Hydrogels

soft contact lenses, diapers,

wound dressings, cell culture and
drug delivery systems.

 Hydrogels are water-swollen, cross linked polymeric

structures containing either covalent bonds, physical crosslinks from H-bonds, entanglement.
Structural changes with salt, concentration, pH and
temperature
Hydrophilic
Ionic
Based upon method of preparation
Homo polymer hydrogels
Copolymer hydrogels (one must be hydrophilic)
Multi polymer hydrogels (.)
Interpenetrating Polymer hydrogels (first network swollen
in a monomer, reacts to form a second intermeshing
structure)

Interpenetrating polymers/ hydrogels

Mechanical properties
Application (drug delivery)
Activation pathways

Hydrogels (Charge)
(1) neutral hydrogels (wound dressings)
(2) anionic hydrogels (wound dressings)
(3) cationic hydrogels (drug delivery) (cationic network of crosslinked poly(ethylene oxide) (PEO) and polyethyleneimine (PEI))
(4) ampholytic hydrogels (targeted drug delivery)
(copolymerizing acrylamide with specialty monomers:
zwitterionic monomers N-(3-sulfopropyl)-Nmethacrylamidopropyl-N-dimethylammonium betaine (SB1)
and N-(3-sulfopropyl)-N-methacroyloxyethyl-N,Ndimethylammonium betaine (SB2) were both, in turn,
copolymerized with acrylamide to form ampholytic hydrogels.

Hydrogels (Physical Structure/Features)

(1) amorphous hydrogels

(2) semi crystalline hydrogels
(3) Hydrogen bonded hydrogels/ complexation structures

Hydrogels and their structure

(A) Ideal macromolecular network of a hydrogel

(B) Network with multifunctional junctions
(C) Physical entanglement
(D) Unreacted functionality
(E) Chain loops

Preparation
Chemical Crosslinking- direct reaction of a linear or
branched polymer with at least one difunctional small
molecular weight, crosslinking agent. Agent links 2 longer
MW chains through its di- or multi-functional groups.
Co-polymerization crosslinking reaction between one or
more abundant monomers and one multifunctional
monomer that is present in small quantities.
Photo-polymerization, Irradiative crosslinking- Monomer
and linear polymeric chains that are cross-linked by
means of an interlinking agent (eg. UV light, X-ray,
electron beams, Gamma)

Preparation
Photo-polymerization, Irradiative crosslinking- Monomer
and linear polymeric chains that are crosslinked by means
of an interlinking agent (eg. UV light, X-ray, electron
beams, Gamma)

Joddar et al. Biomaterials 2013

Swelling behavior
One of 2 possible processes of swelling- A dry hydrophilic
crosslinked network is placed in water. Macromolecular
chains interact with the solvent molecules. Network
expands to solvated state.

Swelling behavior

Swelling behavior

Swelling behavior
Highly swollen hydrogels: cellulose derivatives, PVA,
PNVP, PEG
Moderately and poorly swollen hydrogels PHEMA
Importance of equations
(i) the solute diffusion coefficient through these hydrogels
(ii) the surface properties and surface mobility
(iii) the optical properties (contact lens)
(iv) mechanical properties

Post implantation fate

Adsorption (proteinaceous components)
Absorption (soluble components such as water, ions,
proteins and lipids)
Cellular elements adhere to the surface- initiate their
chemical processes
Hydrolysis or oxidation post implant retrieval

Hydrolytic Biodegradation
Hydrolysis is the scission of susceptible molecular functional groups
by reaction with water ( chemical structure)
Hydrolysable polymers: carbonyls (O, N, S); eg: Amides, urethanes,
carbonates and anhydrides.

