14. Application of Bioengineered Products in Chronic Wounds Flashcards
What is a chronic wound?
A wound that fails to show any significant healing within 1 month despite optimum wound care
What are some disease causes of chronic wounds?
Lower Limb
- Venous leg ulcer
- Arterial Leg Ulcer
- Diabetic Foot ulcers
Other
- Pressure ulcers/sores
What are arterial leg ulcers caused by?
Arterial obstruction (atherosclerosis)
Reduced tissue oxygenation
Tissue necrosis
Whats the cause of diabetic foot ulcers?
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
What causes pressure ulcers?
Increase pressure and shear on tissues over bony prominences
- Decreased blood flow = ischaemic necrosis
- Tissue deformation
What exacerbated pressure ulcers?
Immobility Loss of sensation Tissue padding Excess moisture Increased age
What causes venous leg ulcers?
Reduced venous return due to
- Abnormalities of veins/valves
- Secondary abnormalities - deep vein thrombosis
Increased venous pressure - oedema
Minor trauma then = chronic wound
How are arterial leg ulcers treated?
Cessation of smoking
Cholesterol reduction
By-pass surgery
How are diabetic foot ulcers treated?
Control of diabetes
Pressure relief
By-pass surgery
How are venous leg ulcers treated?
Compression therapy, bandages, stockings etc
After treatment of underlying disease, how are chronic wounds treated?
Wound cleansing, debridement, dressings
What are the requirements for bioengineered products in chronic wounds?
Safety
Clinical effectiveness
- Randomized controlled trials
Cost effectiveness
What are the 3 main bioengineered products for chronic wounds?
Tissue scaffolds +/- cells Cells only +- support surface - secrete growth factors, cytokines and ECM Recombinant growth factors - Stimulate cell migration and prolif
What characteristics do tissue scaffolds posses?
Physical and mechanical characteristics
Surface chemistry + nano/microstructures
What are two main types of tissue scaffold products?
Bilaminated skin substitutes (dermis + epidermis)
- Apligraf - contains cells
- Integra - no cells
Dermis only
- Dermagraft
- Oasis
What is an example of a cell only product?
Epidermis only, (autologous keratinocytes)
- e.g. ReCell
What is an example of recombinant growth factor treatment/product?
Regranex - PDGF - platelet derived growth factor
What does the bilaminated skin substitue Apligraf consist of?
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
What is the cost of apligraf?
$1664 per 44cm2
5k per leg ulcer
What does the single dermis layer tissue scaffold dermagraft consist of?
Cryopreserved human fibroblasts on a bioabsorbable polyglactin mesh
Treatment of diabetic foot ulcers
Applied weekly
What is the cost of dermagraft?
$800 per 5cm x 7.5cm piece
What does the single dermis layer tissue scaffold, Oasis consist of?
Native collagen, elastin, glycosaminoglycans, glycoproteins and proteoglycans
Studied on venous leg ulcers
What is the average cost per ulcer of oasis?
$630, reasonable price
What are the limitations of substitutes containing living cells in chronic wounds?
Short - term activity due to short term life of cells
Limited evidence that products directly turn on resident cells
Repeated applications needed
Logistics
Expense
What is the cost of the cell based treatment ReCell?
$500
What is ReCell and how does it work?
Epidermal cells harvested from biopsy
No need for specialist
Available within 30 minutes
Sprayed or dripped as a suspension
up to 320cm2
Who is using ReCell treatment and what has their success been like?
Healthpoint Biotherapeutics
Use keratinocytes and fibroblasts
Treat venous leg ulcers
Apply fibrinogen
Growth arrested keratinocytes and dermal fibroblasts
Weekly application
How does the recombinant growth factor treatment, Regranex work?
FDA approved
Recombinant PDGF
10- 15% Improvement in diabetic foot ulcers
What is Vitrogro and how does it work?
Growth factors bind to ECM protein Vitronectin either directly or via intermediate binding proteins
Entire complex = VitroGro
What are the clinical considerations for bioengineered products?
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?
What are some ethical concerns associated with bioengineered products?
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
Does disease process influence success of bioengineered product?
Yes
Product may be affected by underlying disease
- Could be short term
- Wound recurrence common
What is the trifecta influencing patient response to bioengineered response?
Underlying disease pathophysiology
Host wound healing response
Bioengineered wound healing product
