To prevent clotting during dialysis, heparin is used to line the tubing which blood flows through. Unfortunately, many side effects arise from taking heparin, especially when it is used for an extended period of time. As such, long-term exposure for individuals undergoing dialysis every day is unavoidable. To prevent the solubilized heparin from entering the bloodstream, a polymer-based natural material is being investigated. This materials properties include reduction of coagulation and elimination of the long-term effects of heparin such as heparin induced thrombocytopenia and osteoporosis.
Cellulose nanocrystals (CNCs) contain the same 1,4 linked pyranose backbone structure as heparin along with desirable mechanical properties, like high stiffness and anisotropic shape. By altering the functionalization on the surface of CNCs to closely mirror that of heparin, it should be possible to make a biomimetic material that counteracts blood clotting, while not introducing soluble small molecule anti-coagulants into the body. Through blood assays and platelet fixing analysis, we have been able to show that this change in functionalization does reduce coagulation. Surface chemistry of CNCs were modified from 'plain' CNCs (70 mmol SO3-/kg residual from hydrolysis) to 500 mmol COO-/kg (TEMPO oxidized) and 330 mmol SO3-/kg CNC (sulfonated CNCs). We will show that by utilizing CNCs reactive functional groups and incredible mechanical properties we are able to create a material that reduces clotting while maintaining the tubing's mechanical strength as well as eliminating heparin's side effects associated with it being a soluble anticoagulant. / MS / To prevent clotting during dialysis, heparin is used to line the tubing which blood flows through. Heparin, an anticoagulant, is more commonly known as a ‘blood thinner’ which is a misnomer because it does not actually thin blood. Heparin works by inhibiting clotting factors in the coagulation cascade pathway which in turn limit the formation of blood clots and create the ‘thinning’ effect mentioned earlier. When dialysis is performed the interaction between blood and the dialyzer tubing initiates the formation of a blood clot. This is where heparin use comes in. Unfortunately, many side effects arise from taking heparin, especially when it is used for an extended period of time. As such, long-term exposure for individuals undergoing dialysis every day is unavoidable. To prevent heparin or its mimics from entering the bloodstream, a polymer-based natural material is being investigated. The properties of this material will include reduction of coagulation and elimination of the long-term effects of heparin.
The polymer-based natural material being investigated is cellulose nanocrystals (CNCs). CNCs contain the same ring structure and chemical linkage sites as heparin along with desirable mechanical properties. By altering the surface chemistry on the CNCs to closely mirror that of heparin, it should be possible to make a biomimetic material that counteracts blood clotting, while not introducing a solution based small molecule anticoagulant to the body. Through blood assays and platelet fixing analysis, we have been able to show that this change in functionalization does reduce coagulation. The ‘plain’ CNCs used contained an initial charge density of 70 mmol SO₃⁻ /kg. This residual charge density was a result from the acid hydrolysis performed to acquire CNCs from cellulose. Chemically modified CNCs contained many more negatively charged functional groups with TEMPO oxidized and sulfated CNCs having 500 mmol COO⁻/kg and 330 mmol SO₃⁻ /kg, respectively.
We will show that by utilizing CNCs reactive functional groups and incredible mechanical properties we are able to create a material that reduces clotting while maintaining the tubing’s mechanical strength as well as eliminating heparin’s side effects associated with it being a soluble anti-coagulant.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/102408 |
| Date | 27 August 2018 |
| Creators | Gallagher, Zahra Jane |
| Contributors | Materials Science and Engineering, Foster, Earl Johan, Goldstein, Aaron S, Ayres, Neil |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/x-zip-compressed |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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