hfm fabrication - university of utahpat/courses/biomaterials2006/hfm... · 2006. 3. 31. ·...
TRANSCRIPT
3/30/2006 1
HFM Fabrication-Fiber Spinning
3/30/2006 2
3/30/2006 3
Phase InversionControlled precipitationSolution--> porous solid that is interconnected and traversed by an interpenetrating pore structure which provides channels across the wall structure
3/30/2006 4
DryDry--Jet Wet SpinningJet Wet SpinningSpinnerette
Nonsolvent Stream
Polymer Solution Stream
PolymerSolution
Stream
NonsolventStream
Note: Picture notdrawn to scale
OutflowStream
Nonsolvent Bath
Anatomy of a SpinneretAnatomy of a SpinneretSpinneretSpinneret
PolymerSolution
Stream
NonsolventStream
Note: Picture notdrawn to scale
OutflowStream
HFM
3/30/2006 6
Required ElementsA polymer of sufficient Mw
that is, enough length to provide inter chain entanglement following precipitation and adhesive force to provide the appropriate mechanical properties for a particular application
Polymer & solvent
Miscible non-solvent
Anatomy of a SpinneretAnatomy of a SpinneretSpinneretSpinneret
PolymerSolution
Stream
NonsolventStream
Note: Picture notdrawn to scale
OutflowStream
HFM
3/30/2006 8
Polymer Solution
3/30/2006 9
The Addition of Non-solvent
3/30/2006 10
Precipitation with Chain Entanglement
Anatomy of a SpinneretAnatomy of a SpinneretSpinneretSpinneret
PolymerSolution
Stream
NonsolventStream
Note: Picture notdrawn to scale
OutflowStream
HFM
HFM
Various Various Stages in Stages in the Early the Early Life of a Life of a HFMHFM
3/30/2006 13
Lumen of Hollow Fiber
Dense Skin
Polymer Rich Zone
3/30/2006 14
3/30/2006 15
Topography of Selective Skin Layer
PhotodiodePhotodiode
XYZ XYZ piezotranslatorpiezotranslator
Cantilever and Cantilever and Probe TipProbe Tip
LaserLaser
3/30/2006 16
Inner Skin Ultra-topography
4° C - 100% H20 Quench
54° C - 100% H20 Quench1000 x 1000 nm
54° C - 50/50 DMF/H20 Quench
22° C - 100% H20 Quench
35
nm
0
3/30/2006 18
Lumen of Hollow Fiber
Dense Skin
Polymer Rich Zone
3/30/2006 19
Production Spinning Line
3/30/2006 20
CC
EE
BB
AAGGDD
FF
HHA A PANPAN--PVC Li et al. 1998PVC Li et al. 1998B B PANPAN--PVC Li et al. 1998PVC Li et al. 1998C C Polyimide Chung et al. 1992Polyimide Chung et al. 1992D D PolysulfonePolysulfone ValetteValette et al.1999et al.1999E E Cellulose acetate Cellulose acetate HaoHao et al. 1996et al. 1996F F PAN copolymer PAN copolymer ValetteValette et al.1999et al.1999G G AN69 AN69 ValetteValette et al.1999et al.1999H H PMMA PMMA ValetteValette et al.1999et al.1999
On a Larger Scale Various Structures are Apparent and can On a Larger Scale Various Structures are Apparent and can be controlled by changing Fabrications conditionsbe controlled by changing Fabrications conditions
3/30/2006 21
Nerve Track Repair: Bridging Substrates
3/30/2006 22
Nerve Repair-Entubulation
3/30/2006 23
HydrogelsHydrogels
3/30/2006 24
Definition-water insoluble, three dimensional network of polymeric
chains that are crosslinked;-polymers capable of swelling substantially in aqueous
conditions (eg hydrophilic)-polymeric network in which water is dispersed throughout
the structure-typically in the swollen state the mass fraction of water is
much higher than the mass fraction of polymer.
