph showing the effect of the percentage LFX loading into PCL scaffold on their elastic modulus

Fig. 9

Graph showing (a) cumulative in vitro drug release profile of LFX from drug-loaded scaffolds of varying concentrations (n = 3) and (b) percentage drug release profile of LFX from drug-loaded scaffolds with varying LFX loadings (n = 3)

Fig. 10

Diameter of the zone of inhibition of S. aureus and E. coli with 0.5% and 1.5% levofloxacin-loaded scaffolds