Outline. Device Design. Introduction. Introduction. Introduction Medical Devices. Summary

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1 Outline Device Design Andrew Mikhail, Ghazaleh Farid Modjtahedi, Joanna Chong, Mike Shleiffer Introduction Medical Devices The artificial kidney Laser systems for eye surgery Drug delivery devices Synthetic blood vessels Summary Introduction Introduction What is a medical device? An apparatus that aids in diagnostic or therapeutic medical procedures Medical device sector covers more than 8000 types of products Includes: bandages, surgical tools, imaging (MRI, CT etc), implantable devices, ventilators, etc. Why are they important? Improve health care (New treatments, early diagnosis) Reduce cost of health care Improve safety In the news: Ultrafast laser detection of cancer cells also may improve understanding of stem cells Smart nanocarrier technology for use in cancer treatment Patients can now swallow pill-sized, disposable cameras to help diagnose diseases of the esophagus MicroJet injector for painless injections New computer mouse adapter that enables people who suffer from hand tremors to eliminate excessive cursor movement Diverse area of research with endless possibilities! Headlines from News-Medical.Net 1

2 Selected topics Introduction 1) The artificial kidney 2) Laser systems for eye surgery 3) Drug delivery devices 4) Synthetic blood vessels The Artificial Kidney Medical Need 60,000 people in the US are waiting for a kidney transplant. >600,000 suffer from Chronic Renal Disease (aka( End-Stage Renal Disease). Diabetes is the leading cause of kidney disease, with hypertension second. Kidney disease is the 9th leading cause of death in the U.S. Average cost of dialysis treatment $45,000 - $50,000/year. First year expenses associated with a kidney transplant average $100,000. Lack of kidney donors. Possible transplant rejection. Need more readily accessible, cheaper solution. The Artificial Kidney The Artificial Kidney The Human Kidney Function: to separate urea, minerals, salts, toxins, and other waste products from the blood. Conserve/regulate water, salts, and electrolytes. Active transport of Na +, PO 3-4, water by osmosis. Process controlled by release of ADH/vasopressin from posterior pituitary gland (in response to inc osmotic pressure from dehydration) Hemodialysis Blood is pumped through cellulose tubing immersed in dialysate fluid, and then back into the patient's vein. The membrane has a molecular-weight cut-off that will allow most solutes in the blood to pass out of the tubing but retain the proteins and cells. Anticoagulants are used. 2

3 The Artificial Kidney Hemodialysis techniques have improved with the advancement of membrane technology (ex. Hollow fibers) The Artificial Kidney Current Research Implantable kidney Small, can be attached in addition to kidney or after removal of a kidney. Some biocompatibility challenges remain Dialysis still requires sessions consisting of several hours of treatment. Natural kidneys produce some hormones and enzymes. These are not replaced by dialysis. New initiatives: Implantable artificial kidney Tissue engineered kidney From: International Renal Research, The Artificial Kidney Current Research Cell seeded tubule design Seed kidney cells within tubules. Synthetic tubules act as a scaffold. Tubules are used within a filtration cartridge. Results in improved compatibility and function. Tissue engineered kidney Use of human and porcine stem cells. Transplanted into mice. Must be harvested at specific time to develop into organized kidney tissue. Difficult, and immunological barriers remain. Laser Systems for Eye Surgery Medical Need Common ophthalmic conditions: Cataracts Treatment previously commonly made use of ultrasonic instruments to break up cataract. Success of technique relies heavily on operator. Can damage eye, or result in corneal edema. Corneal refractive errors (myopia, hyperopia, astigmatism and presbyopia) Often corrected by use of glasses or mechanical corrective procedures. In the year 2000, ~2 million refractive procedures worldwide. >90% were performed using laser technology. 3

4 Laser Systems for Eye Surgery Laser Systems for Eye Surgery The Human Eye Refractive surgery The Excimer Laser Some meta-stable compounds rapidly dissociate (under electrical stimulation) to the ground energy state of the individual molecules, releasing UV photons. The argon-fluorine molecule emits light with a wavelength of 193 nm. At this wavelength, ~0.25 µm m of corneal tissue is removed with each pulse. A human hair with grooves created using an eximer laser This laser can be used to correct malformations of the cornea Laser Systems for Eye Surgery Laser Systems for Eye Surgery Refractive surgery The LASIK procedure Combines a lamellar cut into the cornea (using a microkeratome) ) and corneal correction using the excimer laser. The cut creates a flap attached to the cornea. The flap is folded back, and heals without sutures. Advantages of Laser Treatment Extremely precise Noninvasive Surgery can be performed on an outpatient basis in a matter of minutes. Minimal pain or discomfort Short recovery time Reduction of postoperative complications (e.g. inflammation and infection) 4

