The PRINCIPLES OF IMPLANT DESIGN [Autosaved].pptx

Implants

1. PRINCIPLES OF IMPLANT DESIGN Medical implants are devices or tissues that are placed inside or on the surface of the body. Many implants are prosthetics, intended to replace missing body parts. Other implants deliver medication, monitor body functions, or provide support to organs and tissues. Some implants are made from skin, bone or other body tissues.  Others are made from metal, plastic, ceramic or other materials. Implants can be placed permanently or they can be removed once they are no longer needed. For example, stents or hip implants are intended to be permanent.  But chemotherapy ports or screws to repair broken bones can be removed when they no longer needed.

2. Irreversible organ injury The mammalian fetus regenerates lost organs spontaneously. • Adult mammals do not regenerate damaged or diseased organs. • The adult response to trauma or chronic disease includes wound closure by contraction and formation of scar (repair) Example of adult healing response. Severe burn causes skin loss. Wound closes by contraction and scar synthesis Poor organ function leads to unpleasant choices, scarred heart muscle: poor pumping action; congestive heart failure; drugs, heart transplant scarred kidney: poor filtration; use kidney dialysis machine scarred heart valve: inefficient pumping due to leaky valve; congestive heart failure scarred liver: cirrhosis; poor function; liver transplant scarred eye: loss of vision

3. Approaches to missing organ Transplantation (e.g., kidney transplant, heart transplant) donor organ donor ⇒⇒⇒⇒ host ⇒rejection? ⇒ ⇒ treatment Challenges (impairs immune system Also, demand for organ transplants greatly outstrips supply) 2) Autografting (e.g., heart bypass, skin grafting) Donor = recipient Example: In heart bypass surgery, a length of leg vein is removed and used to shunt clotted coronary artery. There is sufficient recovery of function. Passive Implant (e.g., hip prosthesis, pacemaker) metallics/polymers/ceramics ⇒ device fabrication ⇒ host ⇒ long-term function? materials used: stainless steel, Ti alloys, CoCr alloys, polylactic acid, polyglycolic acid, nylon; dacron (PET) vascular graft; polyurethane heart chamber

4. Challenges Problem #1: host attacks implant e.g a) migration of hip prosthesis b) abrasion of polyethylene 'cup’ c) tissue fluid attacks pacemaker electronics Problem #2: implant attacks host e.g a) hip prosthesis causes bone loss (stress shielding) b) heart valve causes blood cell rupture c) vascular graft causes blood clotting In vitro synthesis Synthesize a construct resembling the desired organ (organoid) in vitro in the presence of cells of one or more types, solutions of cytokines and one or more scaffolds. Implant the organoid at the correct anatomical site. If successfully synthesized, the organoid becomes incorporated in the organism and functions physiologically. Problem: Physiological cytokine field unknown, cannot be replicated in vitro

5. Implant design Design strategy Analyze problem of irreversible injured organ by identifying tissues in organs that regenerate spontaneously (regenerative) and those that do not (nonregenerative). Rather than planning a device that can synthesize the entire organ, the designer’s task is made simpler if the design focuses on synthesis of just those tissue(s) that do not regenerate by themselves. Which are they? Identify nonregenerative tissues Every organ is different, but…. Generalize by focusing on individual tissues that comprise organ. Most organs are made up of three basic tissues (“tissue triad”): epithelia, basement membrane, and stroma. Epithelia and basement membrane are spontaneously regenerative; the stroma is not. Therefore, the central problem in biomaterials selection for organ replacement by regeneration is synthesis of the stroma

6. Members of the tissue triad EPITHELIA 100% cells. No matrix. No blood vessels. • BASEMENT MEMBRANE No cells. 100% matrix. No blood vessels. STROMA (CONNECTIVE TISSUE) Cells. Matrix. Blood vessels.

7. Note Epithelia and basement membrane (BM) are synthesized from remaining epithelial cells. The stroma is not synthesized from remaining stromal cells. Instead these cells induce closure of the injury by contraction and synthesis of scar. Therefore, the key process is synthesis of the stroma. • Once the stroma has been synthesized, epithelial cells can synthesize both epithelia and BM over it (“sequential” synthesis). • Also, consider “simultaneous” synthesis .

