Sheep, pig and human platelet- material interactions with model cardiovascular biomaterials Steven L. Goodman Center for Biomaterials, University of Connecticut Health Center Presented by Andrew Thistle, Brian Choi, John Bocchino, Philip Kemp, and Timothy Hersey
Dr Steven L. Goodman • Professor of Biomaterials, Physiology, Biomedical Engineering and microscopy at University of Connecticut • Founded 10H Technology – Assists small company in obtaining governmental research funding
Journal of Biomedical Materials Research
Key Terms Thrombus - Also known as a blood clot, a thrombus is the final product of • the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form the platelet plug. Hemocompatibility - Tests the effects of blood contacting the bio- • materials, products, compounds, and on blood or blood components to see if they are compatible with an organism’s body. Pyrolytic Carbon - A material similar to graphite. Pyrolytic carbon is used • for biomedical applications because of its bio-compatibility and is thromboresistant. Rheological - The study of the flow of matter, primarily in liquid state, but • also as “soft solids” where the material responds with plastic flow rather than deforming elastically in response to an applied force. Topography -The study of surface shape and features • Elution - A term used in chemistry to describe the process of extracting • one material from another by washing with a solvent Pseudopodia - Temporary projections that extend and contract by the • reversible assembly of actin subunits into microfilaments. These projections allow a cell to move.
Introduction • Why did the researchers use sheep and pig in their experiments?
Animal Experimentation Pros : Cons : – No human deaths • Nonhuman species through experimentation differ from humans in – Can find cures for their responses to diseases/problems cardiovascular devices without risking human • Need to fully life understand the species to fully evaluate their predictive ability
Blood-Material Interaction • Focus: Sheep and Pig platelet adsorption to biomaterials compared to human platelet adhesion – See how different animal models spread and grow thrombi on different biomaterials • Platelet-mediated thrombosis may determine the success or failure of mechanical heart valves and other vascular prosthetics used in high-shear-rate locations
Biocompatibility • In Vitro studies have • Pyrolytic carbon (PYC) shown that human – Used in mechanical platelets attach and heart valves become extremely well – Topography is much rougher at the spread on PYC submicron scale – which • This indicates that PYC directly influences may not be as passive platelet adhesion to platelets as previously described
Purpose of the Study • Study the platelet responses of the two most often used large animals in cardiac valvular prosthetics: sheep and pigs – Shape of the platelet – Platelet adhesion – # of platelet cells per area
Materials Pyrolytic Carbon Formvar Polyethelene Silicone Rubber
Discussion Question 1 Why would you want to use 4 different materials that elicit different platelet responses?
Experimental Animal Species
Methods • Platelet response from the three different species were tested on the four materials • Wanted to determine which animals platelet response was most like humans • Platelet suspensions were purified and test materials were hydrated • Platelets were applied to each material and allowed to adhere for 45 min • The excess platelets were removed and the adhered platelets were incubated for another 45 min • This allowed the platelets to for the surface of the material • Electron microscopy was used to analyze platelet response
Discussion Question 2 The study used blood from adult humans and adult sheep, but juvenile pigs. Do you think this could have skewed the data? How so?
Results: Human Platelets PYC and PE FVR and SIL • Almost completely covered • FVR were extensively by spread platelets clustered into aggregates and minimally shape- • Platelets in direct material changed contact with PYC were spread to a greater extent • SIL induced minimal than those with PE spreading with dendritic forms (cohesion was • Both produced similar low essentially zero) levels of focal centers
Results: Sheep Platelets PYC and PE FVR and SIL • SIL induced greatest • PYC: mostly round and percentage of dendritic dendritic forms. • PE: similar to PYC with • FVR induced NO dendritic fewer spreading shapes spread. **Overall, level of response of sheep platelets was considerably less than humans
Results: Porcine Platelets PYC and PE FVR and SIL • PYC: platelets reached fully • SIL:Platelets were of round spread and spreading or dendritic shapes. morphologies • Lower deposition on SIL and • PE: Even distribution over FVR than PYC and PE material with dendritic and spread-dendritic shapes • **The extent of most porcine platelet responses was comparable to that of human platelets
Porcine Human Ovine
Discussion Question 3 Based on the adhesion properties of the different species of platelets, why were sheep, pig and human platelets used? Also, baboons were said to have similar properties – because they are most closely related to humans, why weren’t they used?
Discussion: Sheep • Large difference between the response of sheep and human platelets – Major difference: sheep platelets do not attach or spread to the same extent – Other differences: • Lower surface coverage • Less platelet interaction • Discussion Question : Using Figures 3-5 and other content within the article, what are some explanations for why there was such a minimal response of sheep platelets compared to human platelets for all measures (adherent platelets, cohesion, surface coverage, and focal centers)?
Discussion: Pigs • Pigs – Porcine platelets may be more similar to human platelets – More extensive “human- like” coverage and spreading observed on PYC – Results correspond closely to that of human platelets – More studies to be done using pig platelets
Discussion: Summary • Rank of material performance similar among all species: – Spreading: PYC greatest, slightly less for PE and FVR, and minimal responses to SIL (Table 1)
Major Conclusions • Sheep platelets are attenuated in response to biomaterials when compared to humans • Human platelets extremely spread on PYC – Based on in vitro studies, full spreading and surface coverage of human platelets may be important in the clinical biocompatability of PYC. • Porcine platelets had a similar response to human platelets – In vivo, porcine platelets may more closely model human responses – Porcine platelets on PYC in vivo can be used in future studies as a suitable model for examining platelet attachment and thrombosis on cardiovascular biomaterials
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