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1/10/2011
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TTL 746
Medical Textiles
Higher expectations of quality of life
Rising standards of living
Changing attitude
2004: number of people aged over 60 amounts to 40% of the entire population.
Textile products that have been engineered tomeet specific needs of suitable medical &surgical applications, related to hygiene &healthcare
p p2009: 66.57 years
Minor 1
Overview‐ Classification of Med Textile fieldPolymers & fibres Design criteria & fabrication methodsNon‐implantable materials: Wound dressing, Bandages, GaugesImplantable biomedical devices: Hernia mesh, Vascular grafts, Sutures, Heart valves
Minor 2Scaffolds for Tissue Engineering :Cartilage (nonwoven, 3D weaving) , Skin (nonwoven, weaving) , Liver
(rapid prototyping) Kidney Urinary bladder (nonwoven 3D weaving)(rapid prototyping) , Kidney, Urinary bladder (nonwoven, 3D weaving) , Tendons, Ligaments (Silk filaments, braiding), Cornea
Major
Healthcare & hygiene products: Surgical Gown, mask, wipes, AntibacterialTextile, Super absorbent polymer, Dialysis, adhesive, anti‐adhesive patches forSurgical application, Hollow fibre bioreactors, Coating & finishing technologies
Characterizing tests, Evaluation of commercial Med Textiles products, Standards….. Legal & ethical issues
Course structure
Minor 1: 25%
Minor 2: 25% (Open book)
Major: 35 40%
Term Paper : students should identify existing specific clinical problems of any Medical Textile product, & propose novel solutions using ‘smart’ Medical Textiles.
(3 students per group)
Major: 35‐ 40%
Quiz, Term report: 10‐15%
• Papers to be distributed in class
• Medical Textiles, by Subhash Anand,Woodhead Publishing Ltd
• Medical Textiles and Biomaterials for Healthcare, Edby S.C. Anand, M Miraftab, JF Kennedy, Woodhead Publishing Ltd,2005
• Medical Textile monthly newsletters, Technical Textiles NetPublications
• Medical Textiles 2007: Proceedings of 4th Int conf on healthcare andmedical 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
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
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1. TISSUE ENGINEERS2. GENE PROGRAMMERS 3. Genetic Eng FARMERS
...and which jobs will disappear?
Teachers
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
Market size of Technical textiles in India Tata Economic Consultancy Services road map for Indian Technical Textile sector
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
‘Technical Textiles and Industrial Nonwovens: World Market Forecast to 2010’ published by David Rigby Associates
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)
• Consumption is increasing rapidly• Private Hospitals, Health centres are rapidly growing•Doctors/patients’ awareness for hygiene is increasing• Medical tourism
Why Textiles should be used for Medical purpose?
1. Combinations of variety of designs – Fibre, yarns, polymers
Greater freedom to optimize design and performance
2 Easy handling manipulation by surgeon2. Easy handling, manipulation by surgeon
3. Flexibility, supplenss, mechanical strength similar to soft tissues
4. Fatigue resistance to survive dynamic motions inside body
5. Porous structures of fabric will allow tissue in growth
Use of Textile‐based constructs for Med Textile & Tissue eng
Major challenges ahead:
Safe but cheaper solutions
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
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What Constitutes Medical Textiles ?