8. Paradigm for implant design

9. Tissue engineering Overview Tissue is a biological is a biological structure made up of cells of the same type. of the same type. I.e. Cells of the same phenotype (i.e., same genes ., same genes expressed) An aggregation of morphologically similar cells and associated extracellular matrix acting together to perform one or more specific functions in the body. There are four basic types of tissue: muscle, nerve, epithelia, and connective. An organ is a structure made up of 2 or more tissues.

10. Tissue formation processes Embryonic tissue formation Tissue growth and development (fetal and postnatal) Remodeling (degradation-formation) Healing (repair versus regeneration) Repair: defect in the tissue fills with “scar” (generally fibrous tissue Regeneration: defect fills with tissue that is indistinguishable from the original tissue

11. What is tissue engineering? Production of tissue in vitro by growing cells in porous, absorbable scaffold. Why is tissue engineering necessary? Most tissues cannot regenerate when injured or diseased. Even tissues that can regenerate spontaneously may not completely do so in large defects (e.g., bone). Replacement of tissue with permanent implants is greatly limited Problems with Tissue Engineering Most tissues cannot yet be produced by tissue engineering ( in vitro). Implantation of tissues produced in vitro may not remodel in vivo and may not become integrated with (bonded to) host tissue in the body. Solution Use of implants to facilitate formation (regeneration) of tissue in vivo. – “Regenerative Medicine” – Scaffold-based regenerative medicine.

12. Tissue engineering versus regenerative medicine TISSUE ENGINEERING Regeneration In Vitro Produce the fully formed tissue in vitro by seeding cells into a biomaterial matrix, and then implant the regenerated tissue into the body. REGENERATIVE MED. Regeneration In Vivo Implant the biomaterial with, or without seeded cells, into the body to facilitate regeneration of the tissue in vivo.

13. TISSUE ENGINEERING Regeneration In Vitro Advantages Evaluation of tissue prior to implantation prior to implantation Disadvantages For incorporation, must be remodeling Stress-induced induced architecture cannot yet be produced in vitro

14. REGENERATIVE MED Regeneration In Vivo Advantages Incorporation and formation under the influence of endogenous regulat (including mechanical strains) Disadvantages Dislodgment and degradation by mechanical stresses in vivo

15. Factors that can prevent regeneration Size of defect – e.g., bone does not regenerate in large defects Collapse of surrounding tissue into the defect – e.g., periodontal defects Excessive strains in the reparative tissue – e.g., unstable fractures

16. Effects of implant on body Chemical Molecules/Ions Released (Toxicity) either by direct effects of molecules/ions on cells or by binding of molecules/ions to proteins to form complexes that elicit adverse biological response. Alteration of Adsorbed Macromolecules causing them to have an Adverse Effect either by Changing in conformation of adsorbed proteins (e.g., on hydrophobic surfaces) causing them to be immunogenic or Cleavage/fragmentation of adsorbed proteins such as complement molecules thus activating the alternative pathway of the immune response B. Mechanical: Alteration on Strains in Surrounding Tissue ("Modulus Mismatch") Electrical; Electrically conducting implants might short out "strain generated potentials" in surrounding tissues (e.g., bone)? Electrical currents produced by the device (e.g., pacemakers) could adversely affect cells. Thermal; Heat resulting from exothermic polymerization reactions (e.g., PMMA-"bone cement") can cause tissue necrosis. Thermal conductivity and heat capacity (i.e., thermal diffusivity) could affect how heat generated by implants (e.g., functional heat from artificial joints) is dissipated?

17. Effect of body on implants Chemical Corrosion of metals: metal ion release due to an anodic (reduction) reaction a) Pitting and crevice corrosion and "concentration cell" effect at sites of depleted oxygen b) Galvanic corrosion due to contact of dissimilar metal. The more reactive metal (in the Galvanic series) becomes the anode. c) Stress corrosion due to accelerated metal ion release at a crack tip where the strain is high. d) The oxide "passivation" layer reduces potential for corrosion. e) Corrosion facilitates cracks initiation and thereby weakens the device. f) Ranked according to their potential for corrosion: Stainless steel > Co-Cr alloy > Ti alloy.

