1. Richelle C. Thomas, Christine E. Schmidt University of Texas at Austin

2.  Over 20 million Americans suffer from some form of peripheral neuropathy The Neuropathy Association

4.  Global Prevalence  60-70% of diabetics have mild to severe nervous system damage  Diabetic foot ~80% of non- traumatic amputations  Largest diabetic population: ▪ India, China, US  Largest cause of PN in west  US Prevalence  10.7% US aged 20 & older  23.1% US aged 60 &older  Cost  US $174 B in 2007 National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics, 2007 fact sheet. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, 2008.

5.  Easy to injure  Trauma  1.5-2.8% incidence rate  War  35% troops extremities wounded in combat Journal of Craniofacial Surgery. 21(4):998-1001, July 2010.

6. End-to-End Suturing Bridging Grafting Conduit/Implant Ciardelli G, Chiono V. 2006. Materials for Peripheral Nerve Regeneration. Macromol. Biosci. 6:13-26 Communication between nerve stumps Physical guidance to regenerating axons

7. Chemical Contact Electrical Lee et al. (2002) Gomez et al. (2006) Huang et al. (2008) For more information on stimuli integration see Forciniti et al. ABME. (2008).

8.  Soft tissue scaffold  Focus on injury  Supports wound healing  Reduces inflammation  Promotes tissue reorganization

9. Hudson TW, Evans GR, Schmidt CE. 1999. Engineering strategies for peripheral nerve repair. Clin. Plast. Surg. 26:617–28

10. Artif Organs V 30 No 7 2006 Degradation rate Comparable to new tissue formation Biocompatible Inflammatory Response Mechanically sound Not collapse Biodegradability Room for tissue growth No need for 2 nd surgery

11. Artif Organs V 30 No 7 2006 Degradation rate Comparable to new tissue formation Biocompatible Inflammatory Response Mechanically sound Not collapse Biodegradability Room for tissue growth No need for 2 nd surgery Naturally Derived Polymer Hydrogels PBS Swollen    

12.  Extracellular matrix component  Polyanionic  Hydrophillic  Involved in mediating wound repair  Non-cell adhesive

13. Modulate Swelling Degradation Mechanical Properties Advantages Biocompatible Non-cell adhesive Control local chemical properties Optically transparent High Swelling HA Hydrogels 1 min 20 min2 min 5 min10 min UV Exposure

14. Problem: Amorphous gels only offer chemical and no physical cues

15. Hyaluronic Acid gels beneficial for wound healing applications Problem: Hydrogels are amorphous and do not provide any significant physical contact guidance to infiltrating cells beyond their inherent porosity

16. Physical cues are preferred over chemical cues for axon initiation (polarization) 70 %  Physical Cues (microchannels) 30 %  Chemical Cues (NGF or Laminin) Microchannels vs. Laminin 25  m 12  m Gomez, Chen, Schmidt (2007). J. R. Soc Interface. 4(13): 223-233. Gomez, N., Schmidt, C.E. (2007) Biomaterials. 28 (2): 271-284

17. Neurons extended longer and more oriented axons on surfaces with combinatorial cues. Gomez, N., Schmidt, C.E. (2007) Biomaterials. 28 (2): 271-284 Hippocampal cells on PDMS Microchannels w/immobilized NGF (0.11 ng/mm 2 ) Scale bars=10 μm

18. Hyaluronic Acid gels beneficial for wound healing applications Problem: Hydrogels are amorphous and do not provide any significant physical contact guidance to infiltrating cells beyond their inherent porosity

19. Develop natural polymer hydrogels that have 3D internal architecture Extend internally patterned films into 3D hydrogel constructs

20. 32% Methacrylated Hyaluronic Acid 50 mg/ml GMHA 0.1-1% Photoinitiator

21. High Swelling HA Hydrogels 1 min 20 min Modulate Swelling Degradation Mechanical Properties Advantages Biocompatible Non-cell adhesive Control local chemical properties Optically transparent 2 min 5 min10 min UV Exposure

25. connectivity among the pores of the scaffold protein diffusion was restricted to the pores tightly crosslinked, low-permeability hydrogel Scale bar: 10 lm. Zawko, S.A., et al. (2010. “Crystal templating dendritic pore networks and fibrillar microstructure into hydrogels.” Acta Biomaterialia 6(7): 2415-2421 TRITC- labeledGreen fluorescent albumin–FITC

26.  Degradation rate, swelling dependent on UV exposure & PI concentration  Storage moduli consistent over frequency range  Tunability of mechanical properties makes system for variety of applications  Drug delivery  Vascularization

27.  Peripheral Nerve Regeneration  Determine swollen pore size of 3D hydrogels with confocal microscopy  Render porous network cell-adhesive and evaluate cell mobility within hydrogel.  Other applications  Incorporate anti-inflammatory agents into hydrogel matrix to evaluate ability to provide sustained drug release over time

28.  Dr. Christine E. Schmidt  Labmates  Leandro Forciniti, Sarah Mayes, John Hardy  Undergraduate Researchers  Shan Modi, Paul Chung