14. Application of Bioengineered Products in Chronic Wounds

Question 1

What is a chronic wound?

Answer 1

A wound that fails to show any significant healing within 1 month despite optimum wound care

Question 2

What are some disease causes of chronic wounds?

Answer 2

Lower Limb

• Venous leg ulcer
• Arterial Leg Ulcer
• Diabetic Foot ulcers

Other
- Pressure ulcers/sores

Question 3

What are arterial leg ulcers caused by?

Answer 3

Arterial obstruction (atherosclerosis)
Reduced tissue oxygenation
Tissue necrosis

Question 4

Whats the cause of diabetic foot ulcers?

Answer 4

Peripheral vascular disease = impaired blood flow

Peripheral neuropathy = (cant feel stuff so you hurt feets) tissue trauma

Elevated glucose = glycosylation of proteins/lipids - altered activity

Question 5

What causes pressure ulcers?

Answer 5

Increase pressure and shear on tissues over bony prominences

• Decreased blood flow = ischaemic necrosis
• Tissue deformation

Question 6

What exacerbated pressure ulcers?

Answer 6

Immobility
Loss of sensation
Tissue padding
Excess moisture
Increased age

Question 7

What causes venous leg ulcers?

Answer 7

Reduced venous return due to

• Abnormalities of veins/valves
• Secondary abnormalities - deep vein thrombosis

Increased venous pressure - oedema
Minor trauma then = chronic wound

Question 8

How are arterial leg ulcers treated?

Answer 8

Cessation of smoking
Cholesterol reduction
By-pass surgery

Question 9

How are diabetic foot ulcers treated?

Answer 9

Control of diabetes
Pressure relief
By-pass surgery

Question 10

How are venous leg ulcers treated?

Answer 10

Compression therapy, bandages, stockings etc

Question 11

After treatment of underlying disease, how are chronic wounds treated?

Answer 11

Wound cleansing, debridement, dressings

Question 12

What are the requirements for bioengineered products in chronic wounds?

Answer 12

Safety
Clinical effectiveness
- Randomized controlled trials
Cost effectiveness

Question 13

What are the 3 main bioengineered products for chronic wounds?

Answer 13

Tissue scaffolds +/- cells
Cells only +- support surface
   - secrete growth factors, cytokines and ECM
Recombinant growth factors
  - Stimulate cell migration and prolif

Question 14

What characteristics do tissue scaffolds posses?

Answer 14

Physical and mechanical characteristics

Surface chemistry + nano/microstructures

Question 15

What are two main types of tissue scaffold products?

Answer 15

Bilaminated skin substitutes (dermis + epidermis)

• Apligraf - contains cells
• Integra - no cells

Dermis only

• Dermagraft
• Oasis

Question 16

What is an example of a cell only product?

Answer 16

Epidermis only, (autologous keratinocytes)

- e.g. ReCell

Question 17

What is an example of recombinant growth factor treatment/product?

Answer 17

Regranex - PDGF - platelet derived growth factor

Question 18

What does the bilaminated skin substitue Apligraf consist of?

Answer 18

Dermis = bovine Type 1 collagen + human fibroblasts
Epidermis = Human Keratinocytes

Can be applied as an out-patient - under compression therapy

Studies on venous leg ulcers

Question 19

What is the cost of apligraf?

Answer 19

$1664 per 44cm2

5k per leg ulcer

Question 20

What does the single dermis layer tissue scaffold dermagraft consist of?

Answer 20

Cryopreserved human fibroblasts on a bioabsorbable polyglactin mesh

Treatment of diabetic foot ulcers

Applied weekly

Question 21

What is the cost of dermagraft?

Answer 21

$800 per 5cm x 7.5cm piece

Question 22

What does the single dermis layer tissue scaffold, Oasis consist of?

Answer 22

Native collagen, elastin, glycosaminoglycans, glycoproteins and proteoglycans

Studied on venous leg ulcers

Question 23

What is the average cost per ulcer of oasis?

Answer 23

$630, reasonable price

Question 24

What are the limitations of substitutes containing living cells in chronic wounds?

Answer 24

Short - term activity due to short term life of cells

Limited evidence that products directly turn on resident cells

Repeated applications needed

Logistics

Expense

Question 25

What is the cost of the cell based treatment ReCell?

Answer 25

$500

Question 26

What is ReCell and how does it work?

Answer 26

Epidermal cells harvested from biopsy No need for specialist Available within 30 minutes Sprayed or dripped as a suspension up to 320cm2

Question 27

Who is using ReCell treatment and what has their success been like?

Answer 27

Healthpoint Biotherapeutics Use keratinocytes and fibroblasts Treat venous leg ulcers Apply fibrinogen Growth arrested keratinocytes and dermal fibroblasts Weekly application

Question 28

How does the recombinant growth factor treatment, Regranex work?

Answer 28

FDA approved Recombinant PDGF 10- 15% Improvement in diabetic foot ulcers

Question 29

What is Vitrogro and how does it work?

Answer 29

Growth factors bind to ECM protein Vitronectin either directly or via intermediate binding proteins Entire complex = VitroGro

Question 30

What are the clinical considerations for bioengineered products?

Answer 30

Is healing improved when combined with different care/treatment types? Which patients should be targeted? How is it used? Logistics? - Transport, shelf life etc Is there any impact on wound recurrence? Is it cost effective?

Question 31

What are some ethical concerns associated with bioengineered products?

Answer 31

Donor organs/cells raise concerns for ethnic or religious groups Healthcare professionals must ensure they are aware of the constituents of the products to gain patient consent

Question 32

Does disease process influence success of bioengineered product?

Answer 32

Yes Product may be affected by underlying disease - Could be short term - Wound recurrence common

Question 33

What is the trifecta influencing patient response to bioengineered response?

Answer 33

Underlying disease pathophysiology Host wound healing response Bioengineered wound healing product