Slides for class.pdf
- 2. Minor 1 Overview Polymers & fibres Design criteria & fabrication methods Classification of Med Textile field Non-implantable materials: Wound dressing, Bandages, Gauges Implantable biomaterial textiles: Vascular grafts, Sutures, Heart valves Minor 2 Hernia mesh Scaffolds for Tissue Engineering : Cartilage (nonwoven, 3D weaving) , Skin (nonwoven, weaving) , Liver (rapid prototyping) , Kidney, Urinary bladder (nonwoven, 3D weaving) , Tendons, Ligaments (Silk filaments, braiding), Cornea Major Healthcare & hygiene products: Surgical Gown, mask, wipes, Antibacterial Textile, Super absorbent polymer, Dialysis, adhesive, anti- adhesive patches for Surgical application, Coating & finishing technologies Characterizing tests, Evaluation of commercial Med Textiles products, Standards….. Legal & ethical issues
- 3. Term Paper : students should identify existing specific clinical problems, & propose novel solutions using ‘smart’ Medical Textiles. (2 students per group) Course structure Minor 1: 25% Minor 2: 25% (Open book) Major: 35- 40% Quiz, Term report: 10-15%
- 4. use or close imitation of the language and thoughts of another author and the representation of them as one's own original work the wrongful appropriation or purloining and publication as one's own, of the ideas, or the expression of the ideas… of another Identification of problem & innovative approach: 40% Originality of write up: 55% Presentation of selected proposals: 5% 1-2 proposals will be forwarded for patent filing
- 5. • Papers to be distributed in class • Medical Textiles, by Subhash Anand, Woodhead Publishing Ltd • Medical Textiles and Biomaterials for Healthcare, Ed by S.C. Anand, M Miraftab, JF Kennedy, Woodhead Publishing Ltd, 2005 • Medical Textile monthly newsletters, Technical Textiles Net Publications • Medical Textiles 2007: Proceedings of 4th Int conf on healthcare and medical textiles, By JF Kennedy, SC Anand, M Miraftab, S Rajendran, CRC Press • Principles of Tissue Engineering, by Lanza, Langer, Vacanti • Tissue Engineering Journal, Mary Ann Liebert Inc. Publications
- 6. Time Magazine online, http://www.time.com/time/magazine/article/0,9171,997028,00.html Hottest future professions of the twenty-first century May, 2000
- 7. Higher expectations of quality of life Textile products that have been engineered to meet specific needs of suitable medical & surgical applications, related to hygiene & healthcare Rising standards of living Changing attitude 2004: number of people aged over 60 amounts to 40% of the entire population. 2009: 66.57 years 2010: 83 years (Japan)
- 8. Market Size & Potential (Rs. Crore) Market Size & Potential (Rs. Crore) S. No Technical Textile Sector 2003-04 2007-08 2005-06 (Actual) Assumed growth rate per annum (%) 2014-15 (Predicted) 1 Clothtech 6833 8415 7583 15 26677 2 Packtech 4602 7359 5152 12 14288 3 Indutech 2212 2993 1148 12 3182 4 Sporttech 1534 2049 1773 15 6238 5 Meditech 1525 2339 1152 20 % 5945 6 Mobiltech 1323 2046 1532 10 3613 7 Hometech 1029 1897 1398 15 4918 8 Agrotech 303 464 376 20 1938 9 Protech 284 638 819 10 1931 10 Buildtech 281 478 1333 20 6877 11 Oekotech 200 6732 42 10 98 12 Geotextiles - 6591 999 10 2357 TOTAL 20128 42006 23307 14.37 78060 Market size of Technical textiles in India Tata Economic Consultancy Services road map for Indian Technical Textile sector
- 9. ‗Technical Textiles and Industrial Nonwovens: World Market Forecast to 2010‘ published by David Rigby Associates ACS: Globally, the market for biomaterials is expected to reach $88 billion within the next three years, growing at a rate of 15 percent from 2012 to 2017. All of the major United States funding agencies have programs to support work on this topic and related research areas, totaling nearly $1 billion. Two European Commission programs have allocated about $15.6 billion for biomaterials research between 2013 and 2017.
- 10. Current Indian scenario Sanitary napkins, baby & adult diapers : 35% Surgical wound dressing : 30% Sutures : 20% Medical devices & other healthcare textiles: 15% (angioplasty, bypass surgery, stent, compression garments, masks) Tissue regeneration
- 11. Use of Textile-based constructs for Med Textile & Tissue eng Major challenges ahead: 1. Innovative designing 2. Better understanding of structure-function relationship 3. Multidisciplinary approach of problem solving 4. GMP for Biological testing – in vitro, in vivo studies 5. Ethical regulations & Funding Safe but cheaper solutions
- 13. What Constitutes Medical Textiles ? Polymers (& Liq crystals, hydrogels)– Biocompatible Chemicals – Medical Products Fibres & Yarns - Normal, Functional Fabrics – Woven, Non-woven, Knitted, Braided Fabrication Techniques – Molding, Casting Products and Technologies Chemistry, Fibre Technol, Textile Engineering, Mechanical Eng, Chemical Eng, Computer Sci, Product development, Biology, Biotechnology, Instrumentation & Biomed Eng
- 14. Healthcare products Medical Textiles Non- Implantable materials Implantable materials Scaffolds for Tissue engineering Suture Hernia mesh Vascular graft Gown Mask Incontinence Sensors
- 17. Knitted heart valve developed at IITD Commercially available valve
- 19. • What matrix should be used? – Material of fabrication (metal/ ceramic/textile ?) – How to be manufactured? pore characteristics, absorbability, mechanical properties? • What cells are to be used? – Source of cells? – Under what conditions can cells be expanded in vitro while retaining their phenotype? • What regulators are required to stimulate cell ? – proliferation & matrix synthesis or to facilitate differentiation of stem cells? • Instrumentation
- 20. Biocompatible Polymers Ease of processing - versatility of options Improve strength - orientation, fibre-hydrogel composites, crosslinks Bio-inert ……………. degradable FDA Approved synthetic biodegradable polymers ( ― for specific applications ‖ ) PLA, PGA, PLGA, Poly(caprolactone), Polydioxanone Biodegradable polymers derived from natural sources modified polysaccharides (cellulose, chitin, dextran, alginate) Silk, modified proteins (fibrin, casein)
- 21. Collagens & Elastins: the proteins of connective tissues. tendons and ligaments. Keratins: proteins that are major components of skin, hair, feathers and horn. Fibrin: a protein formed when blood clots. De Humnai Corporis Fabrica Libri (On the Fabric of the Human Body) Andreas Vesalius (1514–1564) 1543 Basel, Switzerland Collagen fibre Nerve fibres Elastic fibres Muscle fibres
- 23. The major ECM molecules present in tissues 1. Collagen fibres. 2. Elastin fibres. 3. Proteoglycans and glycosaminoglycans (GAGs). 4. Cell-adhesion molecules (fibronectin, laminin, etc). 5. Water (about 65%). Fibrous proteins are insoluble in water, due to a high percentage of hydrophobic amino acids in their primary structures
- 24. 30% of the human proteins consist of collagen Collagen is the basic building material of fibrous connective tissue of living organisms. Parallely oriented collagen fibres Randomly oriented collagen fibres on skin Uniaxial orientation in tendon, biaxial orientation in dermis Bone Blood vessels Orientation of collagen fibres determines the mechanical behavior of the tissue.
