HOST RESPONSE

Question 1

What happens if biomaterials/scaffold are not compatible with cells? How have we learnt this?

Answer 1

• Inflammatory or immune response.

- Have learnt this from transplantation.

Question 2

What are the adverse effects of bio materials on the body?

Answer 2

Effects of biomaterial on the body - impacts wound healing, infection, toxicity, tumerogenicity, hypersensitivity reactions

Question 3

What are the effects of the body on a biomaterial?

Answer 3

Enzymatic degradation, calcification, abrasion and corrosion

Question 4

FOREIGN BODY RESPONSE - what causes this?

Answer 4

Injury to tissue by surgery

Causes injury to blood vessels

Question 5

Problem with foreign body response and using biomaterials ?

Answer 5

Cannot predict the body’s response to a particular material –> shells of collagen laid down in fibrous encapsulation is larger for some materials than others
Makes sense for body to isolate foreign material to prevent damage!

Question 6

Negative effects of fibrous encapsulation on tissue engineering devices?

Answer 6

• Implanted microelectrodes –> impacts transmission of electrical signals
• vascularisation
• can create a diffusion barrier to the device

Question 7

Infection - how common, different types?

Answer 7

Relatively common, bacterial communities grow on abiotic materials (eg STAPHYLOCOCCI). They are initially localised to the site of the implant and can spread.

Question 8

Importance of minimal FB response?

Answer 8

Minimal FB response = maximal integration of device. Increased integration = increased tissue flexibility

Question 9

What are bacterial biofilms?

Answer 9

Communities of bacteria grown on abiotic materials
Bacteria embed in a self made matrix.
Ancient adaptation.
Coordinated behaviour of bacteria = enhanced survival of population

Question 10

Stages of bacterial biofilm development

Answer 10

Attachment — Cell-cell adhesion — Proliferation — maturation. Bacteria disperse from the colony and feedback positively onto process!

Question 11

Relevance of mature biofilms? Strains of relevance?

Answer 11

Mature biofilms are extremely resistant to antibiotics.
Staphyloccoci are particularly prone to creating these films.
Multi drug resistant strains include MRSE/MRSA

Question 12

Examples of BIOFILM infections?

Answer 12

Infected surgical repair materials - staples, sutures and meshes
Orthopedic joint replacement infections -

Question 13

Why do orthopedic joint replacement infections tend to be more common than other infections from foreign materials

Answer 13

Difficult to detect and access
Hard to deliver high concentrations of antibiotics to treat these areas
MAY HAVE TO HAVE SECOND SURGERY TO REMOVE

Question 14

What is meant by ‘the race to the surface’

CONSIDER THIS IN EXAM QUESTION

Answer 14

Race between bacteria and cells to form layer on biomaterial surface
Dictates whether infection will appear or not –> bacteria need a place to adhere to material

Question 15

Non-fouling surfaces - What is meant by this? Example?

Answer 15

Surfaces which are resistant to adsorption of proteins and / or adhesion of cells
PEG POLYMERS ARE AN EXAMPLE OF THIS
May be useful in inhibiting bacterial colonisation

Question 16

How can you edit PEG polymers to prevent from being non-fouling?

Answer 16

ADD RGD DOMAIN! RGD domains are found on cells to allow integrins to act as receptors for other adhesion molecules.
Can decorate PEG polymer surfaces with RGD domains using MICROSTAMPING techniques.
This may inhbit bacterial colonisation in medical devices.

Question 17

How to RGD domains instruct mammalian cells to adhere but not bacterial?

Answer 17

Differentially instructive matrices (protein micronets) assemble into structures and instruct mammalian cells to adhere but not bacterial cells.

Question 18

What are the Systemic and remote effects of implanted devices? Example of this?

Answer 18

By-products of physical/chemical wear can enter the blood stream and cause side effects in other parts of the body
Example: metal-on-metal hip replacements; releasing cobalt and chromium in the blood

Question 19

what is meant by Thromboembolic complications?

Answer 19

Exposure of blood to an artificial material can cause thrombosis, embolization and consumption of platelets and plasma coagulation factors

Question 20

Stent thrombosis - what is it and what is it caused by?

Answer 20

A rare but serious complication
Clinical consequences: death (20-48% cases) or myocardial infarction (60-70% cases)
Clinical approach to controlling thrombosis is the use of anticoagulant drugs

Question 21

Tumours associated with implants? Pathology?

Answer 21

Orthopedic implant-related osteosarcomas are an example. Potential tumorogenicity of some biomaterials demonstrated in animal models
Neoplasms associated with therapeutic implants in humans are rare
Difficult to prove causal relationship in some cases
Mechanisms not clearly understood

Question 22

Cells and immune response –> humoral and cellular immunity?

Answer 22

Humoral immunity - soluble antibodies produced by B lymphocytes
Cellular immunity - mediated by T lymphocytes
On the whole, causes rejection of cells from the patient –> often seen in allogeneic strategies)

Question 23

MICROENCAPSULATION - how does it work?

Answer 23

Doesn’t supress immune cells (like in the edmonton protocol) but uses selectively permeable membranes meaning that cells can secrete the insulin required and also receive nutrients but membranes will not allow permeation of immune cells

Question 24

Other approaches for immunoisolation?

Answer 24

• G.E of cells to secrete neurotrophic and angiogenic factors
• Enhanced tumour specific cellular immunity