3/30/2006 25
The Cross-links may be physical or chemical:
++
__
__
__
++
++
by reaction of one or more monomers with pendant functional groupsElectrostatic, hydrogen or van der Waalsinteractions (physical), heating creates a solution;Covalent bonds (chemical)
3/30/2006 26
HydrogelsOne or more highly electronegative atoms which results in charge asymmetry favoring hydrogen bonding with water;hydrophilic nature -dry materials absorb water;By definition, water must constitute at least 10% of the total weight (or volume) for a materials to be a hydrogel;When the content of water exceeds 95% of the total weight (or volume), the hydrogel is said to be superabsorbant;
3/30/2006 27
Hydrogels: Swelling
Degree of swelling can be quantified by:ratio of sample volume in the dry state to sample volume in the swollen state; weight degree of swelling: ratio of the weight of swollen sample to that of the dry sample
3/30/2006 28
Hydrogels:
In a chemically cross-linked hydrogel, all of the polymer chains are connected by covalent bonds to form a network; and, thusThe material can be viewed as one molecule of large size or supramacromolecule;The thermodynamically driven swelling force is counterbalanced by the retractive force of the crosslinkedstructure; The unique property of these gels is there ability to maintain their original shape during and after swelling;Two forces become equal at some point and equilibrium is reached
3/30/2006 29
3/30/2006 30
XerogelsDried hydrogels;Usually clear and swelling in water takes a long time;The swelling behavior is due to slow diffusion of water through the compact polymer chains;A useful property in controlled drug delivery;
3/30/2006 31
Chitosan
3/30/2006 32
Hydrogels: Swelling
Why is the degree of swelling important?solute diffusion coefficient through the hydrogelsurface properties and surface mobilityoptical properties (particularly for contact lens applications)mechanical properties
3/30/2006 33
Hydrogel Forming Polymers
OHO
OH
HO2C
OOHO
NH
HO
O
O
OHO
OH
NaO2C
O
npoly(hyaluronic acid) poly(sodium alginate)
n
Natural
Synthetic
O
O
nNHOn O
n
poly(ethylene glycol)poly(lactic acid) poly(N-isopropyl acrylamide)
3/30/2006 34
Fibrin Hydrogel (Blood Clot)
3/30/2006 35
HydrogelsHighly swollen hydrogels:
cellulose derivativespoly(vinyl alcohol)poly(N-vinyl 2-pyrrolidone), PNVPpoly(ethyleneoxide)
Moderately or poorly swollen hydrogels:poly(hydroxyethyl methacrylate), PHEMA and derivatives
One may copolymerize a highly hydrophilic monomer with other less hydrophilic monomers to achieve
desired swelling properties
3/30/2006 36
Examples of biological hydrogels:
Jello (a collagen gel ~ 97% water)Extracellular matrix componentsPolysaccharidesDNA/RNABlood clotMucin - lining the stomach, bronchial tubes, intestinesGycocalyx - lining epithelial cells of blood vesselsSinus secretions
3/30/2006 37
Function of a biological hydrogelDecreased permeability to large moleculesStructural strength (for epithelial cell walls)Capture and clearance of foreign substancesDecreased resistance to sliding/glidingHigh internal viscosity (low washout)
3/30/2006 38
Hylauronic Acid
3/30/2006 39
Polyelectrolyte Hydrogels
3/30/2006 40
Polyelectrolyte MultilayersLayer by layer deposition
3/30/2006 41
Alginate gels
3/30/2006 42
Alginate gels
3/30/2006 43
Enzyme Immobilization
3/30/2006 44
Cell Encapsulation
3/30/2006 45
3/30/2006 46
3/30/2006 47
Applications Pharmaceutical applications
monomer composition and relative amounts of multi-polymer hydrogels can be varied to alter the diffusion characteristics; and permeability of the gel containing pharmaceutical agents