- 25. Characteristics of collagen fibres: digitation on surface Stem cells producing small collagen fibre fragments Collagen molecules produced by the cells self-assemble into fibres. These fibres provide functional integrity of tissues. 35% Glycine 11% Alanine 21% modified hydroxyproline and proline
- 26. Primary structure: complete sequence of amino acids in the polypeptide chain. Scale: 1 nm. Secondary structure: local spatial arrangement of backbone atoms single peptide stands that are wound in a left handed helix. Scale: 10 nm Tertiary structure: 3D arrangement of entire polypeptide chain including side chain Three helical polypeptide units twist to form a triple-helical collagen molecule: a molecular ―rope‖ which has some bending stiffness and does not undergo rotation. Quaternary structure: Association of 2 or more subunits in 3D space Several collagen molecules pack side-by-side in a highly specific register to give a crystalline fiber with a 64-67 nm periodicity (collagen banding pattern).
- 27. Collagen fibres form complicated structures of inner and outer membranes of the organs. 19 different amino acids…… 6 types of collagen fibres. Collagen I : striated fibres…….. Blood vessel wall, tendons, ligaments, bone 80-160 nm in dia high tensile str ( Young‘ s mod 1 X 109 Pa ) Collagen II : < 80 nm dia…… cartilage, intervertebral disc Collagen IV : abundant in Basement membrane Collagen VI : joins cells with surrounding matrix
- 28. three polypeptide chains assembled into a rigid triple helix The strength of collagen macromolecule comes from the hydrogen bonds between the α-chains
- 29. Metalloprotein enzyme Collagenase degrades collagen fibers. Melting of collagen to gelatin (loss of tertiary structure) spontaneously follows such degradation.
- 30. Elastin fibres fibrous protein acts to impart elasticity and resilience to tissue Present in walls of large arteries, ligaments, lungs, skin A network of randomly coiled macromolecules. (GVGVP)n No periodicity. Highly extensible chains.
- 31. It is more compliant than collagen Young‘s mod 3 X 109 Pa Tropoelastin (72 kDa soluble precursor protein of elastin) has potential to self-assemble. Highly insoluble due to interchain crosslinks half-life of 70 years.
- 33. elastin-like peptides ((Val-Pro-Gly-Val-Gly)n, (Gly-Val-Gly-Val-Pro)251, (Gly-Val-Gly-Ile-Pro)260 etc) recombinant elastin (expressed in a bacterial system) Spontaneous retraction of stretched elastin Stretching of elastin fibers leads to large entropy loss due to reduction in chain configurations & increased ―ordering‖ of water molecules against nonpolar amino acids. Degradation Elastase proteinases (aspartic, cysteine, serine, and metallo)
- 34. Silk Silica hydroxyapatite PEO DIAMETER <100 mm microns CHEMICAL DECORATION - cell functions - MINERALIZATION – composites - CRYSTALLINITY b-sheets MORPHOLOGY – surface area Processing Options for Protein Biomaterials Processing Options Protein-Based Biomaterials – silk BMP2 RGD Courtesy: Prof D Kaplan, Tufts
- 35. (i) Biocompatibility: Silk sutures (FDA approved), cyto-compatible, less immunogenic and inflammatory than collagens or polyesters such as PLGA (ii) Stability and Mechanical Properties: remarkable strength & toughness, tensile/compressive strength and modulus…… exceed other commonly used degradable polymeric biomaterials. thermal stability - can be autoclaved without loss of mechanical integrity stabilized by beta sheet secondary structures which are physical crosslinks formed via hydrogen bonding and hydrophobic interactions via inter- and intra-chain interactions. (iii) Modifiable: chemical decoration with RGD peptide, BMP2 and other cell modulating factors using facile carbodiimide coupling attachment of antimicrobial peptides. (iv) Slow Degradability: fast (weeks) to very slow (years) Why Silk is suitable for Medical applications ?
- 36. Nephila clavipes (spider silk) Bombyx mori silkworm
- 37. random-coil silk I alpha-helical conformations 5-10% silk II beta-sheet
- 39. Process of silk film production and culture system preparation Silk cocoons Boiling- NaCO3 solution Rinse Fibroin extract and dry overnight Dissolve fibroin extract in 9.3 M LiBr Dialyze LiBr out of Fibroin soln. for 48 hrs. Cast fibroin soln. upon molding surface Dry fibroin film and air lift from cast surface
- 41. Alginate Seaweed – brown algae Azotobacter vinelandii, Pseudomonas Fibre properies depend on ratio of G and M High G content brittle gel α (1-4) High M content elastic gel β (1-4)
- 42. Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Egg box model Ca2+
- 43. Preparation of Alginate fibre for wound care Wet spinning of alginate fibres containing 25% w/w branan ferulate 1% w/v concentration of calcium chloride. ( Miraftab M, Qiao Q, Kennedy JF, Groocock MR, Anand SC, Advanced wound care materials: developing an alginate fibre containing branan ferulate. J Wound Care. 2002;11(9):353-6 ) Seaweed + 0.1- 0.2 N mineral acid Neutralization with NaOH Precipitation in CaCl2 Parameters: NaCl/CaCl2 ratio, Exposure time, Concentration & mol weight of modifiers Method of isolation
- 44. Cospinning of Alginate with other polysaccharides (such as chondroitin sulphate, dermatan sulphate, heparan sulphate or heparin) (Qin Y, Gilding DK, Advanced Medical Solutions Limited (GB) , Fibres of cospun alginates, United States Patent 6,080,420 , June 27, 2000 ) Degradation Lyases (bacteria, fungi) specifically depolymerise alginate hydrolysis of the glycosidic bonds
- 45. Chitosan poly β(14)-2-amino-2-deoxy-D-glucopyranose Extent of deacetylation governed by alkali conc and time of reaction. Degree of deacetylation & MW influence characteristics of chitosan non-toxic, non-allergenic, anti-microbial, and biodegradable Chitin, poly β(14)-2-acetoamido-2-deoxy- D-glucopyranose Deacetylation of chitin by alkali generates chitosan crustacean, insects, fungi, yeasts
- 46. Fibers kept in this coagulation medium for 1 day & washed with distilled water. Fibres are suspended in aq. 30% methanol for 4–5 hr & in 50% methanol overnight. chitosan dissolved in aq. 1-2% (v/v) acetic acid by stirring at room temp overnight. Plasticizer (e.g., PEG, Glycerol) at 1-2% (w/w) concentration added (optional) filtered and injected into a coagulation bath at 40oC containing a mixture of 30% 0.5 M Na2SO4, 10% 1M NaOH and 60% distilled water. Method of isolation Waste crab shell Dil NaOH Deproteinization Demineralization Dil acid Decoloration Chitin Chitosan Method of Chitosan fibre preparation Hudson SM, Review of Chitin and Chitosan as fibre and film formers, J Mater Sci, Mater Med, C34(3) 375-437, 1994
- 47. ‗‗Intelligent‘‘ or ‗‗smart‘‘ materials Smart Hydrogels are water-swollen polymeric networks containing chemical or physical crosslinks, which can undergo volume transitions in response to minute changes in environmental stimuli such as pH , ionic strength , temperature or electric fields etc. pH sensitive-ness of Chitosan Insoluble Soluble Alginate Ca2+, <pH 2 EDTA, > pH 2 Chitosan > pH 6.5 < pH 6.5 increased intermolecular electric repulsion
- 48. —NH3+ groups of glucosamine negatively‐charged cell membrane of many fungi, bacteria membrane integrity and permeability are affected, leakage of intracellular substances, and finally cell death positively‐charged chitosan with DNA of fungi and bacteria, inhibiting RNA and protein synthesis Chitosan loses antimicrobial activity at pH 7
- 49. Chitosan‐based wound dressings: HemCon® Bandage and ChitoFlex wound dressings (HemCon Medical Technologies Inc., UK), CELOXTM (Medtrade Products Ltd., England) Degradation breakable glycosidic bonds. Chitin and chitosan can be degraded by Lysozyme, Papain - which acts slowly to depolymerise the polysaccharide…. Chitosanase Chitosan is known to degrade in human serum in vitro. eight human chitinases have been identified The biodegradation rate of the polymer is determined by the amount of residual acetyl content.
