Biomaterial Applications Flashcards
Mechanical Heart Valve
Mechanical prosthetic heart valves are composed of non-physiologic biomaterials that employ:
(1) rigid mobile occluders in a metallic cage out of cobalt-chrome or titanium alloy (Bjork-Shiley, Hall-Medtronic, and OmniScience valves)
(2) two carbon hemidisks in a carbon housing (St. Jude Medical (the most widely used), CarboMedics CPHV, Medical Carbon Research Institute, or On-X prostheses).
- Today, all mechanical valve occluders are fabricated from pyrolytic carbon.
- Pyrolytic carbon has high strength, fatigue and wear resistance, and exceptional biocompatibility, including relative thromboresistence. Generally favorable durability.
- Patients receiving mechanical valves must be treated with lifelong anticoagulation to reduce the risk of thrombosis and thromboembolic events.
Tissue Heart Valves
- Having a trileaflet configuration with a central orifice, tissue valves resemble natural valves.
- The term “bioprosthesis” describes a special type of tissue valve composed of three cusps of tissue derived from animals— most frequently either a porcine (pig) aortic valve or bovine (cow) pericardium—each treated with glutaraldehyde.
- Glutaraldehyde fixation preserves the tissue, decreases its (already relatively low) immunological reactivity, and kills the cells within the valve tissue.
- No immunosuppression is required for these xenografts as is required for whole organ transplants (e.g., kidney, liver, or heart).
- However, since these valves no longer contain viable cells, the cusps them- selves cannot remodel or respond to injury as does normal tissue.
- Fabricated tissue valve cusps are usually mounted on a metal or plastic stent with three posts (or struts) to simulate the geometry of a native semilunar valve.
- As with mechanical valves, the base ring is covered by a Dacron- or Teflon-covered sewing cuff to facilitate surgical implanta- tion and healing.
- The most widely used valve type is the Carpentier-Edwards pericardial valve.
Cardiovascular applications: Heart Valves
The three generic components comprise the key parts of all previous and present surgical heart valve prostheses: (1) moving part (either synthetic or biologic)
(2) superstructure to guide the motion of the moving occluder
(3) sewing cuff (anchored at the anastomotic site)
Desired properties of a biomaterial to be used in a heart valve prosthesis:
- high-stress resistant
- long-lasting (fatigue resistant)
- non-fouling (anti-platelet, non-thrombotic) (biocompatibility)
- shear strength
- flexible
- The idealised prosthetic heart valve must closely mimic the characteristics of the native heart valve, offering regular hemodynamics, thromboresistance, biological and mechanical resistance, and of course be implantable.
- This is predominantly influenced by the choice of biomaterial.
- Virchow’s triad (surface thrombogenicity, hyper-coagulability, and locally static blood flow) largely predicts the relative propensity of a device to thrombus formation and location of thrombotic deposits with cardiovascular prostheses.
Allografts/Homografts
- Tissue valves derived from human cadaveric aortic or pulmonary valves with or without the associated vascular conduit.
- These valves have good hemodynamic profiles, a low incidence of thromboembolic complications without chronic anticoagulation, and a low reinfection rate following valve replacement for endocarditis.
- Now cryopreserved rather than chemically preserved to combat high rate of leaflet calcification and rupture.
- Contemporary allograft valves yield freedom from degeneration and tissue failure equal to or better than those of conventional porcine bio- prosthetic valves, but their use is limited by availability, difficulty in obtaining the proper size, and a more complex surgical procedure for implantation.
Percutaneous Transcatheter Valves
- However, a substantial fraction of patients with aortic stenosis, estimated to be 30%–40% overall, is deemed unsuitable for surgical aortic valve replace- ment because of advanced age, frailty, and often multiple comorbidities.
- Minimally invasive alternative to conventional aortic valve replacement, called transcatheter aortic valve implantation (TAVI), which was initially used clinically in 2002, and has extended the opportunity for effective mechanical correction of valve disease to a potentially large population of otherwise untreatable individuals.
- The delivery strategy involves collapsing the device and placing it within a catheter-based sheath; for balloon expandable devices, they must be collapsed over a balloon.
- The devices used in transcatheter valve implantation have an outer stent-like structure that contains leaflets.
- The stent holds open a valve annulus and resists the tendency of a valve annulus or diseased native leaflets to recoil following balloon dilation, supports the valve leaflets, and provides the means for seating the prosthesis in the annulus.
- The stents are made from self-expandable stainless steel, platinum-iridium, or other alloys, or shape-memory materials such as nickel-titanium alloys (e.g., Nitinol).
- Tissues used for the valve component include bovine, equine, or porcine pericardium and bovine jugular venous valves.