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Resorbable devices: drug delivery (extended release gels)

Hydrolytic Biodegradation-resistance

Hydrophobic backbone, or a highly crystalline morphologic structure

Hydrophobic moieties: hydrocarbon or fluorocarbon
Crosslinking, stereochemistry
High crystallinity (remember: isotactic, syndiotactic)
polypropylene
Thermal annealing
Compactness in shape/ porosity
Long Chain is beneficial? UHMWPE

Host-induced hydrolysis

Homeostasis (highly controlled reaction medium)

Isothermal (37C), neutral pH (7.4), aseptic, aqueous
Aggressive to an implant (adhesion, chemical reaction)
Hydrolysis: initiated by water (PGA-significant rate)
Ion-catalyzed hydrolysis: extracellular fluids H+, OH-, Na+, Cl-, HCO3-, PO43-,
K+, Mg2+
Very hydrophobic polymers (<2% water of saturation) absorb negligible
concentration of ions
Hydrogels (>15% by weight) are sieves for ion absorption- hydrolysis prone
Localized pH- acute inflammation, infection- catalyze rate of hydrolysis
Organic components such as lipoproteins (cation transporters)
Phagocytosis mechanisms: proteases, esterases, lipases (cell derived
proteins which act as catalysts for the scission of water labile functional
groups)
Synthetic polymers are also susceptible to hydrolysis: Polyesters, polyamides
Implanted devices which are in motion relative to neighboring tissue can
provoke inflammation, stimulating enzyme release (eg?)

Hydrolysis: Preclinical and Clinical

Experience
Polyesters
Poly(ethylene terephthalate) (PET) CV devices- sutures, arterial patches

Strong flexible polymer, highly crystalline, biostable

Breakage of fibers and device dilation
In vivo data: 30 7 yr (50% loss of fiber
strength in 10 2 yr)
With infection: pH 4.8 (humans and dogs)
Infection on polymers

Oxidative Biodegradation-polymer
structures

Direct oxidation by host

Host generated molecular species effect or
potentiate oxidative processes directly on the
polymer
Activated phagocytic cells responding to the injury
and foreign body response
Neutrophils- first line of attack (first few days)
Activated Macrophages (following few days)
Fusion products from macrophages (months to
years)
Oxygen is metabolized to form superoxide anion
(O2-.)
Superoxide dismutase (SOD) converts superoxide
to hydrogen peroxide- in the presence of (MPO)
converted to HOCl (potent oxidant)
HOCl can oxidize amine to chloramines (long lived
oxidants)
Also oxidize amides, ureas, urethanes-cleaving
these groups

Direct oxidation by host

Stress Cracking
Poly(ether urethane) elastomers
Surface attack of the polymer and by chemical changes induced by
relatively specific in vivo or in vitro oxidizing conditions
Eg:
1) Components contained residual processing and/or applied
mechanical stress /strain
2) Components were exposed to a medium of viable cellular and
extracellular body constituents
3) Polymers had oxidative susceptible groups
4) Failure analysis of implants revealed surface oxidation products
Connectors, insulators, for pacemakers and neurological simulators

How to control Stress Cracking?

Reduce Residual Stress, isolate polymer from cell contact.
Protect the polymer from stress cracking media.
Resistant polymers
Antioxidants (Vitamin E)

Stress Cracking

Stress Cracking

Stress Cracking

Stress Cracking

Device or environment mediated oxidation-Metal Ioninduced

Initiates on the enclosed inner surfaces of pacing lead insulation near
corroded metallic components and their entrapped corrosion
products
Smooth crack walls and random cracks (brittle fracture)

Device or environment mediated oxidation-Metal Ion-induced

Initiates on the enclosed inner surfaces of pacing lead insulation near

corroded metallic components and their entrapped corrosion
products
Smooth crack walls and random cracks (brittle fracture)

Device or environment mediated oxidation-Metal Ion-induced

Device or environment mediated oxidation-Metal Ion-induced

The metal ion-induced oxidation process involves corrosion of metallic

elements to their ions and subsequent oxidation of the polymer.
In operating devices, the metal ion may be formed by solvation, galvanic or
electrolytic corrosion, or chemical or biochemical oxidation

Device or environment mediated oxidation-Metal Ioninduced

In turn these metal ions develop oxidation potentials that may well be
enhanced in body fluids
As strong oxidants, they produce intermediates or attack the polymer to initiate
the chain reaction
Result of a highly complex interaction of the device: polymer and the body

External environment mediated oxidation

Electromagnetic radiation can affect integrity of the polymers:

Intraocular lenses: UV radiation
Maxillofacial components are vulnerable to sun light (UV)
Photo-oxidation
Antioxidants,
UV absorbers