- 50. Hyaluronic acid Fidia Advanced Biopolymers, Italy Hyaff-11: an esterified form of hyaluronan. Partial esterification of carboxyl groups reduces water solubility, increase viscosity. The esterification process results in a highly hydrophobic polymer that can be spun, or woven. alternating b-1,4 and b-1,3 glycosidic bonds rooster combs umbilical cord bovine vitreous humor
- 51. Hyaff-11 : degradation time of around 40-45 days During in vivo degradation Hyaff-11 fibres become more and more hydrophilic, forming a gel similar to native hyaluronan found in the extracellular matrix. Hyaluronidase Degradation
- 52. Degradable polyesters (- O –CH2 –C -)n =O (- O –CH –C -)n =O CH3 PGA PLA Control copolymer features via synthesis conditions Poly(lactic-co-glycolide) (PLGA) relatively hydrophobic hydrolytic cleavage of the ester bonds, the rate is slower than PGA
- 53. Polylactic acid 1932: Carothers condensation polymerisation of lactic acid 1966: Polylactic acid based biodegradable surgical implants Kulkarni RK et al, Polylactic acid for surgical implants. Arch Surg. 1966; 93(5):839-843 1967 : Absorbable suture : Davis & Geck (Dexon TM) Leenslag JW et al. Resorbable materials of poly(l-lactide) V Influence of secondary structure on the mechanical properties and hydrolysability of poly(l-lactide) fibres produced by a dry spinning method. J Appl Polym Sci 1984;29:2829–42. Fambri L et al, Biodegradable fibres. Poly l-lactic acid fibres produced by solution spinning. J Mater Sci Mater Med 1994;5:679–83. Melt spinning and solution spinning of PLA fibres 1994: Kanebo (Japan) LACTRON fibre and spun-laid nonwovens
- 54. hydrolytic degradation due to ester linkage Esterase enzymes Degradation 2-4 weeks Acid induced inflammation Degradation of PGA glycolic acid is metabolized into water and CO2 subsequently cleared by respiration enzymatic conversion of GA into glyoxylate followed by glycine. degrade primarily by bulk erosion
- 55. Polycaprolactone Synthesis from ε-caprolactone monomer achieved by: Anionic polymerization, Cationic polymerization, Coordination polymerization Free-radical polymerization
- 56. can be degraded by (a) hydrolytic mechanism (b) enzymatic surface erosion PCL degrades at significant lower rate than PLA, PGA, PLGA Low-molecular-weight fragments of PCL are taken up by macrophages and intracellularly degraded
- 57. synthesized by addition of polyols to diketene acetals or by diol and diethoxytetrahydrofuran transesterification Degradation is through hydrolysis of ester backbone generation of diols ………….. acidic levels significantly lower than PLGA. Degradation is pH sensitive. At physiological pH, POEs are stable POE hydrolysis cause surface erosion as a result of the hydrophobic hydrocarbon–ether ring Polyorthoesters
- 58. Tough elastomers, hard and soft segments Polyurethanes
- 59. Regenerated Cellulose Viscose, CMC Cellulose produced by microorganisms (bacterium Gluconacetobacter xylinus). Unique properties of Bacterial cellulose: biocompatibility, high water-holding capacity, high crystallinity, high tensile strength in the wet state, a fine fibre network structure. Cellulose dissolved in a solvent (e.g., ammonia/ammonium thiocyanate, calcium and sodium thiocyanate, zinc chloride, dimethylacetamide/lithium chloride, N-methyl- morpholine-N-oxide, aqueous solution of NaOH, aqueous NaOH/urea, NaOH/thiourea, DMSO/paraformaldehyde. Hemodialysis membrane
- 60. Factors affecting degradation of polymeric fibres Characteristics of polymer • Chemical str • Mol wt & distribution • Crystallinity • Additives, impurities Processing • Superficial morphology • Thermal treatment • Sterilization method Degradation medium • Site of application or implantation • pH • Enzymes • macrophages (i) Surface erosion mechanism : starts on the exterior fiber surface & continues until the fiber has been totally absorbed (ii) Bulk erosion mechanism : autocatalytic process & starts in the center of fiber.
- 61. Factors controlling polymer degradation and erosion Bulk erosion Surface erosion Mol wt reduces with time Dimension same until collapse Ingress of water is faster than the rate of degradation Mol wt constant Linear loss of mass from surface Mass loss is faster than the ingress of water into the bulk poly(ortho)esters, polyanhydrides PLA, PGA, PLGA, PCL
- 62. Bond stability Amide Esters ortho esters anhydrides Hydrophobicity Steric effects Porosity Crystallinity, phase separation Factors controlling polymer degradation rates A. Gopferich, Mechanisms of polymer degradation and erosion. Biomaterials 17, (1996), 103-14
- 64. 4 hours 6 hours
- 65. 18 hours 24 hours High Cell density low Cell density Myeloid cell differentiation..―niche‖ for tissue regeneration ????
