Hemodialysis

1. 10/30/2022 1
Hemodialysis
External procedure
 3 sessions of 4 hrs a week
 Filtration process only
Hollow Fiber Dialyzer
Blood flows in and is cleaned
using the process of diffusion
and ultrafiltration.

2. 10/30/2022 2
Biocompatibility in
Hemodialysis
 Significant interaction of blood
 Activation of humoral enzymatic pathways
 Activation of white blood cells and platelets
Cuprophane membranes
 Propose a biologically inspired design?

3. 10/30/2022 3
Annu. Rev. Med. 1997. 48:467–76
Copyright © 1997 by Annual Reviews Inc. All rights reserved
ACUTE RENAL FAILURE: Role of
Dialysis Membrane Biocompatibility
Manuel Pascual, MD, Rita D. Swinford, MD,1 and Nina Tolkoff-Rubin,
MD
The Renal Unit and Transplantation Unit and 1 Pediatric Nephrology
Division, Massachusetts General Hospital and Harvard Medical
School, Boston, Massachusetts 02114
Hemodialysis Membranes: Interleukins, Biocompatibility, and
Middle Molecules
WALTER H. HORL
Department of Medicine, Division of Nephrology, University of
Vienna, Vienna, Austria.
J Am Soc Nephrol 13: S62–S71, 2002

4. 10/30/2022 4
Hydrogels

5. 10/30/2022 5
Definition
-water insoluble, three dimensional network of polymeric
chains that are crosslinked by chemical or physical
bonding;
-polymers capable of swelling substantially in aqueous
conditions (eg hydrophilic)
-polymeric network in which water is dispersed throughout
the structure

6. 10/30/2022 6
The Cross-links may be physical
or chemical:
 by reaction of one or
more monomers with
pendant functional
groups
 hydrogen or ionic
bonding, or
 van der Waals
interactions
+
+
_
_
_
_
_
_

7. 10/30/2022 7
Hydrogels
 One or more highly electronegative atoms which results
in charge asymmetry favoring hydrogen bonding with
water;
 Because of their 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;

8. 10/30/2022 8
Hydrogels: Swelling
 Degree of swelling can be quantified by:
 ratio of sample volume in the swollen state to volume
in the dry state
 weight degree of swelling: ratio of the weight of
swollen sample to that of the dry sample

9. 10/30/2022 9
Hydrogels:
 In a chemically cross-linked hydrogel, all of the polymer
chains are connected by covalent bonds to form a
network; and, thus
 Can be viewed as one one molecule of large size or
supramacromolecules;
 The thermodynamically driven swelling force is
counterbalanced by the retractive force of the crosslinked
structure;
 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

10. 10/30/2022 10

11. 10/30/2022 11
Xerogels
 Dried 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;

12. 10/30/2022 12
Chitosan

13. 10/30/2022 13
Hydrogels: Swelling
 Why is the degree of swelling important?
 solute diffusion coefficient through the hydrogel
 surface properties and surface mobility
 optical properties (particularly for contact lens
applications)
 mechanical properties

14. 10/30/2022 14
Applications
Pharmaceutical applications
 monomer composition and relative amounts of multi-
polymer hydrogels can be varied to alter the diffusion
characteristic and
 permeability of the gel containing pharmaceutical agents
Methods for drug delivery
 drug gets trapped in the hydrogel during polymerization
 drug introduced during swelling in water
 Release occurs by outflow of drug from the gel and inflow
of water to the gel

15. 10/30/2022 15
Drug delivery

16. 10/30/2022 16
Examples of biological
hydrogels:
 Jello (a collagen gel ~ 97% water)
 Extracellular matrix components
 Polysaccharides
 DNA/RNA
 Blood clot
 Mucin - lining the stomach, bronchial tubes,
intestines
 Gycocalyx - lining epithelial cells of blood vessels
 Sinus secretions

17. 10/30/2022 17
Fibrin Hydrogel (Blood Clot)

18. 10/30/2022 18
Function of a biological hydrogel
 Decreased permeability to large molecules
 Structural strength (for epithelial cell walls)
 Capture and clearance of foreign substances
 Decreased resistance to sliding/gliding
 High internal viscosity (low washout)

19. 10/30/2022 19
Hydrogel Forming Polymers
O
HO
OH
HO2C
O
O
HO
NH
HO
O
O
O
HO
OH
NaO2C
O
O
O
O
NH
O
n
poly(hyaluronic acid) poly(sodium alginate)
n
n
poly(ethylene glycol)
n
poly(lactic acid)
n
poly(N-isopropyl acrylamide)
Natural
Synthetic

