1. Founder and Chief Scientific Officer
Enabling the Next Generation of Drug Delivery Through Implantable Medical Devices
Kevin D. Nelson, Ph.D.
Founder and Chief Scientific Officer
TissueGen, Inc.

2. Disclosure Statement
Dr. Nelson serves as Founder and Chief Scientific Officer for TissueGen, Inc. which has developed and markets products related to the research described in this presentation.

3. Overview Drug Delivery from Medical Fiber
Tissue Engineering Applications

4. Drug Delivery from Medical Fiber Advantages of Fiber
Slower Release than Microspheres
Mechanical and Pharmaceutical Support
Localized (Non-systemic) Drug Delivery

5. Drug Delivery from Medical Fiber Manufacturing Methods
Melt Extrusion
High temperature (typically > 200 degrees C)
High shear stress
Wet Extrusion
Low temperature (typically at or below body temp)
Low shear stress
Harmful solvent exposure
Residual solvent removal

6. Drug Delivery from Medical Fiber Polymers
Poly(L-lactic co-glycolic acid) [PLGA]
Poly(ԑ-caprolactone) [PCL]
Poly(L-lactic acid) [PLLA]
Poly(p-dioxanone) [PDO]
Proprietary Blends
Natural Polymers

7. Drug Delivery from Medical Fiber Fiber Formats
Circular
Ribbon
Hollow
Gel-filled
Multi-lumen
Over-the-wire

8. Drug Delivery from Medical Fiber Medical Device Formats
Coils
Stents
Sutures
Medical Textiles

9. Drug Delivery from Medical Fiber Pharmaceuticals
hydrophilic
hydrophobic

10. Drug Delivery from Medical Fiber Biologics
Growth Factors
Other Proteins
Viral Particles

11. Drug Delivery from Medical Fiber Protection of Sensitive Proteins
BDNF half life 22 hours in buffer system.
Over 100 days release possible with protein protection within fiber.

12. Drug Delivery from Medical Fiber Controlled Sustained Release Profiles

13. Drug Delivery from Medical Fiber Tailored Release Profiles

14. Drug Delivery from Medical Fiber Drug Delivery and Tissue Engineering

15. Tissue Engineering Applications Nerve Growth Factor PC-12 Cell Assay
PC-12 cells sprout neurites in presence of biologically active NGF
NGF loaded fiber in culture with PC-12 cells
Panel A: No NGF
Panel B: 5 cm NGF fiber
Panel C: 10 cm NGF fiber A B C

16. Tissue Engineering Applications Nerve Growth Factor Dose Response
Neurite process length proportional to amount of biologically active NGF.
Dose Response: 10cm fiber dosage nearly twice activity of 5cm fiber.

17. Tissue Engineering Applications Peripheral Nerve Regeneration
Rat Sciatic Nerve
Fiber Scaffold

18. Tissue Engineering Applications Axon Guidance Non-Drug Loaded Fibers

19. Tissue Engineering Applications Tissue Guidance by Concentration Gradient

20. Tissue Engineering Applications Aldose Reductase Inhibitor Release

21. Tissue Engineering Applications Diabetic Retinopathy

22. Tissue Engineering Applications Adenovirus Release from Gel-Bored Fiber

23. Tissue Engineering Applications Nicotine Release Promoting Angiogenesis in Mouse

24. Summary Drug Delivery from Medical Fiber
Tissue Engineering Applications

25. Additional Information
Kevin D. Nelson, Ph.D.
TissueGen, Inc.