Endovascular Stents
- Stent: an expandable tube of metallic mesh that splints open the vessel wall. (must be flexible)
- Used to restore blood flow through a diseased portion of the coronary circulation in patients with acute (typically due to thrombus) or chronic (typically due to progressive atherosclerosis) occlusion causing stable angina (chest pain due to cardiac ischemia occurring during exercise and resolving at rest), unstable angina (similar chest pain but also occurring at rest), or acute myocardial infarction (heart attack).
- Stents preserve luminal patency by limiting elastic recoil and mechanically preventing vascular spasm.
- They provide a scaffold to support the disrupted vascular wall and increase blood flow, thus minimizing thrombus formation and restenosis.
- Endoluminal stents also provide a means of delivering any localized therapy intended to reduce restenosis, such as a pharmacologic agent or radiation.
- –> Particularly has had to be utilised, due to the most important early complication of bare metal (316L stainless steel, which required balloon expansion, or nitinol, an alloy of nickel and titanium that is self-expanding by virtue of its “shape memory” characteristics (i.e., the stent is compressed into the delivering catheter at room temperature, and then spontaneously recovers its original, undeformed, expanded stent shape upon removal of the delivery sheath at body temperature) stenting being thrombosis.
- –> stents coated with polymer containing either rapamycin (sirolimus) or paclitaxel.
- Resorbable/biodegradable stents are another option, made of poly-l-lactide (clinically trialed), providing a scaffold to support vessel expansion and then ultimately disappearing by resorption of the foreign material that may potentiate a thrombotic event.
- May potentially mitigate the problems of late thrombosis, vessel distortion, and interference with surgical coronary arterial revascularization.
- Have been the subject of extensive research and development efforts in recent years.
- The choice of stent is based on several factors, including the characteristics of a given plaque, such as diameter, length, and location within the coronary anatomy, and the experience of the interventional cardiologist with a particular stent.
Vascular grafts
- Used to bypass an obstructed vessel or replace a segment of vessel.
- Choice of material must:
(1) have mechanical compliance consistent with the vessel it is replacing.
(2) be resistant to thrombus to prevent occlusion.
(3) resistant to tissue overgrowth causing intimal hyperplasia (particularly at an anastomosis).
(4) have a sufficient level of suturability to facilitate placement.
(4) be fatigue resistant (i.e., durable). - In general, large-diameter (12–18mm) synthetic fabric grafts currently used in high- flow, low-resistance locations such as the aorta, the iliac and proximal femoral arteries, and aorto-femoral bypass gener- ally have good clinical outcomes, with 5–10-year patency rates of 90%.
- In contrast, small-diameter synthetic vascular grafts (less than 6–8 mm in diameter) generally perform less well with 5-year patency less than 50%.
- Moreover, tissue grafts (especially autologous tissue) generally outperform synthetic grafts in small-diameter locations.
- One method to address lack of extensive neointima (endothelial cells coating initially developed platelet-fibrin-rich layer, serving as a nonthrombogenic surface) formation within most of the graft has been to create fabric grafts that have sufficient transwall porosity.
- -> can be impregnated with proteins to aid clotting, reduce blood loss and stimulate in growth.
Ophthalmologic applications: Contact lens’
- Similar to materials used in other areas of the body, bio- compatibility, stability, degradation, sterilizability, and manufacturability all must be considered in biomaterial choice.
- Uniquely, optical properties are particularly critical for ophthalmologic application.
- The materials must be transparent, with a refractive index that is equal to or greater than the tissue that is being replaced.
- UV-blocking agents may be incorporated into these materials in order to protect the delicate retina from UV light exposure.
- Any material used in the cornea, such as a contact lens or a corneal inlay, must have sufficient oxygen and nutrient permeability to allow for the maintenance of corneal health due to the lack of vascularisation of this tissue.
Contact lens materials
There are two main categories of contact lenses that are grouped by their basic mechanical properties.
HARD CONTACT LENSES
- rigid materials with a high modulus, generally containing either silicone or fluorine derivatives to allow for oxygen permeation.
- Specifically, originally made from poly(methyl methacrylate) (PMMA).
- now copolymers of PMMA, functionalized with silicone- and fluorine-containing macromers.
- currently marketed hard contact lenses mainly consist of perfluoroalkyl-siloxyanylalkyl-methyl methacrylate type materials which have both a high Dk (measure of gas permeability) and appropriate surface properties.
SOFT CONTACT LENSES
- hydrogel materials with a low modulus and higher water content.
- Due to the water content of hydrogels, and their result- ing low modulus, highly comfortable.