Polymers (& Liq crystals, hydrogels)– Biocompatible
Chemicals – Medical Products
Fibres & Yarns ‐ Normal, Functional
Fabrics – Woven, Non‐woven, Knitted, Braided
F b i ti T h i M ldi C tiFabrication Techniques – Molding, Casting
Products and Technologies
Chemistry, Fibre Technol, Textile Engineering, Mechanical Eng, Computer Sci,
Product development, Biology, Biotechnology, Instrumentation & Biomed Eng
Healthcareproducts
Medical Textiles
Non‐ Implantablematerials
Implantablematerials
Scaffolds for Tissue
engineering
Suture
engineering
Non‐implantable materials Implantable materials
LiverLiver(Rapid prototyping)
Kid U i bl ddKid U i bl dd
CorneaCornea(Knitting, Electrospinning,Hydrogel composite)
MuscleMuscle(Electrospinning, Knitting,
Fibrous composite)
Blood vesselsBlood vessels(Electrospinning, Knitting, Braiding)
Cardiac tissueCardiac tissue(knitting)
NerveNerve
Tendons, LigamentsTendons, Ligaments(Mono/multi-filaments, Braiding)
CartilageCartilage(Nonwoven, 3D weaving)
Kidney, Urinary bladderKidney, Urinary bladder(Nonwoven, 3D weaving)
(Nonwoven, Weaving)SkinSkin
NerveNerve(Electrospinning,
Rapid prototyping)
Sewing ring fabric
Examples of some exciting Medical Textiles
Knitted heart valvedeveloped at IITD
Commercially available valve
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Cardiac Constraint sock for congestive heart failure
Acorn cardiovascular Inc
Polypropylene or polyester mesh used for hernioplasty and pelvic floor surgery
Biocompatible Polymers
Ease of processing ‐ versatility of optionsImprove 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)
Fibres are present even within a cell !!
Globular Proteins Fibrous Proteins
Fibrous proteins are insoluble in water, due to a high percentage of hydrophobic amino acids in their primary structures.
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 LibriAndreas Vesalius (1514–1564)
1543 BaselSwitzerland
Collagen fibreNerve fibresElastinfibresMuscle fibres
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Courtesy: Prof M Spector, MIT
Collagen fibres in Extra cellular matrix of cartilage
The major ECM molecules present in tissues
1. Collagen fibres.
2 Elastinfibres2. Elastinfibres.
3. Proteoglycans and glycosaminoglycans (GAGs).
4. Cell‐adhesion molecules (fibronectin, laminin, etc).
5. Water (about 65%).
Protein fibres are polymers of amino acids
Two amino acids can be covalently joined by a amide linkage (Peptide Bond)30% of the human proteins consist of collagen
Collagen is the basic building material of fibrous connective tissue of living organisms.
Orientation of collagen fibres determines the mechanical behavior of the tissue.
Uniaxialorientation in tendon, ligamentRandom orientation in skin
wavy fiber morphology gives extensibility
Parallelyoriented collagen fibres Randomly oriented collagen fibres on skin
Bone is a composite-hydroxyapatite reinforced by collagen
fibers.Large blood vessels are interpenetrating
networks of elastin fibers and collagen fibers.
y p gy g y
Orientation of collagen fibres in Cornea govern transparency Collagen molecules produced by the cells self‐assemble into fibres.These fibres provide functional integrity of tissues.
Cells in our body produce small collagen fibres
Characteristics of collagen fibres: digitation on surface
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Collagen fibresare fibrous proteins with a unique amino acid composition rich in glycine, proline, and hydroxyproline
20 different amino acids…… 6 types of collagen fibres.
Collagen I : striated fibres…….. Blood vessel wall, tendons, ligaments, bonebone
80‐160 nm in diahigh 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 matrixRamachandran plot is a way to visualize dihedral angles phi against psi of amino residues in protein structures. it shows the possible conformation of of phi and psi
angles for a polypeptide.
Gopalasamudram Narayana Iyer Ramachandran (1922-2001)
Primary structure: complete sequence of amino acids in the polypeptide chain. Scale: 1 nm.
Secondary structure: single peptide stands that are fold to recurring structural patterns.…..Alpha‐helix, beta‐sheet, beta‐turn Scale: 10 nm
Tertiary structure: 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: Several collagen molecules pack side‐by‐side in a highly specific register to give a crystalline fiber with a 64 to 67‐nm periodicity (collagen banding pattern)….. H-bonding, salt bridges, disulfide bonds
Differences in protein function result from differences in amino acid composition and sequence.
Metalloprotein enzyme Collagenase degrades collagen fibers.
