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MIT 3 052 - INTRODUCTION TO BIOADHESION

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Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33INTRODUCTION TO BIOADHESIONCHRISTINE ORTIZ, Associate ProfessorDepartment of Materials Science and Engineering, MITWWW : http://web.mit.edu/cortiz/wwwcD. Breger, used w/permission, http://www.ldeo.columbia.edu/micro/images.section/pages/bloodclot.htmlBIOADHESION : DEFINITIONBioadhesion may be defined as the state in which two materials, at least one of which is biological in nature, are held together for extended periods of time by interfacial forces. In the context of their medical and pharmaceutical use, the term bioadhesion refers to the adhesion of synthetic and biological macromolecules to a biological tissue. The biological substrate may be cells, bone, dentine, or the mucus coating the surface of a tissue. If adhesive attachment is to a mucus coating, the phenomenon is sometimes referred to as mucoadhesion.Many examples of bioadhesion exist in nature, including such diverse events as cell-to-cell adhesion within a living tissue, barnacles binding to rocks, and bacteria binding to tooth enamel. In health care, bioadhesives were first used as wound dressings, skin adhesives, and denture fixatives. Over the last two decades, bioadhesives have been of interest within the pharmaceutical sciences for their potential to optimize drug delivery. Such drug delivery may be optimized at the site of action (e.g., on the cornea or within the oral cavity) or at the absorption site (e.g., in the small intestine or nasal cavity). Bioadhesives may also be used as therapeutic agents in their own right, to coat and protect damaged tissues (gastric ulcers or lesions of the oral mucosa) or to act as lubricating agents (in the oral cavity, eye, and vagina). Skin adhesives, tissue sealants, and dental and bone adhesives and cements are also defined as bioadhesives.This article first focuses on the types of muco/bioadhesives currently used in the pharmaceutical sciences, from first-generation hydrophilic polymers to second-generation polymers and lectins. The nature of bioadhesive interactions, types of bioadhesive formulations developed, and regions of the human body to which they may be administered are also considered.Other types of medical bioadhesives, such as those used in wound management, surgery, and dentistry, are also discussed.Blood and Blood Vessels40% cells in plasma or serum (pH7.4, IS=0.15 M) which contains 6-8% proteins (over 3,000 different types) in HOH, including :-58% albumins-38% globulins-4% fibrinogenshttp://www.artegraft.com/Synthetic Vascular Grafts or Prosthesis : prosthetic tube that acts either a permanent or resorbable artificial replacement for a segment of a damaged blood vessel (e.g. from athersclerosis,aneurysms, organ transplant, cancer, arteriovenous fistula, diabetes) : $200 million market worldwidehttp://www.atriummedical.com/http://www.vascutek.com/• expanded polytetrafluoroethylene(Gore-Tex, ePTFE)-fibrillated, open cell, microporous (pore size 0.5-30 m), 70% air, nonbiodegradable, chemically stable, used for 26 yrs, hydrophobic/nonpolar, flexible• polyethylene terephthalate(Dacron, PET)-multifilamentous yarn fabricated by weaving/knitting, amphiphilic, smaller pores than ePTFE• polyurethane derivatives• bovine collagen-fibrous, hydrophilicZhang, et al. J. Biomed. Mtls. Res.60(3), 2002, 502.Vascular Graft MaterialsOOOOnFF FFnwww.vascutek.comadsorbs BLOOD PRESSURE+ATTRACTIVE FORCESdenaturesPLATELETS!http://www.rinshoken.or.jp/org/CR/photo-e.htmSolid-Liquid Interfaceblood plasma proteinsBLOOD FLOWBIOMATERIAL SURFACEBLOOD CLOT!-acute occlusive thrombosis- infection / inflammation- neointimal hyperplasiaD. Gregory http://medphoto.wellcome.ac.ukTotal Intersurface Force as a Function of Separation Distance :F(D)WHAT CONTROLS PROTEIN ADSORPTION?END-GRAFTED POLYMER “BRUSHES”ADSORBED POLYMER LAYERS BIOMATERIAL SURFACEMany different components, both attractive (e.g. hydrogen, ionic, van der Waals, hydrophobic, electrostatic) and repulsive (e.g. configurational entropy, excluded volume, osmotic, enthalpic, electrostatic, hydration), can lead to complex interaction profiles.Dchemically end-grafted PEO50K “mushroom”Lcontour= 393 nmRF=8.7 nmFsodium phosphate buffer solutionIS=0.01M pH=7.4Dlipid-bound HSA functionalized probe tip, RTIP~65 nm (SEM)Au-coated silicon chipcovalently immobilized HSA~10 nms = 62 ± 28 nm~35-190proteins in maximum interaction area (D=0)~2.5 PEO chains in maximum interaction area (D=0)Si3N4Direct Measurement of Protein Interactions with Poly(ethylene oxide) (PEO) MacromoleculesRixman, et al. accepted, Langmuir 2003.Chemical Attachment Scheme of Lipid-Bound HSA to Si3N4 Probe TipA. Vinkier; Heyvaert, I.; D'Hoore, A.; McKittrick, T.; C., V. H.; Engelborghs, Y.; Hellemans, I. Ultramicroscopy 1995, 57, 337. S. O. Vansteenkiste; Corneillie, S. I.; Schacht, E. H.; Chen, X.; Davies, M. C.; Moens, M.; Van Vaeck, L. Langmuir 2000, 16, 3330.HSAHSASi OHIIOONH2NH2H2NIIIH3C O SiCH3CH3NH2ABDMSSiNH2Si NH2Si O Si NH2CH3CH3NH2NH2Glutaraldehyde+Si3N4 Probe TipNSi NH2SiNH2Si O SiNCH3CH3SiNSiNSi O SiNCH3CH3OOOOOSiNOOSiNOOIFluorescence micrographof HSA-functionalizedcantilever (courtesy of Irvine Lab-DMSE)probe tiplocation(*Steve Santoso (MIT-Biology) http://pymol.sourceforge.net) Human Serum Albumin (HSA)M. O. Dayhoff Atlas of Protein Sequence and Structure; National Biomedical Foundation: Washington DC, 1972.S. Azegami; Tsuboi, A.; Izumi, T.; Hirata, M.; Dubin, P. L.; Wang, B.; E., K. Langmuir 1999, 15, 940-947.IIThe smallest and most abundant blood protein in the human body, HSA accounts for 55% of the total protein content in blood plasma3-D structure consists of 3 homologous subdomains, each containing 5 principal domains and 6 helices.Subdomains form hydrophobic channels placing basic and hydrophobic residues at the ends while the surface remains predominantly hydrophilicLcontour = 225 nmIsoelectric point=4.7116 total acidic groups (98 carboxyl and 18 phenolic -OH) and 100 total basic groups (60 amino, 16 imidazolyl, 24 guanidyl).I(N)IIIII(C)“HEART SHAPED” STRUCTURE OF CRYSTALLIZED HSA(Curry, S., H. Mandelkow, et al. Brookhaven Protein Databank.)C8 nmPROPOSED ELLIPSOIDAL STRUCTURE OF HSA IN SOLUTION(Haynes, et al. (1994). Coll. Surf. B. : Biointerfaces 2:


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MIT 3 052 - INTRODUCTION TO BIOADHESION

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