Lecture 11 - Hydrogels 2

Question 1

What does stiffness refer to in the context of hydrogels?

Answer 1

Stiffness refers to the viscoelastic behavior of the material, quantified as Young’s modulus, which measures how easily a material deforms in response to stress.

Question 2

What is Young’s modulus?

Answer 2

Young’s modulus is a measure of how easily a material deforms, defined as the ratio of stress to strain.

Question 3

What is the difference between macro/bulk stiffness and local stiffness in hydrogels?

Answer 3

Macro/bulk stiffness refers to the overall stiffness of the material as perceived by humans (rheology), while local stiffness refers to the stiffness at the fiber level, which is what a cell would ‘feel’.

Question 4

What techniques are used to assess local stiffness in hydrogels?

Answer 4

Microrheology and Atomic Force Microscopy (AFM) are used to assess local stiffness.

Question 5

What are the key components of the extracellular matrix (ECM) to consider when creating implantable biomaterials?

Answer 5

Key components include:
* Non-toxicity
* Mechanical stability and controlled degradation
* Provide chemical and physical cues to cells
* Support and guidance for cells
* Promotion of healing and tissue reconstruction
* Integration with native tissue
* Promotion of functionality

Mimicking depends on the application; repair, reconstruction, device protection

Question 6

What are the considerations for implanting materials into the body?

Answer 6

Considerations include the immune response, repair pathways, and chronic inflammation.

Question 7

What is the immune response to implantable materials?

Answer 7

The immune response may involve repair pathways or chronic inflammation, depending on the material and the body’s reaction.

Question 8

What are the types of immune cells involved in the response to foreign materials?

Answer 8

Key immune cells include:
* Neutrophils
* Monocytes
* Macrophages
* Foreign body giant cells
* Fibroblasts
* B cells
* T cells
* Natural killer cells
* Mast cells
* Dendritic cells

Question 9

What is the role of neutrophils in the immune response?

Answer 9

Neutrophils are the first responders that flood the site of foreign material or infection to break down foreign matter.

Question 10

What is the function of monocytes in the immune response?

Answer 10

Monocytes are precursors of macrophages that help regulate the immune response and contribute to the breakdown of foreign matter.

Question 11

What are macrophages, and how do they function in the immune response?

Answer 11

Macrophages are attracted by precursor cells and can switch forms between M1-inflammatory and M2-anti-inflammatory, playing a critical role in the immune response.

Question 12

What are foreign body giant cells?

Answer 12

Foreign body giant cells are formed from the collection of macrophages to attack persistent foreign materials.

Question 13

What role do fibroblasts play in the immune response?

Answer 13

Fibroblasts recruit immune cells and produce a collagen-rich matrix, contributing to fibrosis.

Question 14

Fill in the blank: The immune response to implantable materials can lead to _______ or chronic inflammation.

Answer 14

repair pathways

Question 15

True or False: The stiffness of synthetic hydrogels is not important when using them in cell-related applications.

Answer 15

False

Question 16

What factors influence the stiffness of hydrogels?

Answer 16

Factors include the arrangement of fibers, which can be controlled by driving them closer together or further apart.

Question 17

What is microrheology?

Answer 17

Microrheology is a technique used to study the mechanical properties of materials at the microscale, particularly useful for assessing local stiffness.

Question 18

What are the implications of the immune response for the design of biomaterials?

Answer 18

Biomaterials must be designed to minimize adverse immune reactions while promoting healing and integration with native tissues.

Question 19

What is immunomodulation?

Answer 19

Changing the body’s immune response, for example through immunosuppressant drugs, small molecules, and biologics.

Question 20

What is a necessary aspect of the immune response for repair for biomaterials?

Answer 20

Working with a response; does not involve ‘no immune response’ as this is necessary for repair.

Question 21

What should be avoided to prevent chronic inflammatory response?

Answer 21

Repeated cycles of inflammatory cells flooding the area and preventing fibrosis.

Question 22

What type of materials contribute to an M2 macrophage response?

Answer 22

Non-toxic materials and material components (anti-inflammatory)

Question 23

What characterises the M2 phenotype?

Answer 23

Release of anti-inflammatory cytokines, e.g., IL-10 and TGF-β, matrix reorganization, and debris clearance.

Question 24

What is biomimicry in the context of immunomodulation?

Answer 24

Replicating the existing healthy internal environment.

Question 25

What is the aim of the macrophage response in tissue repair?

Answer 25

Achieve the M2 phenotype.

