1. Composite Poly(methyl methacrylate)/Poly(ethylene glycol) electrospun nanofibrous mats as a novel wound dressing for controlled release of an anti- scarring agent Malihe-Sadat Poormasjedi-Meibod, PhD candidate Experimental medicine Burn and Wound Healing Lab, Dep. Of Surgery University of British Columbia March 16 th, 2015

2. Background-Wound healing process

3. Background-Wound healing spectrum Wound healing spectrum Normal wound healing Non-healing wounds 1.Diabetic foot ulcer 2.Pressure ulcer Post-burn hypertrophic scars 3 Skin fibrosis

4. Background-HSC current treatments 4 4

5. Background-KynA as an anti-fobrogeic agent A C 6.25 12.5 25 50 100 150 (µg/ml) β-actin Collagen-I KynA MMP1 Normal Control Vehicle 10x 2x KynA B C Poormasjedi-Meibod et al., PLOSone, 2014 **

6. Hypothesis KynA can be incorporated into nanofibers to develop anti-fibrogenic wound dressings which slowly release the drug and improve the wound healing outcome.

7. Electrospinning process and parameters PolymerPEG 1KD (W/W%) Voltage (kV) Syringe pump (mm/min) KynA (W/W%) Solvent PMMA (350 KD)0240.16DMF PMMA (350 KD)1240.16DMF PMMA (350 KD)2.5240.076DMF PMMA (350 KD)5240.076DMF PMMA (350 KD)10240.056DMF PMMA (350 KD)20240.056DMF 7 Electrospinning. Current approaches to electrospun nanofibers for tissue engineering Nae Gyune Rim et al 2013 Biomed. Mater. 8 014102 doi:10.1088/1748-6041/8/1/014102

8. SEM images of PMMA-PEG nanofibers 10% 20% 1% 2.5% 5% PEG 1K 5K 10K PMMA

9. Dressing’s hydrophobicity and wetting 9 PMMA PMMA+10%PEG A B

10. Release study in PBS, total immersion setting A 10

11. Release study is PBS, 2 chamber well setting B 11 A PBS Hydrogel NF+KynA

12. B ** Assessment of medicated mat’s cytocompatibility 12 Control NFNF+ KynA Fibroblasts C Ethidium homodimer Calcein KynA Dermal fibroblast NF+KynA DMEM media A

13. Dressing’s biological activity assessment * * ** A Col-I GAPDH ConNFNF+KynAKynA MMP1 13 B C

14. 10x 2x A NormalControlNFNF+KynAKynA cream 14 KynA-loaded dressings reduces skin fibrosis ** A NF+KynA KynA cream ** B Nor Con NF NF+KynA KynA cream

15. Conclusion PMMA+10% PEG nanofibers can be used as an effective slow releasing drug delivery system for KynA. Nanofiber-released KynA effectively modulates the expression of ECM components in vitro and in vivo. Application of KynA-loaded nanofibers can improve the wound healing outcome in patients prone to develop skin fibrosis.

16. Dr. Aziz Ghahary Sanam Salimi Dr. Layla Nabai Ryan Hartwell Dr. Reza Jalili Dr. Yunyuan Li Dr. Ruhi Kilani Acknowledgements 16 Collaborators: Dr. Hellen Burt John Jackson Dr. Frank Ko Victor Leung Dr. Emma Guns Dr. Azadeh Taba Dr. Yun Zang Ali Farokhi Dr. Mohsen Khosravi Dr. Saman Pakyari

17. Thank you for your attention!