- 66. Design criteria of Medical textile products
- 67. Design criteria Nonwoven: Air-Laid, wet laid Knitted : warp knitted, weft knitted braids, electrospun, Composites • Textile architectures that simulate desired anatomical features (orientation) desired mechanical properties desired biological properties • Cost effectivity Woven : plain, twill, satin weaves, 3D weaving • Understanding of the tissue into which it will be applied • Fibre Chemistries that regulate selected cell functions
- 68. • Chemical – Biodegradability – Initially facilitate cell attachment (integrin) – Affect cell functions such as mitosis, biosynthesis • Mechanical – Strength – Modulus of elasticity; stiffness • Physical – Porosity Which polymer ?
- 69. Which method of Textile Eng ?
- 70. Woven fabrics typically are stronger can be fabricated with lower porosities or lower water/blood permeability, compared to knits Knits have higher permeability than woven designs are easier to suture, but may dilate after implantation. Braids have high flexibility, but can be unstable except when subject to longitudinal load, as in the case of a suture. Multilayer braids are more stable, but are also thicker & less flexible than unidimensional braids. Embroidered structure Which method of Textile Eng ?
- 71. Braids suture materials, vascular graft and ligament prostheses. Common braided structures involve the interlacing of an even number of yarns, leading to diamond, regular, and Hercules structures that can be either 2D or 3D.
- 72. As the yarns criss-cross each other, braided textiles are highly porous and retain fluids within interstitial spaces between yarns (optional) coating of biodegradable or nonbiodegradable polymers (Teflon) Smoothness Reduce capillarity, porosity Analysis of Polymeric Braided Tubular Structures Intended for Medical Applications Mehmet E. Yuksekkaya and Sabi Adanur Textile Research Journal, Feb 2009; 79: pp. 99 - 109.
- 73. Nonwovens Textile structure produced directly from fibers without the intermediate step of yarn production. The fibers are either bonded or interlocked together by means of mechanical or thermal action, or by using an adhesive or solvent or a combination these approaches. Properties are governed by the polymer/fibre characteristics & bonding process The fibers may be oriented randomly or preferentially in one or more directions, and by combining multiple layers one can engineer the mechanical properties independently in the machine (lengthwise) and cross directions.
- 74. High surface area Very high fluid repellency or absorbency Extremely low linting Fast wicking of liquids Average pore size of a nonwoven web depends on density of fibers, & average fiber diameter, and falls under a single distribution. That is why most of the tissue-engineered scaffolds are nonwovens.
- 75. Knitted Knitted constructions are made by interloping yarns in horizontal rows and vertical columns of stitches. They are softer, highly porous, more flexible and easily conformable, and have better handling characteristics than woven graft designs. Knit fabrics can have high water permeability values (5,000 ml cm−2 min−1 ) and still maintain structural stability. Warp knit is less stretch than weft knits, Warp knits do not run and unravel when cut at an angle . highly porous grafts materials are usually coated or impregnated with collagen or gelatin so that the surgeon does not have to perform the time consuming pre-clotting process at the time of surgery.
- 76. When knits are produced, the fabric is typically very open and requires special processing to tighten the looped structure and lower its permeability. This compaction process is usually done using a chemical shrinking agent such as methylene chloride or by thermal shrinking. Because of their open structure, knits are typically easier to suture and have better handling characteristics Limitation: Unlike woven fabrics, high porosity of knitted fabric can not be reduced below a certain value determined by the construction
- 77. Woven Fabrics Yarns (warp, weft) are oriented at 90◦ to each other. Due to orthogonal relationship between the warp and weft, woven structures show low elongation, high breaking strength in both directions. Dimensionally highly stable Limitation: tendency to unravel at the edges when cut squarely / obliquely Leno weave , 3D weave
- 78. Spacer fabrics pressure resistance : fiber material, fiber angle , stitch density Directed fluid transport : Spacer fabrics based bandages (lymphedema of the leg) compression bandage Specialty bed cover
- 79. Wound dressing N. Mao, S.J. Russell, Nonwoven Wound Dressings, Textile Progress, 36, 2004
- 80. Wound is a disruption of normal anatomic structure & function Acute wound / Chronic wound Open / Closed wound Chronic wounds = non healing wounds (diabetic foot Ulcers, bed sores, etc) Functions: to give protection against infection to absorb blood promote healing apply medication to the wound combat odour relieve pain promote autolytic debridement
- 81. Wound healing is defined as a complex dynamic process that results in the restoration of anatomic continuity and function and it usually involves an orderly sequence of biological events Neutrophil : Polymorphonuclear cells which phagocytosise dead cell debris & bacteria Macrophage : Monocytes Macrophages Antigen presenting cells Remove debris, dead cells Synthesis of TGF-β, FGF-2, PDGF, VEGF Fibroblast, Endothelial cell, Keratinocyte
- 83. Our main targets To optimize physiological requirements • Clean the wound bed – remove cell debris, bacteria • Provide moist wound environment • Provide desired pH • Provide optimum O2-CO2% , nutrients • Stimulate immune cells (for chronic wound)- controlled inflammation • Minimal pain and discomfort during dressing change Controlled Wound Inflammation Is beneficial for Chronic wounds
- 84. fibrinogen from blood Fibrin fibre mesh
- 85. Haemostasis Inflammation Proliferation Remodeling Starts immediate up to 2-3 hr Vasoconstriction Platelet activation coagulation Immediate up to 2-5 days Leucocytes (WBC), macrophages Edema, heat, pain After 2-3 days to 2-3 weeks a) Granulation tissue formation b) Angiogenesis (endothelial cells) c) Epithelialisation (keratinocytes) d) Contraction (myofibroblasts) Organized network of collagen fibres Scar tissue: Excessive or too oriented collagen fibres
- 87. superficial wounds involve only the epidermis, partial thickness wounds involve only epidermis and dermis, full thickness wounds involve the subcutaneous fat or deeper tissue
- 88. Platelet activation, coagulation Neutrophil Macrophages Provisional fibrin fibrous martix Granulation tissue formation Fibroblast Growth factor ECM prodn Cell migration Cellular density ↓ Blood supply ↓ Contraction ↑ Collagen orientation ↑ Epithelial thickness ↑ Injury Tissue of Permanent Cells Tissue of Labile & Stable Cells Framework Intact Regeneration Framework Destroyed Scar Scar Inflammation Endothelial cells Protease Epithelialization Keratinocyte
- 89. Severely burned victim heals injury by contraction and scar formation
- 90. A case of skin regeneration studied by Dr. Andrew Byrd, Bristol, UK Burn victim, a female teenager, was treated by 1) excision of burn scar, 2) grafting of a biologically active (Col-GAG) nonwoven fabric , 3) regeneration of skin in place of burn scar Courtesy: Prof M Spector, MIT
- 91. Surgeon has excised the entire scar around breast generating a deep skin wound Wounds have been grafted with the collagen-GAG nonwoven matrix Courtesy: Prof Myron Spector, MIT
- 92. New vascularized skin has grown two weeks after grafting of nonwoven matrix. Two-stage procedure: 1. Graft nonwoven fabric to regenerate dermis. 2. Graft an epidermal autograft on top of new dermis. ―Alligator‖ pattern disappears later Courtesy: Prof M Spector, MIT
- 93. Nonwoven grafted….. No contraction. Contractile fibroblasts are fewer and are also disorganized, leading to cancellation of mechanical forces for contraction No nonwoven... Spontaneous healing of deep skin wound. Contractile fibroblasts (red brown) form thick layer that pulls wound edges together, inducing contraction and closing wound Myofibroblasts contain α-smooth muscle actin in thick bundles called stress fibers
- 94. Mechanism of scar formation 1. Contractile fibroblasts (myofibroblasts) initiate & propagate contraction. 2. Collagen fibers in scar are highly oriented in the plane of the wound. 3. Collagen fibers synthesized by myofibroblasts & extruded outside with fiber axis parallel to long cell axis. 4. Collagen fiber orientation in scar is in the plane of the wound, suggesting that myofibroblasts are in a plane stress field during scar synthesis. 5. Regeneration templates cancel out mechanical field, leading to randomization of myofibroblasts axes & fiber synthesis in random orientation.
