Slides for class.pdf

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

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%

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

• 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

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

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)

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

‗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.

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

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

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

Healthcare
products
Medical Textiles
Non- Implantable
materials
Implantable
materials
Scaffolds for
Tissue
engineering
Suture
Hernia mesh
Vascular graft
Gown
Mask
Incontinence
Sensors

Knitted heart valve
developed at IITD
Commercially
available valve

• 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

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)

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

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

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.

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

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).

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

three polypeptide chains assembled into a rigid triple helix
The strength of collagen
macromolecule comes from the
hydrogen bonds between the α-chains

Metalloprotein enzyme Collagenase degrades
collagen fibers.
Melting of collagen to gelatin (loss of
tertiary structure) spontaneously follows
such degradation.

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.

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.

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)

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

(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 ?

Nephila clavipes (spider silk)
Bombyx mori silkworm

random-coil
silk I
alpha-helical conformations
5-10% silk II beta-sheet

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

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)

Ca2+ Ca2+ Ca2+ Ca2+
Ca2+
Ca2+
Ca2+
Egg box model
Ca2+

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

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

Chitosan
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
Chitin,
poly β(14)-2-acetoamido-2-deoxy- D-glucopyranose
Deacetylation of chitin by alkali
generates chitosan
crustacean, insects, fungi, yeasts

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

‗‗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

—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

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.

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

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

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

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

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

Polycaprolactone
Synthesis from ε-caprolactone monomer achieved by:
Anionic polymerization,
Cationic polymerization,
Coordination polymerization
Free-radical polymerization

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

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

Tough elastomers, hard and soft segments
Polyurethanes

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

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.

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

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

http://www.city.ac.uk/optometry
lymphocyte
macrophage
Streptococcus

18 hours 24 hours
High
Cell
density
low
Cell
density
Myeloid cell differentiation..―niche‖ for tissue
regeneration ????

Design criteria of
Medical textile products

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

• Chemical
– Biodegradability
– Initially facilitate cell attachment (integrin)
– Affect cell functions such as mitosis, biosynthesis
• Mechanical
– Strength
– Modulus of elasticity; stiffness
• Physical
– Porosity
Which polymer ?

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 ?

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.

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.

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.

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.

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.

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

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

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

Wound dressing
N. Mao, S.J. Russell, Nonwoven Wound Dressings,
Textile Progress, 36, 2004

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

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

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

fibrinogen from blood Fibrin fibre mesh

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

superficial wounds involve only the epidermis,
partial thickness wounds involve only epidermis and dermis,
full thickness wounds involve the subcutaneous fat or
deeper tissue

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

Severely burned
victim heals injury
by contraction and
scar formation

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

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

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

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

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.

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

“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

(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

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)

fibres stick to the wound
Major problem of Cotton-based wound dressings

Cotton gauge dressing soaked with pus caused by bacteria
(Pseuodomonus Pyocyania)

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

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

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

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.

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

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

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

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 ???

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.

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

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

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

Tissupor Embroidered wound dressing
ETH Zurich, Switzerland
E Karamuk et al, PhD thesis
stitching patterns create wide variation in design

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

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)

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

(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)

(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

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 ??

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

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)

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

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.

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

Zone of inhibition
Size of ZOI is determined by conc & solubility of active
ingredients

4. Biological test
5. In vitro cytotoxicity
6. Drug / soluble factor release kinetics
7. Degradation rate

Suture
Technical yarns, Woodhead publishing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

• 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

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

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)

The suture is able to self-tighten a knot upon immersing into room
temperature water without any other interference.

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

Textile-based & Tissue engineered
Blood Vessels
Dr Sourabh Ghosh

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.

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

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

‗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

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

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

• Cardiovascular tissues / Blood Vessels
–– Endothelium - smooth muscle - connective tissue
type I and III
collagens
elastin
type IV collagen,
laminin, and
perlecan

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
human saphenous veins (1680 ± 307mmHg)

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

MCAM
platelet endothelial cell adhesion molecule
platelet
endothelial
cell
adhesion
molecule

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

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