18. . Oxidation of polymers; Oxidation of polyethylene results in chain scission and a reduction in the average molecular weight. This causes increases in the density, modulus of elasticity, and percent crystallinity. Oxidation can be determined by detecting the carbonyl groups that are formed. Hydrolysis of polymers; Ester linkages (e.g., polylactic and polyglycolic acid) are attacked by water leading to chain scission. Water absorption; Water absorption can lead to an alteration in the mechanical properties of certain hydrophilic thermoplastic polymers (e.g., polysulfone). Lipid absorption; Absorption of lipid by certain hydrophobic polymers (e.g., polydimethyl siloxane). Dissolution; The effect of water and pH in dissolving certain substances (e.g., calcium phosphates) Precipitation; Deposition of calcium salts (calcification). Enzymolysis; Natural polymers (e.g., collagen) used as an implant materials can undergo degradation as a result of the action of enzymes (e.g., collagenase).

19. Mechanical : Mechanical loading applied by the body can lead to wear (erosion) and fatigue fracture of the device. 1. Fatigue testing of implants. Wear due to rubbing of tissue (viz., bone) against the device.

20. CARDIAC IMPLANT Cardiac implantable electronic devices, including  pacemakers, implantable cardioverter defibrillator (ICD), biventricular pacemakers, and cardiac loop recorders , are designed to help control or monitor irregular heartbeats in people with certain heart rhythm disorders and heart failure. If you have received a diagnosis of  bradycardia ,  ventricular arrhythmia, or supraventricular arrhythmia  such as  atrial fibrillation and atrial flutter , your doctor may recommend that you receive one of these devices. After the device is placed, it continuously collects information about your heart rhythm. This information is transmitted wirelessly to our cardiac device team, either automatically, through prescheduled transmissions, or manually, when you notice symptoms.  Remote monitoring  allows us to review your heart’s electrical activity as needed, without the need for a doctor’s visit.

21. Examples include Pacemaker Implants Some types of abnormal heart rhythms can only be treated effectively with an artificial pacemaker. The latest technology in pacemakers offer models that weigh only about 1.5 ounces and contain a lithium battery that can last up to 10 years. The pacemaker unit is implanted surgically beneath the skin just below the collarbone on the right side of the chest. Cardioverter Defibrillators (ICD's) Implants ICD's are small automatic devices that can detect and treat arrhythmias in patients with ventricular tachycardia and ventricular fibrillation, where the heart beats dangerously fast. Today's device consists of a generator slightly smaller than the size of a wallet attached to electrode catheters. The defibrillator is surgically placed under or over chest or abdominal muscles, and the catheters are threaded through veins to permanent positions in the heart. The implanted defibrillator monitors the heart rhythm and automatically detects and treats abnormal rhythm with electrical shock. 3) Loop Recorder Insertion The implantable loop recorder, smaller than a pack of gum, is inserted just beneath the skin in the upper chest area. The recorder continuously monitors the rate and rhythm of the heart 24 hours a day. Episodes of fainting and other symptoms are recorded and can be played back later for detailed analysis. 4) WATCHMAN Device The WATCHMAN Device is intended for percutaneous, transcatheter closure of the left atrial appendage (LAA). Patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism, are not suitable for long term warfarin therapy, and seek a non-pharmacologic alternative may be eligible for a WATCHMAN Device.

22. Biventricular pacemaker A biventricular pacemaker works like a conventional pacemaker but uses a third wire to send electrical impulses to the heart to resynchronize the contractions of the heart’s left lower chambers, or ventricles. Also called a cardiac resynchronization device, a biventricular pacemaker is implanted when medications don’t relieve symptoms of heart failure, a condition in which the heart does not pump a sufficient amount of blood to the body, and when the left chamber does not beat in a coordinated manner. This causes the two ventricles to contract out of sync with one another. A resynchronization device coordinates the contractions of the left ventricle. There are also biventricular defibrillators for people who would benefit from resynchronization yet also require the protection of a defibrillator. This combination device works to maintain a steady heartbeat and either speed up or slow down a heart that is beating too slow or too fast. It also records information about your heart rhythm, so our specialists can evaluate your heart health and adjust treatment as needed.

23. Question???? Give five advantages and disadvantages of cardiac implants.

24. COURSEWORK Explain 10 clinical problems requiring implants for solution, and mention available solution for each of them. Design an implant solving any clinical problem of your choice. NOTE: Your expected to hand in this work on 14 th of April 2022