- 95. Synthetic Dressings Gauze dressings (non-impregnated or impregnated) · Alginate dressings · Composite dressings · Contact layer dressings · Foam dressings · Hydrocolloid dressings · Hydrogel dressings · Specialty absorptive dressings · Transparent film dressings Biological & Biosynthetic Dressings · Allografts, heterografts, and tissue culture products · Artificial skin Topical Adjuvants · Enzymatic debriding agents · Wound cleansers · Skin sealants, protectants, and moisturizers Novel Products & Technologies · Electrical stimulation · Hyperbaric oxygen · Tissue growth factors · Emerging novel products and technologies · Miscellaneous emerging products
- 96. “closed wounds heal more quickly than open wounds”- Papyrus, 1615 BC (A) Traditional dressings : dry wound management. gauze and gauze dressings, antimicrobial impregnated dressings, adhesive bandages. (B) Occlusive & semi-occlusive dressings : wet wound management. films, foams, hydrocolloids, gels/hydrogels. Dr. George D. Winter (1927-1981) Moist wound environment vapour transmission rate through the dressing is lower than moisture produced within the wound Honey, mud, cobweb, animal fat, leaves, plant extract
- 97. (A)Traditional dressings A bandage is a piece of material used to support a medical device such as a dressing Gauze- cotton mesh or Nonwoven absorbent cotton dressing Woven/ knitted outer layer Gauze keeps other dressings on the wound while slightly compressing it. A tightly woven wound dressing gives a smoother dressing pads and probably absorb more quickly, Looser structure provides more bulk for greater protection of wound from impact
- 98. Disadvantages of simple gauze dressings: Gauze can stick to exudate Is not conducive for healing extremely deep wounds or wounds with irregular shapes Rate of wound healing is slower than occlusive dressings. Unable to absorb large amounts of exudates The pain patients feel from a healing wound is not diminished by gauze. Gauze is not as comfortable to patients as occlusive dressings (hydrogel dressings)
- 99. fibres stick to the wound Major problem of Cotton-based wound dressings
- 100. Cotton gauge dressing soaked with pus caused by bacteria (Pseuodomonus Pyocyania)
- 101. Impregnated gauge • H2O2- a disinfectant • 70% isopropyl alcohol- a disinfectant (can damage granulating tissue) • Saline • Silvadene (silver sulfadiazine) or SulfaMylon- the topical most widely used antimicrobials in hospitals • Sodium hypochlorite (Dakin‘s solution)- an antiseptic non-adherent material, slow decomposing
- 102. Adhesive bandages 1. Flexibility of bandages: is derived from the stretchable fabric. Fabric-backed bandages are inherently more flexible than vinyl/plastic. Johnson & Johnson Kendall 2. Ability to stay on wounds for longer periods. children, who tend to get more cuts and scrapes than adults & are less careful. Band-Aid
- 103. B) Occlusive and semi-occlusive dressings Films Foam Hydrocolloid Hydrogel Biological Composite Smith & Nephew : OpSite 1981 Johnson & Johnson : Band-Aid brand : antibiotic ointment directly on the pad to prevent further infection gauze impregnated with Vaseline oil emulsion Beiersdorf, Tyco 3M : Tegaderm film
- 104. Advantages of semi-occlusive / gel impregnated dressings Do not stick to the wound bed as much as dry gauze. Due to added agent, they promote faster healing and re- epithelialization of a wound. Petroleum emulsion can impart a soothing, comforting feeling Like other gauze bandages, impregnated dressings can be applied easily, are conformable to the body‘s joints and contours, and can be fitted into deeper wounds. Unlike more occlusive dressings, they can be used on an infected wound. Beiersdorf (Aquaphor) Carrington Laboratories, Inc (CarraGauge) Derma Sciences (Dermagran) Davis & Geck (Xeroform) they partially block the passage of air into the wound partly let the moisture (from exudate) from wound pass through film.
- 105. Wound can be visually inspected through the transparent film Film dressings conform to the contours of the body, (e.g., flexible joints, knees or elbows, and the perineal area ) Keeps out bacteria and water while permitting gaseous exchange from the wound. In preclinical and clinical studies, film dressings have increased epidermal healing by 20% - 40% compared with untreated control wounds. Advantages of Film dressings Disadvantages Films do not absorb, so can not be used on deep or heavily exudating wounds Beneath the film accumulation of wound exudate, white blood cells, bacteria, which can produce a foul-smelling pus & maceration of surrounding skin Infection develops in less than one of every 20 wounds covered with film dressings
- 106. Foam dressings Foam dressings have a modified polyurethane core, which absorbs exudate. Three layers consisting of: 1) A nonadherent wound contact layer that is soft enough not to traumatize the wound. 2) The polyurethane foam middle layer. 3) A film outer layer that shields the wound from fluid or bacteria but permits gaseous exchange. Soft, cushion-like feeling Do not melt into the wound like hydrocolloids Foams have a tendency to dry out Smith & Nephew : LYOfoam BMS : Hydrasorb Beiersdorf : Cutinova
- 107. Hydrocolloid dressings No gas exchange, moisture vapor exchange multi-layered construction. 1) the hydrophilic layer, made up of colloidal particles. carboxymethylcellulose, pectin, karaya gum, or guar gum. The exudate, when it comes in contact with this colloidal material, becomes a soft gel which adheres together and separates from the wound. Thus, when the dressing is changed, the exudate lifts off readily, generally without damaging the wound. 3M: Tegasorb BMS : Duoderm, Actiderm
- 108. Gel/hydrogel dressings Alginate Collagen Chitosan-based dressings J&J: Fibracol collagen-alginate ConvaTec: Kaltostat Helitrex Inc : CollaCote Collagen Dressing Bausch & Lomb : Bio-Cor Fydovor Collagen Corneal Shield How to develop Alginate hydrogel dressing having (1) enhanced mechanical strength ? (2) reduced tendency to adhesion to wound surface ?? (3) controlled degradation rate ???
