Tissue engineering typically uses a combination of biomaterial scaffolds, cells and signaling mechanisms (such as growth factors or mechanical stimuli) to restore the function of damaged or degenerated tissues. The research carried out in our laboratory investigates each of these three areas with target applications in tissues including bone, cartilage, skin, cardiovascular, respiratory, and neural tissues. Our research always maintains a translational focus and a number of regenerative scaffold technologies have been translated to the clinic through spin-out formation and licensing to industry. A major focus of ongoing research has been to functionalise these scaffolds for use as delivery systems for biomolecules such as growth factors to enhance their therapeutic potential. However, controlling the release of these factors in order to maximise efficacy while limiting aberrent side effects is a major challenge and has proved increasingly problematic in successful clinical translation. Gene therapy might be a valuable tool to avoid the limitations of local delivery of growth factors.
The COVID-19 pandemic has shown how revolutionary treatments based on gene therapeutics has helped overcome a once-in-a-century pandemic and has given new momentum to gene therapy research for a myriad of applications. The field of regenerative medicine is well placed to be a beneficiary whereby, for example, gene therapy might be a valuable tool to avoid the limitations of local delivery of growth factors. While non-viral vectors are typically inefficient at transfecting cells, our group have had significant success in this area using a scaffold-mediated gene therapy approach for regenerative applications[1, 2]. These gene activated scaffold platforms not only act as a template for cell infiltration and tissue formation, but also can be engineered to direct autologous host cells to take up specific genes and then produce therapeutic proteins in a sustained but eventually transient fashion. Similarly, we have demonstrated how scaffold-mediated delivery of siRNAs[3] and miRNA[4, 5] can be used to silence specific genes associated with reduced repair or pathological states.
This presentation will provide an overview of ongoing research in our lab in this area with a particular focus on gene-activated biomaterials for promoting bone, cartilage and joint repair. Focus will also be placed on advances we are making in using 3D printing of gene activated bioinks to produce next generation medical devices for tissue repair.
1. Raftery, R.M., et al., Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives. Adv Mater, 2016. 28(27): p. 5447-69.
2. Curtin, C.M., et al., Innovative collagen nano-hydroxyapatite scaffolds offer a highly efficient non-viral gene delivery platform for stem cell-mediated bone formation. Advanced Materials, 2012. 24(6): p. 749-754.
3. Yan, L.P., et al., Collagen/GAG scaffolds activated by RALA-siMMP-9 complexes with potential for improved diabetic foot ulcer healing. Mater Sci Eng C Mater Biol Appl, 2020. 114: p. 111022.
4. Castaño, I.M., et al., Rapid bone repair with the recruitment of CD206(+)M2-like macrophages using non-viral scaffold-mediated miR-133a inhibition of host cells. Acta Biomater, 2020. 109: p. 267-279.
5. Mencia Castano, I., et al., A novel collagen-nanohydroxyapatite microRNA-activated scaffold for tissue engineering applications capable of efficient delivery of both miR-mimics and antagomiRs to human mesenchymal stem cells. Journal of Controlled Release 2015. 200: p. 42-51.
European Research Council Advanced Grant, ReCaP (agreement n° 788753)