-
||
08.10.2019Jack Kendall
10/8/2019Jack Kendall 1
Paper 1 – Particle Hydrogels on Hyaluronic acid building blocksMaterials and Mechanics in Medicine HS 2019
-
||
15.15-15.30: Paper Overview
15.30-16.00: Solve the Quiz (optional)
10/8/2019 2
Today
Jack Kendall
-
|| 10/8/2019 3
Paper 1
Jack Kendall
-
||
Linear, non sulfated GAGs Natural ECM component biodegradable, non-immunogeneic Multiple sites for modification:
Carboxyl and hydroxyl groups
10/8/2019 4
Hyaluronic Acid (HA) = Hyaluronan
Jack Kendall
PresenterPresentation NotesBackground informations1)An unbranched polysaccharid2)One of the most important components of the ECM Can be naturally metabolized and cleared in the body without producing toxic degradation products3)It can form a hydrogel under mild conditions e.g. chemical modification, crosslinking or photo-crosslinking
GAGs= GlycosaminoglycanGlucoronic acid=uronic acid
-
||
Hydrophilic crosslinked polymers Natural/synthetic polymeric building blocks For example: Hyaluronic acid, Chitasan, Alginate, PEG,…
10/8/2019 5
Hydrogels
Jack Kendall
PresenterPresentation NotesBackground informationIn the paper: Hyaluronic acid used as building blocks
hydrogels can be chemical OR physical:Chemical: Crosslinking occurs by covalent bondingPhysical: Crosslinking is given by weaker forces e.g. hydrogen bonds, hydrophobic interactions or electrostatic forces.
-
||
Mimic ECM 3D structural framework Moldable Tunable mechanical properties Water-based Swollen mesh (mesh size: 10-100nm)
Degradation is required for cellular infiltration.
Why?
10/8/2019 6
Why polymeric hydrogels?
Jack Kendall
PresenterPresentation NotesFor example: By incorporation of chemical and physical bioactive cuesIn which cells grow and secrete ECM.Can take the form of any mold before complete gelation (sol-gel transition)4) For example: elastic, viscoelastic, stress relaxing. It depends on the chosen chemistry5) Keep wounds hydrated and protected from bacterial infectionsBecause: Cells are in micrometers in size (Cells are bigger than the mesh sizes Cells can’t go through)
-
||
How to modulate it?a) Integration of degradation sitesb) Noncovalent bonds Stress relaxing
Challenge: Too slow degradation no cell infiltration, fibrotic
encapsulation Too fast degradation no mechanical support
Need for balance between degradability and long-term mechanical support
10/8/2019 7
Degradation rate
Jack Kendall
PresenterPresentation NotesHOW to modulate (The 2 methods presented in the paper)a) For example: hydrolysable bonds, protease degradable peptides allow cellular infiltrationb) Noncovalent bondsallow material to stress relaxingallow cellular infiltrationAllow cellular infiltration
Ideally, a scaffold should be biodegradable at a rate that matches with the anabolic activity of the cells to create space for new tissue.
-
|| 10/8/2019 8
Why is cellular infiltration essential?
Jack Kendall
-
|| 10/8/2019 9
Why is cellular infiltration essential?
To allow endogeneous tissue integration
Jack Kendall
PresenterPresentation NotesCells will produce ECM to take over the structural role of the scaffold, which will degrade over time.
-
|| 10/8/2019 10
Hydrogel (Paper)
Jack Kendall
PresenterPresentation Notesporous scaffold from voids between the packed beads.Advantage of standard bulk hydrogel: No harsh chemical methods which limit bioactive signal incorportation and injectability
-
|| 10/8/2019 11
Methods to produce microporous scaffolds
Salt leaching Gas foaming Lyophilization Sphere templating
Jack Kendall
PresenterPresentation Notes4 commonly emploiyed methods for producting microporous scaffolds
-
|| 10/8/2019 12
Salt leaching
Jack Kendall
PresenterPresentation Notes 1)Salt crystals such as NaCl (common table salt) are put into a mold and polymer is poured over the salt, penetrating into all the small spaces left between the salt crystals.2) The polymer is hardened and then the salt is removed by dissolving it in a solvent e.g. water or alcoholOpen holes/pores where the salt once wasThe pore size can be altered by simply changing the porogen size
-
|| 10/8/2019 13
Gas foaming
Jack Kendall
PresenterPresentation Notes(b): Gas foaming: Used the nucleation and growth of gas bubbles dispersed throughout a polymer to generate a porous structure.
-
|| 10/8/2019 14
Lyophilization (=Freeze drying)
Jack Kendall
PresenterPresentation NotesWorks by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate
(a low temperature dehydration process that involves freezing the product, lowering pressure, then removing the ice by sublimation)
-
|| 10/8/2019 15
Sphere templating
Jack Kendall
PresenterPresentation NotesAll pores with the same sizeAll pores interconnected in 3 dimensions
-
||
Deeper characterization of HA MAP gels Generation of particle hydrogels using 3 different
annealing approaches Demonstrate the versality of those 3 approaches by
exploration of physical differences: Pores connectivity Pore area/void fraction Mechanical properties of the scaffold Cell spreading
10/8/2019 16
Aim (Paper)
Jack Kendall
-
||
Enzymatic reaction FXIIIa
Light-based radical polymerization Eosin Y
Amine/carboxylic acid-based cross-linking PEG-NHSAll three leads to the formation of a stable 3D scaffold
10/8/2019 17
3 Orthogonal annealing chemistries
Jack Kendall
-
||
FXIIIa A coagulation factor
10/8/2019 18
Enzymatic reaction
Jack Kendall
PresenterPresentation NotesA new approach in hydrogel formationEnzymes can be used to cleave or establish a chemical bond with greater efficiency than other methodsShort reaction times and specificityEnzyme-substrate specificityAvoids undesired or toxic side reactions.
-
|| 10/8/2019 19
Light-based radical polymerization(Eosin Y)
Eosin
Jack Kendall
PresenterPresentation NotesEosin. Most common staining method in histology; H&E= Hematoxylin and Eosin
-
||
PEG-NHS
PEG NHS
10/8/2019 20
Amine/carboxylic acid-based cross-linking
Jack Kendall
PresenterPresentation NotesCross-linking via amide bond
-
||
In HA based MAP Hydrogel:
Pore sizes are smaller than in other scaffolds Annealing of the beads is required Pore diameter depends on the packing density Cells loading during scaffold formation is possible Pores are interconnected HDFs cells spread in HA within 2 days
10/8/2019 21
Key Findings (Paper)
Jack Kendall
PresenterPresentation Notesa)
-
|| 10/8/2019 22
References and further reading
https://parjournal.net/article/view/2342
https://pubs.rsc.org/en/content/articlehtml/2013/cs/c3cs60040h
https://www.sciencedirect.com/science/article/pii/S1742706119304003
https://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.5b00671
https://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-
hydrogels/in-situ-forming-cross-linking-hydrogel-systems-chemistry-and-biomedical-
applications
Jack Kendall
https://parjournal.net/article/view/2342https://pubs.rsc.org/en/content/articlehtml/2013/cs/c3cs60040hhttps://www.sciencedirect.com/science/article/pii/S1742706119304003https://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.5b00671https://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-hydrogels/in-situ-forming-cross-linking-hydrogel-systems-chemistry-and-biomedical-applications
-
|| 10/8/2019 23
Quiz
Jack Kendall
Slide Number 1Slide Number 2Slide Number 3Slide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Slide Number 22Slide Number 23