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Freezing-induced deformation of biomaterials in cryomedicine

Başlık çevirisi mevcut değil.

  1. Tez No: 606850
  2. Yazar: ALTUĞ ÖZÇELİKKALE
  3. Danışmanlar: DR. BUMSOO HAN
  4. Tez Türü: Doktora
  5. Konular: Biyomühendislik, Metalurji Mühendisliği, Tıbbi Biyoloji, Bioengineering, Metallurgical Engineering, Medical Biology
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2015
  8. Dil: İngilizce
  9. Üniversite: Purdue University
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 121

Özet

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Özet (Çeviri)

Cryomedicine utilizes low temperature treatments of biological proteins, cells and tissues for cryopreservation, materials processing and cryotherapy. Lack of proper understanding of cryodamage that occurs during these applications remains to be the primary bottleneck for development of successful tissue cryopreservation and cryosurgery procedures. An engineering approach based on a view of biological systems as functional biomaterials can help identify, predict and control the primary cryodamage mechanisms by developing an understanding of underlying freezing-induced biophysical processes. In particular, freezing constitutes the main structural/mechanical origin of cryodamage and results in signi cant deformation of biomaterials at multiple length scales. Understanding of these freezing-induced deformation processes and their e ects on post-thaw biomaterial functionality is currently lacking but will be critical to engineer improved cryomedicine procedures. This dissertation addresses this problem by presenting three separate but related studies of freezing-induced deformation at multiple length scales including nanometer-scale protein brils, single cells and whole tissues. A combination of rigorous experimentation and computational modeling is used to characterize post-thaw biomaterial structure and properties, predict biomaterial behavior and assess its post-thaw biological functionality. Firstly, freezing-induced damage on hierarchical extracellular matrix structure of collagen is investigated at molecular, bril and matrix levels. Results indicate to a speci c kind of bril damage due to freezing-induced expansion of intra brillar uid. This is followed by a study of freezing-induced cell and tissue deformation coupled with osmotically driven cellular water transport. Computational and semi empirical modeling of these processes indicate that intracellular deformation of the cell during freezing is heterogeneous and can interfere with cellular water transport, thereby leading to previously unconsidered mechanisms of cell freezing response. In addition, cellular water transport is identi ed as the critical limiting factor on the amount of freezing-induced tissue deformation, particularly in native tissues with high cell densities. Finally, e ects of cryopreservation on post-thaw biological functionality of collagen engineered tissue constructs is investigated where cell-matrix interactions during broblast migration are considered as the functional response. Simultaneous cell migration and extracellular matrix deformation are characterized. Results show diminished cell-matrix coupling by freeze/thaw accompanied by a subtle decrease in cell migration. A connection between these results and freezing-induced collagen bril damage is also suggested. Overall, this dissertation provides new fundamental knowledge on cryodamage mechanisms and a collection of novel multi-purpose engineering tools that will open the way for rational design of cryomedicine technologies.

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