- Conventional materials are typically made of more hydrophilic monomers… limited in terms of their ability to be worn overnight or for an extended period, with the risk of adverse effects increasing more than fourfold with extended wear.
- Silicone hydrogels are newer materials that contain a hydrophobic but oxygen-permeable siloxane component . to overcome the limitations of these materials while maintaining comfort.
—> hydrophobicity decreases their wettability, leading to increased biofouling and the need for surface modification to alter the surface properties.
- The first silicone hydrogels on the market were plasma treated to alter the surface properties without adversely affecting the bulk.
- Plasma oxidation creates glassy silicate islands on the lens surface with properties such that a hydrophilic surface is generated without altering the bulk properties of the material.
- Alternatively, plasma coating of a hydrophilic polymer approximately 25nm thick can be applied, lowering the mobility of the underlying silicone layer and minimizing the reorientation of the silicones to the surface.
- Increases the lens modulus due to lack of chain mobility, leading to stiffer materials.
- Ultimately faced with a tradeoff between gas permeability and mechanical stability.
Components of Tissue engineering (CELLS/BIOLOGICAL FACTORS)
(1) cells
(2) a physical template (scaffold)
(3) a combination of biological cues that promote regeneration and integration of the construct into a functional and organized tissue.
CELLS:
- the building blocks of tissues and play a critical role in promoting tissue healing and regeneration.
Multiple variables should be addressed in the selection of the best stem cell population, including:
(1) stem cell accessibility (e.g., the isolation of autologous or allogenic neural stem cells is invasive and relatively difficult compared to other stem cells);
(2) number of cells needed, where undesired differentiation during expansion has to be prevented;
(3) proliferation capacity, where extra resources and expertise are needed for cells with limited proliferation;
(4) differentiation profile;
(5) cell population purity, depending on whether the cell source is a specific tissue or differentiated from pluripotent/stem cells, population homogeneity, and purity;
(6) absence of random mutations that can potentially cause uncontrolled proliferation and tumors;
(7) ethical issues.
BIOLOGICAL FACTORS
- Satisfy a broad category, including hormones, cytokines, growth factors, ECM molecules, cell surface molecules, and nucleic acids.
- A large number of biomolecules have been explored to induce tissue regeneration and can be broadly categorized as follows
(1) small molecules (e.g., corticosteroids, hormones) are used for intercellular and intracellular signaling by binding to specific protein receptors;
(2) proteins and peptides act on the cells as mitogens, morphogens, growth factors, and cytokines where they bind to a target cell receptor, triggering an intracellular signal transduction and a biological response;
(3) oligonucleotides (DNA or RNA) can affect either gene transcription and/or translation or can be incorporated into the cell’s genome.
Scaffold biomaterial requirements
- act as the synthetic analog of the natural ECM.
- The role of scaffolds is to recapitulate the normal tissue development process by allowing cells to formulate their own microenvironment.
- Ideally, a scaffold should have the following characteristics:
(1) 3D highly porous structure with an interconnected pore network to facilitate cell/tissue growth and diffusion of nutrients, metabolic waste, and paracrine factors;
(2) biodegradable or bioresorbable features with controllable degradation and resorption rates to match cell/ tissue growth in vitro and in vivo;
(3) suitable surface chemistry for cell attachment, proliferation, and differentiation;
(4) mechanical properties to match those of the tissues at the site of implantation;
(5) easy processability to form a variety of shapes and sizes. - Natural materials: A wide range of natural-origin poly- mers, generally including proteins and polysaccharides, are used as carriers for cells and bioactive molecules.
- Natural materials are advantageous due to their inherent biological recognition through receptor– ligand interactions, cell-mediated proteolysis and remodel- ing, and low toxicity.
- limitations of natural materials include purification, cost, immunogenic responses, and lack of control over mechanical properties. There also exists the potential for a natural polymer to carry microbes or viruses.
Decellularized extracellular matrix: Decellularizing tissues, a process that eliminates all cellular and nuclear materials with various detergents, and using the remaining matrix as building blocks for therapeutic purposes, has provided a facilitated approach that contains critical physical and chemical properties for site-specific tissue regeneration.
Synthetic materials: Many synthetic polymers have been designed and fabricated for tissue-engineering purposes. Biodegradable synthetic polymers offer several advantages compared to natural materials such as controlled mechanical properties and degradation kinetics, easy processability into custom shapes and structures, and easy modification of the material for specific applications.
- Saturated aliphatic polyesters, such as polylactide (PLA), polyglycolide (PGA), and poly(caprolactone) (PCL), are the most commonly used biodegradable synthetic polymers for 3D scaffolds in tissue engineering.
