O 2 gradient in O 2 delivery system
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1 O 2 gradient in O 2 delivery system Huaifa Zhang 1, Jake Barralet 1,2 1 Faculty of Dentistry, McGill University, Montreal, QC, H3A 0C7, Canada; 2 Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, QC, Canada
2 Respiration Air is crucial for our life spiratory.html&h=0&w=0&tbnid=qw1i3bhxqkp7am&zoom=1&tbnh=214&tbnw=235&doci
3 Tissue oxygenation diffused O 2 blood vessel red blood cells O 2 delivery by blood plasma
4 Oxygen is crucial for cell activities Role of O 2 in glucose metabolism in mammalian cells Cell activities require energy, which mainly comes from the oxidative phosphorylation in mitochondria Oxidative phosphorylation can not take place without oxygen Lack of O 2 lack of energy metabolic crisis cell death R. A. Gatenby and R. J. Gillies, Nature Reviews Cancer, 2004, 4,
5 O 2 tension in tissues po 2 Air 21.1% Arterial blood 13.2% Venous blood 5.3% Cell % Kidney 9.4% Liver 5.4% Muscle 3.8% A. Carreau, B. E. Hafny Rahbi, A. Matejuk, C. Grillon and C. Kieda, Journal of cellular and molecular medicine, 2011, 15,
6 O 2 delivery Tissue necrosis Tissue engineering; Wound healing Alleviate hypoxia/anoxia Glycolysis apoptosis angiogenesis Lack of O 2 Preserve tissues; Promote healing Inhibit cell growth
7 Ways to deliver O 2 H 2 O O 2 XO 2 Perfusion bioreactor Perfluorocarbons O 2 -generating scaffold Kasper FK, Riess, J.G. and M. Le Blanc, Pure Appl. Chem, (12): p Harrison, B.S., et al., Biomaterials, (31): p
8 Basic Concept Metal peroxide (CaO 2 ): O 2 generating agent CaO H 2 O = Ca(OH) 2 + H 2 O 2 2H 2 O 2 = 2H 2 O + O 2 Bioplymer capsule: control O 2 release H 2 O H 2 O O 2 Cell CaO 2 Capsule
9 Self-oxygenating scaffold O 2 O 2 -generating agent Alginate hydrogel Artery O 2 -generating agent: CaO 2 -polycaprolactone (PCL)
10 Blood vessel Rat aorta size Diameter (mm) 2.24±0.07 Wall thickness (mm) 0.102± H. WOLINSKY, Circulation Research, 1971, 28,
11 Artery-cold storage Decreasing temperature can reduce metabolic rate by 2-3 times every 10 Cross section Inner layer Cold-7 d Cold+O 2-7 d Green: live Red: dead J. D. Litzgus and W. A. Hopkins, Journal of Thermal Biology, 2003, 28,
12 Artery-normothermic storage Cross section Inner layer 20% O 2-7 d 0% O 2-7 d 0% O 2 +O 2-7 d
13 Artery-normothermic storage Cross section Inner layer 0% O 2 +O 2 (inside)-2 d 0% O 2 +O 2 (outside)-2 d 0% O 2 +O 2 (outside)-7 d
14 Objective The process of O 2 transfer from O 2 -generating agent towards aorta Fick s law J = D c x g g J is the rate of transfer per unit of area ( t cm2); C the concentration of diffusing substance ( cm 3); x the space coordinate measured normal to the section (cm); D the diffusion coefficient ( cm2 ). t
15 O 2 delivery O 2 O 2 -generating agent Artery Alginate hydrogel Decomposition rate of CaO 2 (particle size, available amount of H 2 O, precipitation of Ca(OH) 2 ) Amount of generated O 2 (CaO 2 amount, decomposition rate) O 2 diffusion rate in hydrogel, PCL, medium and artery (diffusion coefficient, O 2 gradient) O 2 consumption (tissue mass, temperature) M. Jamnongwong, K. Loubiere, N. Dietrich and G. Hébrard, Chemical Engineering Journal, 2010, 165, A. Axelsson, B. Persson, Applied biochemistry and biotechnology, 18 (1988)