Question 26

What was the experimental model used to study the macrophage response?

Answer 26

Rat partial-thickness abdominal muscle.

Question 27

What was observed at the interface after 28 days in the experiment?

Answer 27

Increased infiltration of mononuclear cells.

Question 28

What were the findings regarding gel encapsulation and giant cells in the experiment?

Answer 28

No evidence of gel encapsulation, multinucleate giant cells, or foreign body reaction.

Question 29

What markers were found to be higher in the M2 phenotype compared to M1?

Answer 29

M2 markers.

Question 30

What is the significance of new ECM and neovascularization in tissue integration?

Answer 30

Indicates early myogenic differentiation towards muscle fibers.

Question 31

What are Shape Memory Alloys (SMAs)? ## Footnote Non-peptide systems

Answer 31

Materials that change their shape in response to temperature, e.g., Nitinol.

Question 32

What application do piezoelectric materials have? ## Footnote Non-peptide systems

Answer 32

Generate electrical charge in response to mechanical stress, used in sensors and devices.

Question 33

What are conductive polymers used for? ## Footnote Non-peptide systems

Answer 33

Conduct electricity and interact with the nervous system, e.g., PEDOT.

Question 34

What are bioactive ceramics used for? ## Footnote Non-peptide systems

Answer 34

Used for bone implants and can promote healing or growth.

Question 35

What advantage do hSAF peptide-based hydrogels offer?

Answer 35

Access to a range of tissue-like stiffnesses.

Question 36

What is the goal of creating non-degradable protective envelopes?

Answer 36

Protect function and integrate with surrounding tissue. ## Footnote E.g. to wrap around hard devices.

Question 37

What components of the ECM are prioritized in creating materials to avoid chronic inflammatory response?

Answer 37

Specific ECM components that facilitate healing.

Question 38

What is a good starting point for research on immunomodulatory systems?

Answer 38

The peptide hydrogel case.

Question 39

What is step 1 in immune response after implantation?

Answer 39

Protein adsoprtion (minutes)

Question 40

What is step 2 in immune response after implantation?

Answer 40

Acute inflammation (hours/days) * Neutrophils are first responders and signal to other cells * Monocytes with neutrophils decide if it will be adsorbed

Question 41

What is step 3 in immune response after inplantation?

Answer 41

Chronic inflammation (weeks) * If problem is too big, macrophages try to break materials into small parts * If cannot be broken down, macrophages adopt foreign giant body cell form * Body can get stuck within cycle

Question 42

What is step 4 in immune response after implantation?

Answer 42

Collagen encapsulation (months) * Fibroblasts flood area and produce fibrin (exists in ECM) * Start to knit capsule and isolate from rest of body creating a fibroid

Question 43

What are the applications of anti-FBR?

Answer 43

* As fillers (artificial vitreous) * As coatings (sensor coatings) * As vehicles (cell encapsulations)

Question 44

Route 1 of immunomodulation

Answer 44

1) Conjugated molecules with desired biological property onto biomaterials, e.g. heparin-functionalised polymer micelles feature anti-thrombogenic property

Question 45

Route 2 of immunomodulation

Answer 45

2) Molecules from phylogenetically distant organisms, e.g. certain molecules from arthropods and mollusk will likely trigger response in humans

Question 46

Route 3 of immunomodulation

Answer 46

3) Design high molecular weight biomaterials, high MW materials likely crosslink B-lymphocytes inducing an immune response

Question 47

Route 4 of immunomodulation

Answer 47

4) Design chemically heterogenous macromolecules, heteropolymers are more immunogenic

Question 48

Route 5 of immunomodulation

Answer 48

5) Control physiochemical and morhphological properties of biomaterials, e.g. surface charge, dimensionality, hydrophobicity, shape changes impart immunogenicity

Question 49

Peptide case study of hSAF ## Footnote Replication of the chemical and physical environment

Answer 49

hSAF p1 and hSAF p2 undergo gel formation (self-assembling hydrogel)

Question 50

What is the implantable soft robot technology?

Answer 50

Aims to deploy engineered robotic artificial musclular assistance inside the body to: * Restore stength and control in mobility * Restore controllable muscular capabilities for suffers of trauma, stroke, incontinence, and degenerative diseases

Question 51

Example of hydrogel used for drug delivery

Answer 51

Jin et al. 2018, introduced a melittin-RADA32 hybrid hydrogel loaded with doxorubicin for effective chemoimmunotherapy against B16-F10 tumor-bearing mice by the activation of immunosuppressive tumor microenvironments