5 Laser Systems for Eye Surgery Current Research Medical Need Attempts are being made to reduce uneven ablations that may be caused by beam inconsistencies. Eye tracking software is under development to produce increased precision. Better means for delivering drugs will increase the safety, efficacy, and specificity of therapeutic drug use. Eliminate over/under dosing. Increase convenience, ease of use. Reduce side effects. The Therapeutic Window 1) Mechanical Osmotic pumps Miniature infusion pump based on osmosis Drug released from reservoir at constant rate Often used in the laboratory setting Peristaltic pump Mechanical stimulation using rollers Often used in heart bypass machines or to pump nutrients into blood Asthma Inhaler Anti-inflammatories inflammatories,, and bronchodilators Pressurized canister with propellant 5

6 2) Polymers for drug delivery Controlled release Site specificity Applications: Oral, parenteral, transdermal,, implantable drug delivery Controlled Release Diffusion controlled Reservoir devices - Diffusion through membrane Monolithic or matrix devices - Diffusion through bulk polymer Water penetration controlled Swelling systems - Water penetration into polymer (ex. hydrogels) Chemically controlled Polymer degradation (surface erosion) or combination of erosion and diffusion (bulk erosion) Pendant chain systems - Combination of hydrolysis of pendant group and diffusion from bulk polymer Regulated systems Magnetic or ultrasound - External application of magnetic field or ultrasound to device Chemical - Use of competitive desorption or enzyme- substrate reactions. Environmentally triggered specificity Drug release may be triggered by environmental factors Ex. Glucose oxidase tethered to surface reacts with glucose, ph is reduced, polymer swells, insulin is released from reservoir Can be used for oral administration applications. Use of enteric coatings Most absorption in small intestine (higher ph than stomach) Current Research Tissue engineering Drugs can be released as polymer scaffold degrades Pharmacy on a chip Gold membrane covers wells on a chip. Drug can be released at the touch of a button. Langer et al 6

7 Synthetic Blood Vessels Synthetic Blood Vessels Medical Need Atherosclerosis is the most common cause of premature mortality in the Western World. >2 in 5 Americans will die of cardiovascular disease. Coronary artery atherosclerosis is estimated to cause over one million myocardial infarctions annually. Treatment consists of coronary artery bypass using autologous blood vessels to circumvent atherosclerotic occlusions. Each year half a million such surgeries are performed in the United States. Non ideal solution: Need suitable harvest site containing non essential, healthy blood vessel. Multiple vessels required for multiple bypass. Long term patency of venous grafts is significantly reduced by autologous graft atherosclerosis, damage caused by surgical manipulation, and susceptibility to infection. Human Artery Synthetic Blood Vessels Synthetic Blood Vessels Synthetic Grafts Use of Dacron and eptfe for large diameter grafts (<5mm). Surface grafted PEO. Surface grafted anticoagulants (ex heparin). Thrombolytic coatings (tpa( tpa). EC Seeded Grafts Idea is to seed endothelial cells onto a inner surface of polymeric scaffold, mimicking the inner surface of normal blood vessel. Hope to achieve anticoagulant properties. Use of cell adhesion peptides (RGD). Difficulty maintaining cells on surface when exposed to flow. State of endothelial cells (anti-coagulant?). Cell sourcing problem, time to develop. 20mm Dacron graft Heparin coated graft 7

8 Synthetic Blood Vessels Synthetic Blood Vessels Biological blood vessel Constructs mimicking the layers of a native blood vessel have been grown. Collagen shaped onto a tube to act as the medial layer. A layer of fibroblasts around the outside to act as the adventitial layer. Inner surface seeded with ECs to act as the intimal layer. But, not strong enough. Low burst pressure Constructs exposed to cyclic strain or pulsatile conditions Results in collagen and smooth muscle cells organization. Increased burst strength Difficult to reproduce consistently, extensive culture and maturation time, cell sourcing difficulties. Biodegradable scaffolds Stimulate tissue ingrowth in vivo Resorption must be time with tissue ingrowth to ensure maintenance of mechanical strength Use of copolymers One degrades quickly to stimulate ingrowth while other degrades slowly to maintain mechanical integrity Ex. PGA and PLA coplymers Tissue engineered blood vessels: En route to biological heart replacement?? Summary Questions/Comments New and improved medical devices are continually being developed. The artificial kidney, lasers in eye surgery, drug delivery devices, and vascular grafts are only a few examples of the many various medical devices. These devices are crucial to providing suitable health care services and improving our standard of living. 8