- 109. Fibrous Nonwoven sheet Alginate-PEG hydrogel Top view Cross sectional view Sourabh Ghosh, Alok R. Ray , Manjeet Jassal, Preparation of a new Alginate-based wound dressing material: Patent Number 2002DE00736 CAN 146:408479 AN 2007:299984 Poly(ethylene glycol) : as a surface modifier, low cell adhesion and protein adsorption. Ordered water film surrounding each PEG chain provides a hydrated shell that inhibits protein adsorption PEG-diacrylates are used for photoinitiated cross-linking.
- 110. Degradation studies 0 10 20 30 40 50 60 70 80 90 100 0 5 10 15 20 25 30 35 40 Time (days) Weight loss (%) Alg: PEG= 1:0.2 Alg:PEG=1:0.6 Alg: PEG= 1:1
- 111. 0 50 100 0 15 30 Time (min.) % wt of clot formed Glass Alginate 0 10 20 30 40 50 60 70 Alginate (dry) Alginate (wet) Crosslinked (dry) Crosslinked (wet) Time (min.) Comparative force reqd to lift the gel adhered on chicken skin Thrombus formation study Alginate gels initiate slow clotting compared to glass surface
- 112. Human dermal fibroblasts cultured over covalently crosslinked Alginate-PEG gel- nonwoven composite dressing showed downregulation of integrin expression, indicating reduced cell adhesion Mean fluorescence intensities for expression of integrin subunit α1 α2 β1 Collagen coated Petri dish Collagen coated only alginate dressing Collagen coated covalently crosslinked Alginate-PEG hydrogel based dressing IgG control Integrin expression Covalently crosslinked alginate gel Expression of integrin subunit (MFI) 1 2 b1 Collagen coated Petridish 9.9 10.1 31.6 Only Ionically crosslinked alginate gel 3.8 9.8 19.4 1.9 3.4 4.6
- 113. Tissupor Embroidered wound dressing ETH Zurich, Switzerland E Karamuk et al, PhD thesis stitching patterns create wide variation in design
- 116. Tissue-engineered biological dressings Artificial skin from polymer mesh for second- and third-degree burns Apligraf (formerly Graftskin and Living Skin Equivalent), developed by Organogenesis Inc., MA Dermagraft Adv: • promote dermal regeneration • permanent wound coverings • improve cosmetic results, reducing scarring Disadv: • Very high cost makes them feasible only in severe burn patients, refractory chronic wounds • Special expertise is required to prepare & implant them
- 117. Standard testing for wound dressings 1) Define structure and composition 2) Performance standards 3) Safety standards 1907 : British Pharmaceutical Codex – 80 healthcare products 1864, 1968 : British Pharmacopeia FDA American Society for Testing and Materials (ASTM)
- 118. 1) Exudate management BS EN 13726 – 1: 2002 Test methods for Primary wound dressing Part 1: Aspects of absorbency 40 times weight of test sample held for 30 min, 37 oC Allowed to drain for 30 sec Reweighed Absorbancy = mass of solution retained per 100 cm2 (for sheet dressing) Or per gram of sample for nonwoven cavity dressing Test solution: mixture of NaCl (142 mM of Na+ ions) + CaCl2 (2.25 mM of Ca2+) (a) Free swell absorption capacity
- 119. (b) Fluid handling capacity Cylinder with internal cross section area 10 cm2 20 ml of test fluid is added & weighed Cup is placed in incubator (37 oC), RH (< 20%) After 24 hr cylinder is reweighed, plate is removed, excess fluid is drained, cylinder is reweighed Fluid handling capacity = amount of fluid lost through back of dressing by evaporation + weight of fluid retained within the structure (absorbency capability) Paddington cup : http://www.worldwidewounds.com/1997/july/Thomas-Hydronet/hydronet.html (MVTR of a wound dressing)
- 120. (c) Moisture vapour transmission rate BS EN 13726 – 2: 2002 Test methods for Primary wound dressing Part 2: Moisture vapour transmission rate of permeable film dressings ASTM F1249 Normal human skin = 204 +/- 12 gm / m2 / day Dry skin = 215 gm / m2 / day wet skin = 350 gm / m2 / day Injured skin (first degree burn) = 279 +/- 26 gm / m2 / day Deep injury = 5138 gm / m2 / day ASTM E96-80
- 121. Wettability / absorbency A metal plate with a small depression in the centre A weight is applied to the back of dressing W Test fluid is applied by a peristaltic pump or syringe driver Venous leg ulcer dressings need pressure as high as 40 mm Hg Effect of Fibre / Fabric pre-treatment ? Fibre alignment angle ??
- 122. 2. Extent of adherence test Pain is the most common problem during dressing change Alginate, hydrogel, Silicone product Surgical Materials Testing Laboratory (SMTL) Pharm J, 1982, 228, 576- 578 Cold cure silicone rubber Textile dressing W Gelatin
- 123. 3. Conformability test Bandages tend to accommodate changes in body geometry quickly Hydrogels, composites ??? 25 mm 100 mm BS EN 13726 - 4 Extensibility & permanent set conformability 20% const traverse rate 300 mm / min Maxm load is recorded, Sample is hold for 1 min Allow to relax for 300 sec and remeasure 3 % to 20 % Stretchable (better behaviour on joint areas)
- 124. 3. Microbiological test Staphylococcus aureus, Beta-hemolytic Streptococcus (S. pyogenes, S. agalactiae), E. coli, Proteus, Klebsiella, anaerobes, Pseudomonas, Acinetobacter, Stenotrophomonas (Xanthomonas). Streptococcus and S. aureus are common organisms found in diabetic foot ulcers
- 125. Strategies 1. Dressings containing antibiotics, antiseptics, Silver ions, Iodine etc released from dressing 2. Antimicrobials are chemically immobilized on Fibres not released from dressing Am. Asso. of Textile Chemists & Colorists ASTM E 2149-101 Silver and Iodine are well suited to avoiding the development of resistance as they are both fast acting and hit multiple targets.
