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Vanessa Aguilar Project Plan October 27, 2010 Natural Materials for Dural Replacement and Neuroprotection.

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Presentation on theme: "Vanessa Aguilar Project Plan October 27, 2010 Natural Materials for Dural Replacement and Neuroprotection."— Presentation transcript:

1 Vanessa Aguilar Project Plan October 27, 2010 Natural Materials for Dural Replacement and Neuroprotection

2 Dural Replacement Therapy Needs Dura lesion complications: Meningitis Cerebral spinal fluid leak Pseudomeningocele Arachnoiditis Epidural abscess Current dural replacement market Gore-Tex (ePTFE) Neuropatch (polyester urethane) Duragen (Collagen) DuraSeal (PEG-based spray) Tisseel (Fibrin/trombin solutions) Preclude (PTFE/ elastomeric fluoiropolymer) History of dural replacement 1895 first dural replacement 1 Mid 90s xenograph and allograph were used Since 70s biosynthetic graft were investigated 14% of spinal surgeries requires a dural replacement technology 2 y/imagepages/17146.htm Matrix.html 1. Stendel et al. J Neurosurg, Cammisa et al, Spine Nasser, R. et al. Covidien _0924jallocase.pdf

3 Anatomical Dural Overview Narotam P. et al, Spine 2004 Stendel R et al.J Neurosurg 2008, Runza et al, Anesth Analg, 1999

4 Dural Replacement / Cranial Adhesion Barriers Barrier DeviceDuraGen (Integra Life Sciences) Synthecel Dura (Synthes) DuraSeal (Covidien) Adherus (HyperBranch) Model DescriptionDuraGen/DuraGen Plus® is an innovative matrix designed to prevent peridural fibrosis and adhesions Cellulose – microbially grown cellulose PEG hydrogelSynthetic surgical sealant – PEG hydrogel blend Properties Collagen based Added cellulose layer for suturable performance Thick, very strong sheets of cellulose 100% synthetic Water-tight sealant to be applied during cranial or spinal surgeries for dura repair CE approved for spinal applications Advantages FDA approved for neural applications Natural-based material Bioresorbable but degradation resistant FDA approved for dural replacement and wound dressing Phase III clinical trials FDA approved for cranial and spinal surgeries. Injectable and easy to use Spray-use, easy to use Disadvantages Not easy to handle Not an adhesion barrier Attracts adhesions Very expensive Timely to grow Cannot be grown mass-scale Set up required Synthetic Can be procoagulant Nerve compression may ocur 1 Set up required Synthetic Can be procoagulant 1. Spotnitz, W and Burks, S. Transfusion. 2008

5 Plan of Work GOAL: To develop composite, dual-functioning materials that would serve to encourage healthy cell growth, wound healing and inhibits post-surgical scar tissue formation for neural applications. We aim to develop an all-in-one product to replace dural tissue as well as support healthy healing. AIM 1: Develop and characterize suturable anti-adhesion film / foam Biocompatible Non-immunogenic Non cell-adhesive / cytotoxic Inhibits protein absorption Mechanically robust Watertight / sealing Anti-fibrotic AIM 3: Drug release studies Biocompatible Effective at reducing adhesions Encapsulate aspirin or ibuprofen Tunable release rates AIM 2: Develop bilayer biofunctionalized HA- based film Biocompatible Bioabsorbable Non-immunogenic Dual functioning Regenerative Anti-adhesive Mechanically robust Cost effective Clinically sized Repositionable

6 GOAL: To develop composite, dual-functioning materials that would serve to encourage healthy cell growth, wound healing and inhibits post-surgical scarred tissue formation for neural applications. We aim to develop an all-in-one product to replace dural tissue as well as support healty healling. AIM 1: Develop and characterize suturable anti-adhesion film / foam Biocompatible Non-immunogenic Non cell-adhesive / cytotoxic Inhibits protein absorption Mechanically robust Watertight / sealing Anti-fibrotic AIM 3: Drug release studies Biocompatible Effective at reducing adhesions Encapsulate aspirin or ibuprofen Tunable release rates AIM 2: Develop bilayer biofunctionalized HA- based film Biocompatible Bioabsorbable Non-immunogenic Dual functioning Regenerative Anti-adhesive Mechanically robust Cost effective Clinically sized Repositionable Plan of Work

7 Material Properties Biocompatible Bioabsorbable / non-immunogenic (non- animal) Very non-cell adhesive, polyanionic, hydrophilic Antifibrotic 1 (1% HMW HA) Pro-angiogenic Shown to reduce adhesion formation in animals and humans 2 Clinically used to reduce adhesions: Seprafilm, most effective and widely used anti-adhesion barrier on the market Alginate Hyaluronic Acid 1. Massie et al, The Spine Journal, Zawaneh et al, Tissue Eng Part B Dusseault et al. Wiley InterScience, 2005 Jeon et al, Biomaterials, 2009 Biocompatible Low toxicity Gels at physiological pH and temperature Very non-cell adhesive, polyanionic, hydrophilic Poorly immunogenic (depends on alginate purification) 3

8 Anti Cell-Adhesion Properties 2. Culture fibroblast cells hours in culture 4. Fix and stain for DAPI. 5. Validate cell-adhesion / non cell- adhesions 1. Well and film

9 Results Alginate Alginate /GMHA Alginate /GMHA /HA Control There is significant difference between control and films (p < 0.005)

10 Cytotoxicity 1. Culture fibroblast cells 2. Seed cells in PLL coated TC coverslips 4. Stain coverslips with calcein / ethidium to label live / dead cells. 5. Evaluate cytotoxicity 4. Wait 24 hours 5. Place Alginate / HA film supernatant on top of cells 3. Place Alginate / HA film on cell medium 4. Wait 24 hours

11 Results AlginateAlginate /GMHA Control There is no statistical difference between control and films in live and dead assay

12 Antifibrotic studies (using laminectomy model) 1. Collect the tissue 2. Dehydrate in ethanol 3. Acid decalcify 4. Wait for 3 days 5. Slice every 50 um 6. Stain with H./E and Massons trichrome staining and analyze

13 Watertight Studies K. Hida et al. Surgical Neurology 65 (2006) 136–143 Manometer

14 Protein Adsorption Studies 2. Rinse with PBS Huang and Yang, Polymers advanced technologies, 2009 Film 1. Shake for 24 hours at 37 ˚C Human serum albumen and human plasma fibronectin 3. Addition of sodium dodecyl sulfate (SDS) 5. Measure absorbance at 562 nm with UV/Vis spectrometer 4. Stain with BCA protein assay reagent 6. Measure and analyze samples

15 Acknowledgments PI: Dr. Christine Schmidt, Graduate Students: Sarah Mayes

16 Current Technologies Autologous grafts Pericranium or temporal fascia Xenografts and allografts Menengitis and Creutzfeldt-Jacobs Disease Natural and syntethic materials Gore-Tex (ePTFE) Neuropatch (polyester urethane) Duragen (Collagen) DuraSeal (PEG-based spray) Tisseel (Fibrin/trombin solutions) Preclude ( PTFE/ elastomeric fluoiropolymer) Matrix.html Stendel R et al. 2008, J Neurosurg 209:

17 Results AlginateAlginate /GMHA Alginate /GMHA/HA Control There is no statistical difference between control and films in live and dead


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