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Engineered Scaffolds for the Delivery of Gene Therapeutics for Enhanced Tissue Repair

ABSTRACT

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, nerve and wound 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. 

 

Acknowledgements: European Research Council Advanced Grant, ReCaP (agreement n° 788753)

References:

  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 : official journal of the Controlled Release Society, 2015. 200: p. 42-51.

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