- 126. 1. Sterile Dressing vertically clamped between two glass hemispheres filled with nutrient broth. 2. Broth in contact with one surface of the dressing is inoculated with selected bacterial strain. 3. Incubated 4. Broth in other side of dressing sampled regularly and checked for the presence of the test bacterium. No visible microbial growth efficient anti-bacterial dressing
- 127. Zone of inhibition Size of ZOI is determined by conc & solubility of active ingredients
- 128. 4. Biological test 5. In vitro cytotoxicity 6. Drug / soluble factor release kinetics 7. Degradation rate
- 129. Suture Technical yarns, Woodhead publishing
- 130. Susruta Samhita (600 BC ??) CHAPTER XVI: The surgeon should then diligently suture up the two edges of the incisions with (horse's) hair.. stitching hair should be carefully removed after the complete adhesion of the Two edges of the ulcer, on 5th day. Sevanis
- 131. Catgut: The tough membrane of sheep intestine was provided to the surgeon pre-sterilised and required threading through the eye of the needle before use. Cattlegut / Kit Post World War II used swaged-on needle. The thread fits into the hollow end of needle, allowing it to pass through tissue without double loop of thread that exists with a conventional needle, reducing tissue trauma. flax, hair, grass, cotton, silk In Egypt „ydr‟ = sutures. ―…. ydr coming loose…‖, ―…finding ydr sticking in the lips of wound..‖ A History of Medicine, by Plinio Prioreschi (Horatius Press, 2002) South America Africa
- 132. The catgut manufacturing process of Franz Kuhn, 1866–1929, World J Surg (2007) 31:2275–2283 Bowl-desk for twisting cords 3-4 days K2CO3 8-10 days I2
- 133. Surgical suture Absorption ability Origin Configuration Absorbable Natural polymers (derived from animals), synthetic polymers Monofilament, multifilament (braided or twisted) composite Non-absorbable Silk, synthetic polymers (nylon), stainless steel Monofilament, multifilament (braided or twisted) composite • Natural or Synthetic • Monofilament or Multifilament (braided) • Absorbable or Non-Absorbable
- 134. Absorbable suture Generic name Raw materials Natural 1. Plain cat gut ( 5-6 days to 2 weeks) 2. Chromic gut (slow degrad) 3. Collagen (plain & chromic) 1. Submucosa sheep intestine 2. Serosa of beef intestine+ buffer chromicizing 3. Beef flexor tendon Synthetics 1. Polyglycolic acid 2. Polyglycolic acid 3. Polyglactine (Vicryl), 1974 4. Polydioxanone (PDS), 1983 5. Polyglyconate (Maxon) 1. Homopolymer of glycolic acid 2. Homopolymer of glycolic acid coated with polycaprolate 3. Copolymer lactide-glycolic acid coated with Calcium stearate , polyglactine 370; braided 4. Polymer of paradioxanone; monofilament (less affi for bacteria, higher disso time, but stiff, difficult to tie) 5. Copolymer of trimethylene carbonate & polyglycolic acid; monofilament, better tying
- 135. Absorbable Sutures Caprosyn Biosyn Maxon Polysorb Dexon II MATERIAL 60% Glycolide 10% caprolactone 10% Trimethylene carbonate 10% Lactide 60% Glycolide 26% Trimethylene carbonate 14% Dioxanone Poly- glyconate 90% Polyglycolic acid 10% Polylactic Acid 100% Polyglycoli c acid STRUCTURE Monofilament Monofilament Mono- filament Braided Braided COATING NA NA NA Caprolactone / Glycolide, Calcium stearoyl lactilate Polycaprol actone TENSILE STRENGTH 10 Days 21 days 42 Days 21 Days 21 Days ABSORPTION PROFILE 56 Days 90-110 Days 180-210 Days 56-70 Days 60-90 Days absorbed through enzymatic, inflammatory reaction or hydrolytic processes within 60 days
- 137. Non-Absorbable Sutures • Permanent • Only used when long term support is required • Removed when used for skin • Tissue reaction generally low (except silk) • However silk, linen and even nylon will lose tensile strength over a period of time • Example: polyester, polyethylene, polybutylester, polypropylene and steel
- 138. Non-absorbable suture Generic name Raw materials Natural fibres 1. Surgical cotton 2. Surgical linen 3. Virgin silk; surgical silk 1. Twisted natural cotton 2. Twisted long-staple flax 3. Natural as spun, untreated; twisted, silicon-impregnated Synthetic fibres 1. Nylon Polyamide 6,6- monofil Polyamide 6,6- braided Polyamide 6-twisted fibres enclosed in a polyamide sheath Polyamide 6,6-silicon treated 2. Polypropylene (Prolene) 3. Polyester Ethibond Monofil; stiff, untying of knot, cutting of tissues Monofil, braided, silicon treated, teflon-coated Polyester coated with Polybutylate
- 139. Braided v Monofilament Has capillary action Increased infection risk Less smooth passage Less tensile strength Better handling Better knot security No capillary action Less infection risk Smooth tissue passage Higher tensile strength Has memory More throws required
- 140. Properties of Suture 1. Physical characteristics: material, surface, length, dia, knot-pull strength, needle attachment force 2. Handling characteristics: mechanical behaviour before, during , after wound closure 3. Biological characteristics: biological responses during, after wound healing USP
- 141. Knot-pull strength: for defining limits of suture knot-failure, related with a specific dia Tensilometer 0.005-9 kg Needle attachment force: Force reqd to separate the needle from the suture Tensilometer 0.007-1.8 kg Knot security: 1. Knot strength, refers to the force reqd to cause a given type of knot to slip 2. Minimal number of throws reqd to establish a stable knot Depends on -- Knotting techniques, materials, friction coeff, compressibility, stiffness. Uncoated > coated ; Braided > monofilament Physical characteristics
- 142. Elasticity: ability of the suture to return to its original state after stretching Plasticity: ability of the suture to retain its new, deformed state Memory: depends on elastic-plastic properties of suture
- 143. Sutures with high memory (nylon) tends to unite, so their knot security is low Sutures with low memory (silk) tends to unite. Monofilament has memory, Multi- has no memory Monofilament Nylon suture showing high memory, resulting in low knot security and will cause undesirable wound dehiscence
- 144. Handling characteristics Knottability: ability to be tied with relative ease by surgeon, & difficulty to unknot flexibility/ pliability, smoothness, coeff of friction, memory Biological characteristics Possibility of infection/ inflammation Braided/ multifilaments > monofilament Coated > uncoated Natural > synthetic Allergy: silk, nylon, Chromate allergy
- 145. Suture Size 5..4..3..2..1…..0….2/0..3/0..4/0..5/0..6/0..7/0..8/0..9/0..10/0..11/0 Thick Thin USP (United States Pharmacopeia) Suture Selection Bowel: 2/0 - 3/0 Fascia: 1 - 0 Ligatures: 0 - 3/0 Pedicles: 2 - 0 Skin: 2/0 - 5/0 Hand : 5/0 Eyelid 6-0 or 7-0 Eyebrow 5-0 or 6-0 Arteries: 2/0 - 8/0 Micro surgery 9/0 - 10/0 Corneal closure: 9/0 - 10/0
- 146. • Minimal tissue reaction • Smoothness - minimum tissue drag • Low Capillarity • Max tensile strength • Ease of handling - Minimum memory • Knot security • Consistency of performance • Predictable performance • Cost effectiveness • Ability to resist bacterial infection Ideal suture
- 147. Disadv of Sutures : 1. risk of infection: The mere act of penetrating the skin opens an avenue for infection, and the presence of a suture further increases the tissue‘s susceptibility to contamination. The sutures least likely to provoke infection are composed of absorbable polymer and animal gut or nonabsorbable nylon and polymers. Nonabsorbable Dacron, stainless steel, and cotton or silk sutures generally carry a greater chance for infection. 2. Sutures can unravel or become loose if they are not tied properly. Successful suturing is heavily dependent on the skill of an individual surgeon
- 148. Macrophages and Giant Cells next to Suture Panacryl sutures, made by Ethicon Inc., JnJ (recall 2006) Vicryl sutures (1996, 1998, 2001, 2002, 2003 and 2004)
- 150. L1 L3 L2
- 151. The suture is able to self-tighten a knot upon immersing into room temperature water without any other interference.