20. 10/30/2022 20
Hydrogels
Highly swollen hydrogels:
 cellulose derivatives
 poly(vinyl alcohol)
 poly(N-vinyl 2-pyrrolidone), PNVP
 poly(ethylene glycol)
Moderately or poorly swollen hydrogels:
 poly(hydroxyethyl methacrylate), PHEMA and derivatives
One may copolymerize a higly hydrophilic
monomer with other less hydrophilic monomers to achieve
desired swelling properties

21. 10/30/2022 21
Hylauronic Acid

22. 10/30/2022 22
Polyelectrolyte Hydrogels

23. 10/30/2022 23
Polyelectrolyte Multilayers
Layer by layer deposition

24. 10/30/2022 24
Alginate gels

25. 10/30/2022 25
Alginate gels

26. 10/30/2022 26
Enzyme Immobilization

27. 10/30/2022 27
Cell Encapsulation

28. 10/30/2022 28

29. 10/30/2022 29

30. 10/30/2022 30
Important features of hydrogels
 Usually comprised of highly polyionic polymers
 Often exhibit large volumetric changes eg. Highly
compressed in secretory vessicle and expand
rapidly and dramatically on release
 Can undergo volumetric phase transitions in
response to ionic concentrations (Ca++, H+),
temperature, ..
 Volume is determined by combination of attractive
and repulsive forces:
 repulsive electrostatic, hydrophobic
 attractive, hydrogen binding, cross-linking

31. 10/30/2022 31
Hydrogel Forming Polymers
O
HO
OH
HO2C
O
O
HO
NH
HO
O
O
O
HO
OH
NaO2C
O
O
O
O
NH
O
n
poly(hyaluronic acid) poly(sodium alginate)
n
n
poly(ethylene glycol)
n
poly(lactic acid)
n
poly(N-isopropyl acrylamide)
Natural
Synthetic

32. 10/30/2022 32
Poly(methyl methacrylate)

33. 10/30/2022 33
Acrylates

34. 10/30/2022 34
Methacrylates

35. 10/30/2022 35
How biological hydrogels grow
•Polymerization/deposition
(blood clots)

36. 10/30/2022 36
Preparation of Hydrogels
Hoffman, A. S. Adv. Drug Deliv. Rev., 2002, 43, 3

37. 10/30/2022 37
Applications in Biomaterials
and Tissue Engineering
 Cell Encapsulation
 Drug delivery
 Surface modification
 Enzyme Immobilization
 Biosensors
 Lab on a chip

38. 10/30/2022 38
Hydrogels: PHEMA
 The most widely used hydrogel
 water content similar to living tissues
 inert to biological processes
 shows resistance to degradation
 permeable to metabolites
 not absorbed by the body
 withstands sterilization by heat
 prepared in various shaped and forms

39. 10/30/2022 39
Hydrogels: Applications
 Biomedical use due to bio- and blood-compatibility
 Pharmaceutical use due to hydrophilicity (controlled/sustained
drug release)
 Earliest biomedical application contact lenses
 good mechanical stability
 favorable refractive index
 high oxygen permeability
 needs hygienic maintenance
 unable to correct for astigmatism
 lubricating surface coating
 used with catheters, drainage tubes and gloves
 non-toxic

40. 10/30/2022 40
Corning® Ultra Low Attachment Products
Unique hydrogel surface inhibits cell
attachment

41. 10/30/2022 41
Ocular Drug Delivery

42. 10/30/2022 42
Applications
 artificial tendon and cartilage
 wound healing dressings (Vigilon®, Hydron®,
 Gelperm®)
 non-antigenic, flexible wound cover
 permeable to water and metabolites
 low-strength
 artificial kidney membranes
 artificial skin
 maxillofacial and sexual organ reconstruction
materials
 vocal cord replacement

43. 10/30/2022 43
Applications
Pharmaceutical applications
 monomer composition and relative amounts of multi-
polymer hydrogels can be varied to alter the diffusion
characteristic and
 permeability of the gel containing pharmaceutical agents
Methods for drug delivery
 drug gets trapped in the hydrogel during polymerization
 drug introduced during swelling in water
 Release occurs by outflow of drug from the gel and inflow
of water to the gel

44. 10/30/2022 44

45. 10/30/2022 45

46. 10/30/2022 46
Contact lens
 PMMA
 HEMA
 Fabrication methods
 Computer assisted cutting (lathe)-PMMA rods
 Spin casting-polymerization
 Molding-polymerization

47. 10/30/2022 47

48. 10/30/2022 48

49. 10/30/2022 49

50. 10/30/2022 50

51. 10/30/2022 51

52. 10/30/2022 52

53. 10/30/2022 53

54. 10/30/2022 54