1. Medical Device Issues
Prof. David Woolfson

2. Medical Device
A device implanted permanently or temporarily in the body for a mechanical/structural purpose. Usually manufactured by extrusion or injection-moulding (polymeric devices)
Drug Delivery Device
A device intended to deliver a drug for prophylactic or therapeutic purposes. Usually, such devices control the rate at which the drug is made available to the body (controlled release devices
Hybrid device
A medical device with a primary mechanical/structural function and a secondary drug delivery function, either for device protection or targeted drug delivery.
Devices

3. Insertion pain & tissue trauma Haemocompatibility
Device-
related
problems
Insertion pain & tissue trauma
Haemocompatibility
Device encrustation - morbidity
Device-related Infection - mortality
>250,000 device-related infections/year in the UK cost >£100million due to longer hospitalisation and more aggressive treatment
There is now substantial interest in bioactive medical devices that encompass a drug delivery function

4. Foley
urinary
catheter

5. Surface formation of microbial biofilm, leading to UTI
Urinary catheterisation is frequently employed in clinical and domiciliary care of patients. Catheterisation may be short or long-term (indwelling, Foley-type) or intermittent (Nelaton-type)
Catheter blockage due to encrustation with complex inorganic salts, resulting in device failure due to obstruction of flow, remains a major problem in longer-term use, as does device-related infection
Tissue trauma due to insertion, and also upon removal, is a further problem with most types of catheterisation
Surface formation of microbial biofilm, leading to UTI
Catheter
issues

6. ET TUBES from ICU PATIENTS at (clockwise) 4h, 8h, 12h
Endo-
tracheal
tube

7. 24h 4h 48h 5d Biofilm formation Surface of endotracheal tube
retrieved from
an ICU patient
48h 5d 4h
24h

8. Ureteral stents from GORMAN SP et al BRITISH JOURNAL OF UROLOGY
73 (6):

9. Drug-Eluting Stents (stainless steel, nitinol)
Cardio-
vascular
stents
angioplasty balloon
mounted stent
stent in situ
Drug-Eluting Stents (stainless steel, nitinol)
The drug-eluting stent is basically a bare metal stent that is then coated with a slow-to-moderate-release drug formulation, sometimes embedded in a polymer. It is hoped that this will prevent or at least reduce restenosis, reclosure of the coronary artery, one of the biggest limitations of angioplasty and causes for repeat procedures

10. The rapid evolution of clinical medicine exerts a continuing demand on manufacturers
Manufacturers with a high cost base must add value to their lower-end products by making significant technological advances in order to compete with commodity suppliers, e.g. in continence care, respiratory, cardiovascular sectors
Real clinical improvements are needed to demonstrate cost-savings to healthcare systems and justify higher reimbursement costs for healthcare systems
Manufacturing and design improvements (e.g smooth device surface) not sufficient - bioactive devices ultimately required
Medical
Devices -
economics

11. [ ] Medical Devices - polymers poly(vinyl chloride) poly(styrene)
plasticised or unplasticised
poly(styrene)
crystalline or amorphous (tacticity)
poly(ethylene)
HDPE or LDPE
CH2 CH2 [ ] n
poly(urethane)
HDPE or LDPE
silicone repeat unit
crosslinked to form an elastomer

12. Device
coatings
Device coatings can add lubricity, biocompatibility, and antimicrobial action to device surfaces. Coatings can be used to release drugs or make implanted devices more visible to imaging systems
Many device coatings are hydrophilic polymer-based formulations, usually hydrogels
Enhanced device lubricity is one major reason for coating, e.g catheters and guidewires can be spray coated with a thin layer of polytetrafluoroethylene (PTFE)

13. Coatings may be applied to non-polymeric devices fabricated from stainless steel, platinum or nitinol (nickel titanium)
Drug delivery coatings that render a device ‘bioactive’ are now of major interest. Typically, a drug in a carrier hydrogel coating is released as the hydrogel imbibes water from surrounding biological fluids and swells
Coating technologies presently include dip-coating, spray-coating, co-extrusion and chemical grafting to polymers, whereby the drug is added to the coating mix pre-process
Relevant active agents include non-antibiotic antimicrobials, antibiotics and inorganic metallic elements such as silver
Bioactive
coatings

14. chemically controlled
release
mechanisms
reservoirs (membranes)
matrices (monoliths)
diffusion controlled
bioerosion/degradation
pendant chain
chemically controlled
osmotic pressure
swelling
solvent activated
externally ‘smart’ controlled
e.g. sensor-based

15. Matrix (monolithic) Reservoir Q Q √t t
Diffusion
controlled
systems
Matrix (monolithic)
drug uniformly distributed through polymer matrix
no danger of drug dumping
first-order kinetics Q √t Q t
drug core surrounded by non-biodegradable polymer
properties of drug and polymer govern diffusion rate
‘drug-dumping’ if membrane ruptures
zero-order kinetics from ‘constant activity’ source
Reservoir Q t

16. Effect of bioactive agents released from silicone Bioactive
biomaterials
Miconazole nitrate
Nalidixic acid
Gentamicin sulphate
Ampicillin 1 2 3 4 5 6 7
Miconazole nitrate
Nalidixic acid
Gentamicin sulphate
Ampicillin 10 15 20 25 30
Zone of Inhibition
(mm) 8
Time (days) of Repeated Microbial Challenge

17. Alteration of surface topologies (nano-engineering)
NewLEIF
opportunities
in bioactive
biomaterials
Alteration of surface topologies (nano-engineering)
Direct implantation on devices surfaces (polymeric, metallic) of inorganic elements with antimicrobial properties, e.g silver , without the need for coating
Surface implantation on preformed devices of organic compounds (MW < 500) with antimicrobial activity through generation of highly charged species
Laboratory and clinical assessments of efficacy