Melting of collagen to gelatin (loss of tertiary structure) spontaneously follows such degradation.
collagen fibrils: 10-300 nm
Collagen fibres: few μm
Mechanism of collagen fibril assembly
C- terminal propeptidesN-terminal
by pro-peptidase enzyme
Intracellular : mRNA - Endoplasmic Reticulum- protein synthesis-3 proto-alpha- chains form soluble procollagen
Extracellular
Elastin fibres
fibrous protein acts to impart elasticity and resilience to tissue
Present in walls of large arteries, lungs, skin
It is more compliant than collagenYoung’s mod 3 X 109 Pa
A network of randomly coiled macromolecules ( glycine, proline, but no hydroxylysine ) .
Highly extensible chains: alternating stretchy hydrophobic segments of beta-structure & rigid hydophilic segments of alpha-helix structure
Stretching of elastin fibers leads to large entropy loss due to reduction in chain configurations & increased “ordering” of water molecules against nonpolar amino acids. Spontaneous retraction
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Silk
PupaPupa
FibroinFibroin(protein)(protein)
20~30 20~30 μμmm
SericinSericin(protein)(protein)
alanine, glycine-alanine, glycine-alanine-serine
primary sequences and secondary structures
crystalline β-sheets: contribute to the high tensile strength of silk fibersβ-turn, helical structures: provide elasticity
Silk
PEO
DIAMETER <100 μm microns
CRYSTALLINITY
MORPHOLOGY – surface area
Processing Options for Protein
Processing Options
Courtsey: Prof D Kaplan, Tufts
Silica
hydroxyapatite
CHEMICAL DECORATION ‐ cell functions ‐
MINERALIZATION –composites ‐
β‐sheets
BiomaterialsProtein‐Based Biomaterials – silk
BMP2RGD
(i) Biocompatibility: Silk sutures (FDA approved), biocompatible, less immunogenic and inflammatory than collagens or polyesters such as PLGA
(ii) Stability &Mechanical Properties: remarkable strength & toughness, compressive strength and modulus…… which exceed other commonly used degradable polymeric biomaterials.
thermal stability ‐ can be autoclaved without loss of mechanical integrity
Why Silk is suitable for Medical applications ?
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)
Alginate Seaweed – brown algaeAzotobactervinelandii, Pseudomonas
Fibrepropertiesdepend on ratio of G and M High G contentgivesmorebrittlegels, not good forfibreproduction.High M contentgivesmoreelasticgels.
Egg box model
Ca2+ Ca2+ Ca2+ Ca2+
Ca2+
Ca2+Ca2+
Ca2+
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Seaweed + 0.1‐ 0.2 N mineral acid
Neutralization with NaOH
Precipitation in CaCl2 Parameters: NaCl/CaCl2 ratio, Exposure time,
Method of isolation
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 )
Concentration & mol weight of modifiers
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
Chitosan
Chitin, poly[ β(1→4)‐2‐acetoamido‐2‐deoxy‐ D‐glucopyranose]
crustacean, insects, fungi, yeasts
poly[ β(1→4)‐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
Deacetylation of chitin by alkali generates chitosan
chitosan dissolved in aq. 1‐2% (v/v) acetic acid by stirring at room temp overnight.
Method of isolation
Waste crab shellDil NaOH
Deproteinization DemineralizationDil acid
DecolorationChitinChitosan
Method of Chitosan fibre preparation
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.
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.
Hudson SM, Review of Chitin and Chitosan as fibre and film formers, J Mater Sci, Mater Med, C34(3) 375‐437, 1994
‘‘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
Chitin and chitosan can be degraded by Lysozyme, Papain which acts slowly to depolymerise the polysaccharide.
Chitosan is known to degrade in human serum in vitro.
The biodegradation rate of the polymer is determined by the amount of residual acetyl content.
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Hyaluronic acid
Fidia Advanced Biopolymers, Italy
Hyaff‐11: an esterified form of hyaluronan.
The esterification process results in a highly hydrophobic polymer that can be spun, or woven.
Alternating β‐1,4 and β‐1,3 glycosidic bonds
Hyaff‐11 : degradation time of around 40 days
Hyaluronidase
Degradation
During in vivo degradation Hyaff‐11 fibres become more and more hydrophilic,
forming a gel similar to native hyaluronan found in the extracellular matrix.
