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Lecture+24-Eng+Native+Matrix - Engineering Engineering...

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Unformatted text preview: Engineering Engineering Native ECM 1. Engineering the stiffness of ECM 2. Engineering ECM distribution 3. Using ECM peptides for surface modification 4. Decellularized ECM 5. Reconstituted ECM 1. ECM Stiffness Engler et al. Cell (2006) Smooth Smooth Muscle Differentiation Stiff Gel B C D No TGF A +TGF F-actin Park et al. (2010) 2. Engineering the ECM Distribution Example--Microprinting: To use the relief pattern on the surface of an elastomeric PDMS stamp to form patterns on the surface of various substrate surface of various substrate. A Effect of Endothelial Cell Spreading Chen et al., Science 276: 1425-8. Effect Effect of Cell Spreading on Cell Growth and Death Effect of Cell Spreading on Actin Cytoskeleton Biomaterials. 2009 Sep;30(25):4203-10. Effect Effect of Cell Spreading on Cell Growth and Death 3. Using ECM peptides (cell binding domains) to modify surfaces Integrins ECM Binding sites 21 collagen, laminin P-15, DGEA 51 fibronectin RGD, PHSRN PHSRN v3 fibronectin, vitronectin, RGD osteopontin Conformation of Collagen and the P-15 domain Strand Bend Strand COLLAGEN TRIPLE HELIX P-15 Proteoglycan receptors bind to specific domains of ECM Example: X-B-B-X-B-X Where B is a basic amino acid: lysine (K), arginine (R), histidine (H) E.g. KRSR for osteoblast adhesion Amino Amino Acid Sequences Useful for Tissue Engineering Fibronectin Collagen Laminin RGDS PHSRN REDV LDV PRARI QGIAGQ DGEA GFOGER GER IKVAV YIGSR RQVFQVAYIIKA GEAALLLELCC YQDPVTLQLA Protein Adsorption • Relatively low yields • Active sites of ligands may be sterically inaccessible • Binding is relatively unstable Surface Surface Bioconjugation • Hydroxyls (C-OH) • Amines (NH) • Carboxylic acids (COOH) • Thiols (SH) • Others: amides, disulfides, phenols, guanidines, thioethers, indoles, imidazoles Activation Coupling X+A X* + Ligand Ligand Example: Surface Bioconjugation on poly(methyl methacrylate) (PMMA) methacrylate) CH3 [ CH2 C ]n PMMA C=O O CH3 Di-amino-PEG CH3 A [ CH2 C ]n C=O OH B CH3 [ CH2 C ]n CH C=O NH CH3 [ CH2 C ]n 1. Sulfo-SMCC 2. CGGGRGDSP PEG NH C=O NH PEG NH2 SMCC CGGGRGDSP Example: Example: Surface Bioconjugation on poly(methyl methacrylate) (PMMA) methacrylate) A C E B D F F Biomaterials. 2006 May;27(14):2890-7 4. Decellularized ECM Skin Biomaterials. 2010 Sep;31(26):6730-7 Decellularized Decellularized Heart Nat Med. 2008 Feb;14(2):213-21 5. Reconstituted ECM Biomaterials. 2009 Oct;30(29):5409-16 ...
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