Deliverydrug gets trapped in the hydrogel during polymerizationdrug introduced during swelling in waterRelease occurs by outflow of drug from the gel and inflow of water to the gel
3/30/2006 48
Drug delivery
3/30/2006 49
Applications in Biomaterials and Tissue Engineering
Cell EncapsulationDrug delivery Surface modificationEnzyme Immobilization Biosensors Lab on a chip
3/30/2006 50
Hydrogels: ApplicationsBiomedical use due to bio- and blood-compatibilityPharmaceutical use due to hydrophilicity (controlled/sustained drug release)Earliest biomedical application contact lenses
good mechanical stabilityfavorable refractive indexhigh oxygen permeabilityneeds hygienic maintenanceunable to correct for astigmatism
lubricating surface coatingused with catheters, drainage tubes and glovesnon-toxic
3/30/2006 51
Corning® Ultra Low Attachment ProductsUnique hydrogel surface inhibits cell
attachment
3/30/2006 52
Important features of hydrogelsUsually comprised of highly polyionic polymersOften exhibit large volumetric changes eg. Highly compressed in secretory vessicle and expand rapidly and dramatically on releaseCan undergo volumetric phase transitions in response to ionic concentrations (Ca++, H+), temperature, ..Volume is determined by combination of attractive and repulsive forces:
repulsive electrostatic, hydrophobicattractive, hydrogen binding, cross-linking
3/30/2006 53
Hydrogel Forming Polymers
OHO
OH
HO2C
OOHO
NH
HO
O
O
OHO
OH
NaO2C
O
OO
O
NHO
npoly(hyaluronic acid) poly(sodium alginate)
n
n
poly(ethylene glycol)
n
poly(lactic acid)
n
poly(N-isopropyl acrylamide)
Natural
Synthetic
3/30/2006 54
HydrogelsHydrogels //Applications in Applications in OpthamologyOpthamology
3/30/2006 55
Hydrogels: Applications
Earliest biomedical application contact lensesgood mechanical stabilityfavorable refractive indexhigh oxygen permeabilityneeds hygienic maintenanceunable to correct for astigmatism
3/30/2006 56
Acrylates
3/30/2006 57
Methacrylates
3/30/2006 58
Poly(methyl methacrylate)
3/30/2006 59
3/30/2006 60
3/30/2006 61
Poly(2-hydroxyethylmethacrylatepHEMA
3/30/2006 62
Hydrogels: PHEMA
The most widely used hydrogelwater content similar to living tissuesinert to biological processesshows resistance to degradationpermeable to metabolitesnot absorbed by the bodywithstands sterilization by heatprepared in various shaped and forms
3/30/2006 63
Contact lensPMMAHEMAFabrication methods
Computer assisted cutting (lathe)-PMMA rodsSpin casting-polymerization Molding-polymerization
3/30/2006 64
3/30/2006 65
Intraocular lensPMMAHEMAPolymer backbone - mixture of PMMA and PHEMAVarying water contentsAdditives such as UV blockers
3/30/2006 66
3/30/2006 67
3/30/2006 68
3/30/2006 69
3/30/2006 70
3/30/2006 71
3/30/2006 72
3/30/2006 73
Foldable IOL complications/explantations -
Survey Lens Totals2001
9%
8%
14%
16%28%
25%
Multifocal,SiliconeOne Piece (plate),SiliconeOne Piece with Haptics,AcrylicThree Piece,AcrylicThree Piece,HydrogelThree Piece,Silicone
3/30/2006 74
Reasons for Revision Surgery
Incorrect lens power seen most commonlyGlare/optical aberrationsDislocation/decentrationLate postoperative opacification
3/30/2006 75
IOL Optic Opacification
Surface opacificationOpacification within the substance of the opticAnalysis of opacifications reveals presence of calciumCalcium stainingScanning electron microscopic analysis
3/30/2006 76
3/30/2006 77
3/30/2006 78
3/30/2006 79
3/30/2006 80
3/30/2006 81
3/30/2006 82
3/30/2006 83
Total Total diameter: diameter: 9.7 mm9.7 mm
Accommodative IOL: 1CU (HumanOptics)