To date, we have successfully characterised the pre- and post-iPS skin cells ("fibroblasts") and demonstrated differences in the matrix produced by the post-iPS cells. The post-iPS cells produced more matrix, and certain proteins produced are consistent with a younger type of matrix, including a factor that promotes blood vessel growth. Next, we developed techniques to convert this matrix into a new wound healing device. These scaffolds could be seeded with normal and diabetic foot ulcer fibroblasts, supporting their growth, and producing a wide variety of matrix proteins, which are conducive to wound healing. Furthermore, the cells produced more of a protein associated with new blood vessel growth. Finally, the scaffolds had a favourable immune response, enabling the immune system to direct whether an anti- or pro-inflammatory environment was created, which is beneficial for wound healing which requires both phases as healing progresses.
The on-demand delivery system was successfully adapted for releasing genes at specific timepoints. However, to fully enhance their activity, further optimisation is required. In parallel, we developed an alternative, more stable, DNA-based nanoparticle, which we could successfully release and demonstrated its bioactivity. This nanoparticle could be loaded with chemotherapeutic drugs and was capable of limiting cancer cell growth in vitro.
Ultimately, we believe the two systems need to be combined together to form an effective wound healing device. Thus, we have developed two versions of the device. In the first, the on-demand delivery system is integrated throughout the scaffold. We demonstrated its ability to release nanoparticles on demand within the scaffold. In the second version, we incorporated the drug delivery device in discrete locations within the scaffold. This enables the operator to release different drugs at different timepoints by targeting the discrete areas.