- 152. biologically activating surgical sutures by fixing the appropriate drugs (chemotherapeutic agents) antimicrobial agents inhibitors of proteolytic enzymes inhibitors of MMPs radioactive fibres (in tumour area with minimal injury to subjacent tissues. phosphorus-32 and sulphur-35 will cause local immunosuppressive action by their radiation, and thus suppress foreign body reaction. The half-life of P32 is 14.2 days, of S35 87.9 days. Future direction
- 153. Textile-based & Tissue engineered Blood Vessels Dr Sourabh Ghosh
- 154. 1953 : Dr. Michael DeBakey constructed the first Dacron artificial artery, working at home on his wife's sewing machine 1955 – nylon grafts, crimping (Edvards,Tapp) 1956 – knitted seamless graft made of Orlon fibre 1960s – knitted and woven grafts made of polyester July 2008, Houston Acute thrombogenicity, anastomotic intimal hyperplasia, aneurysm formation, infection, progression of atherosclerotic disease 1972: MGH : patency rate at 5 and 10 years Dacron tube has less than 10% patency rate Reversed saphenous vein has 65-70% patency rate at the same time period Hollow glass, metal, and paraffin rod 1906 : The first autologous vein bypass 1952: Voorhees, Jaretski, Blakemore Dog: silk suture covered with endothelial cells Vinyl, nylon, orlon based grafts discarded (progressive loss of tensile strength, shortly after implantation). Today only Dacron is used.
- 155. Woven : 1. UBE. 2. Intervascular Inc. 3. Cooley 4. USCI Knitted: 1. Bionit (Bard Inc.) 2. Cooley double velour. 3. Microvel double velour (Meadox Medical Inc) Photo from Medical Textiles AJ Rigby, SC Anand Embroidery vascular stent Commercially available vascular grafts polyester (e.g. Dacron), PTFE (e.g. Teflon) 1. During implantation the surgeon should bend and adjust the length of the graft, 2. Crimp should allow the graft to retain circular cross-section
- 156. Process • heat set into crimped configuration • Texturized to induce bulkiness- pore str, softness, wall thickness Weft knitted structure: • Poor dimensional stability • Tendency to unravel 1940s: preclot the graft with patients‘ blood Coat with heparin heparin-bonded ePTFE FDA approved impregnation with collagen or gelatin 1990s : Coating or covalent attachment of laminin, fibronectin and heparan sulphate. Dacron activates both the complement and coagulation cascades triggers the release of superoxides and thromboxanes by leukocytes woven grafts are stiffer, less porous than the knitted grafts
- 157. ‗Gold standard‘ is still autologous grafting Urgent need for small size vascular graft: Large diameter (12-38 mm) Medium diameter (5-10 mm) small-diameter (<6 mm) prosthetic vascular grafts: High resistance, low flow Size mismatch zero or nearly zero water permeability of the grafts biocompatibility, blood compatibility, burst pressure, graft stiffness/elasticity to match native vessels, fatigue lifetime , handling characteristics
- 158. Polyglycolic acid, poly-L-lactic acid Exp Cell Res, 1999; 251:318-328. Polyhydroxyalkanoates (poly-4-hydroxybutyrate) Shum-Tim D et al, Tissue engineering of autologous aorta using a new biodegradable polymer. Ann Thorac Surg, 1999; 68 , 2298-2305. polycaprolactone-copolylactic acid Shin‘oka T et al, Transplantation of a tissue-engineered pulmonary artery. N Engl J Med, 2001; 344: 532-523. polyethylene glycol Wake MC et al, Fabrication of pliable biodegradable polymer foams to engineer soft tissues. Cell Transplant, 1996; 5: 465- 473. Silk Zhang X et al, In vitro evaluation of electrospun silk fibroin scaffolds for vascular cell growth , Biomaterials, 29, 14, 2008, 2217-2227 Lovett et al, Silk fibroin microtubes for blood vessel engineering, Biomaterials, 28, 35, 2007, 5271-5279
- 159. knitted vascular graft made of biologically inert polyester fibre and coated on the outer side with a continuous film of chemically modified bovine collagen of type I
- 160. • Cardiovascular tissues / Blood Vessels –– Endothelium - smooth muscle - connective tissue type I and III collagens elastin type IV collagen, laminin, and perlecan
- 161. Endothelial cells ( lining by perfusion flow (~40 µm/s)) Smooth muscle cells 1. Fabrication of blood vessels- scaffold characterization 2. Uniform seeding of 2 different cell lines- application of perfusion bioreactor Construct at day 6 On line imaging Tissue engineered Blood vessel Biomaterials. 2007 ; 28(35) :5271-9 Burst pressures for the microtubes of lower porosities were very high average burst pressure 2780±876 mmHg 100/0 wt% silk fibroin/PEO 2470±937 mmHg 99/1 wt% silk fibroin/PEO 2460±844 mmHg 98/2 wt% silk fibroin/PEO human saphenous veins (1680 ± 307mmHg)
- 162. Electrospun nanofibrous tubular blood vessel DC Motor Silk Fibroin Solution Human aortic endothelial cell Human coronary artery smooth muscle cell human saphenous veins (1680 ± 307 mmHg 1028 ± 256 mmHg
- 163. MCAM platelet endothelial cell adhesion molecule platelet endothelial cell adhesion molecule
- 164. Future direction • Adhesion of EC to the biomaterial requires pre-adsorption of adhesion macromolecules, such as fibronectin, laminin 2. EC adhesion is RGD-dependent 3. Controlled branching 4. EC- SMC interaction Immortalization of human microvascular endothelial cells : Transfection of primary pulmonary microvascular EC with (1) Plasmids containing the large T antigen of SV40 (2) sequentially the catalytic component of the TERT gene, involved in controlling cellular senescence