16 Decomposition rate of CaO 2 CaO 2 CaO 2 -PCL Decomposition ratio (6 h) 41.4% [1] 13.8% [2] [1] CaO 2 powders in 1% alginate hydrogel, 37, culture medium, by XRD data [2] CaO 2 PCL in 1% alginate hydrogel, 37, culture medium, by XRD data J.-S. Yoon, H.-W. Jung, M.-N. Kim, E.-S. Park, Journal of Applied Polymer Science, 77 (2000) P. Das, D. Biswas, S. Roy, International Journal of Drug Delivery, 4 (2012)
17 Diffusion coefficient of H 2 O Hydrogel PCL Diffusion coefficient (cm 2 /s) D = πr 02 (k/4) 1/n [1] [2] Equilibrium H 2 O content in PCL: g/g of PCL [1] D: diffusion coefficient of water (cm 2 min -1 ); R 0 : radius of the dry gel; k: swelling constant; n: diffusional exponent (n = 0.45 indicates Fickian diffusion, 0.5<n<0.89 indicates anomalous transport and n 0.89 implies relaxation-controlled transport). poly-acrylate [2] 36.5, atm H 2 O vapor, Mn 23,200 J.-S. Yoon, H.-W. Jung, M.-N. Kim, E.-S. Park, Journal of Applied Polymer Science, 77 (2000) P. Das, D. Biswas, S. Roy, International Journal of Drug Delivery, 4 (2012)
18 Diffusion coefficient of O 2 Diffusion coefficie nt (cm 2 /s) 1% calcium alginate PCL H 2 O Arteriolar wall Tissues ± [1] C α(hx x2 2U [2] [1] In vivo, mouse [2] C is the external O 2 tension, α is the respiration rate of the tissue, H is the slice thickness in cm and U is the O 2 tension at a point distance x cm inside the surface, a is the solubility of O 2 in the liquid S. K. Young, et al, Polymer, 2002, 43, J. D. B. Macdougall and M. McCabe, Nature, 1967, 215, A.C. Hulst, et al, Biotechnol Tech, 3 (1989) N. Sasaki, et al, The Keio journal of medicine, 61 (2012)
19 O 2 consumption rate O 2 consumption rate (mol min -1 per cell ) Endothelial cells (suspension) 3.07± (mouse, 37 ) 0.61± (pig, 4 ) 1.00± (pig, 22 ) Smooth muscle cells Arteriolar wall (in vivo mouse) 2.64± (pig, 22 ) (mol 100 cm 3 tissue min 1 ) O 2 consumption rate: around mol min -1 per cell R.P. Pandian, V. Kumar Kutala, N.L. Parinandi, J.L. Zweier, P. Kuppusamy, Archives of Biochemistry and Biophysics, 420 (2003) R. Motterlini, H. Kerger, C.J. Green, R.M. Winslow, M. Intaglietta, Depression of endothelial and smooth muscle cell oxygen consumption by endotoxin, 1998.
20 Dr. J.E. Barralet Dr. F. Tamimi Dr. S. Tran Ms. Y.L. Zhang Acknowledgement
21 Artery-cold storage Cross section Inner layer Cold-7 d Cold+O 2-7 d 5 mg/ml particles in 1% gel
22 Artery-normothermic storage Cross section Inner layer 20% O 2-7 d 0% O 2-7 d 0% O 2 +O 2-7 d 80 mg/ml particles in 1% gel; culture medium (DMEM)
23 Example model 2 D system simulation C oxy t = D 2 C oxy + R oxy C oxy : O 2 concentration, R oxy : rate of O 2 production, D: diffusion coefficient of O 2 COMSOL software, Chemical Engineering Reaction module for fine element analysis (COMSOL 2010b; COMSOL 2010a) for CaO 2 decomposition in PDMS (R oxy ) E. Pedraza, M.M. Coronel, C.A. Fraker, C. Ricordi, C.L. Stabler, Proceedings of the National Academy of Sciences, 109 (2012)
24 Solubility of O 2 H 2 O PCL Solubility (ppm) 6.73 ppm (37 ) ppm (25 ) S. K. Young, et al, Polymer, 2002, 43,
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