
University of Lund
1.
De Santis, Martina M.
Next generation bioengineering of lung tissue for
transplantation.
Degree: 2021, University of Lund
URL: https://lup.lub.lu.se/record/eaaf4197-e6f1-4af4-9baf-30816410fe31
;
https://portal.research.lu.se/ws/files/90537869/Martina_De_Santis_Dissertation_Web.pdf
Lung transplantation is the only option for
end-stage lung diseases, but organ shortage remains problematic.
Generating lungs ex vivo could overcome shortages with current
approaches being explored for lung tissue engineering utilizing a
biologically derived, synthetic or hybrid scaffold which is seeded
with cells and cultured ex vivo. Ideally, cells could be sourced
from the transplant recipient and thus are conceptualized to reduce
the long-term requirements for immunosuppressive drugs and the risk
for rejection. Progenitor cell populations can be controlled more
easily than induced pluripotent stem cells (IPSCs), with lower risk
of tumour formation. However, as presented in this thesis,
progenitor cells can be deranged in diseased lungs such as for
example idiopathic pulmonary fibrosis (IPF) and are therefore
unlikely candidates to generate healthy tissue. In addition to
healthy cells, scaffolds with attributes known to be
pro-regenerative are required to generate healthy tissues. In the
thesis it is shown that both scaffold and cell age plays a role in
the regenerative capacity of a tissue. From this it is clear that
to generate a healthy tissue or organ, it is critical to find the
appropriate scaffold and cell type. Additionally, bioengineering
manufacturing methods that generate reproducible, custom-made, high
resolution constructs using cytocompatible materials are ideal for
tissue engineering approaches. One such method which is compatible
with the criteria above and that has emerged in recent years is 3D
printing. 3D printing or bioprinting (when cells are printed) can
generate custom structures relevant for human lungs. In this
thesis, potential bioinks for bioprinting lung tissue are
investigated. A tissue-specific hybrid bioink consisting of
alginate, reinforced with extracellular matrix from decellularized
lung tissue (rECM) was used to 3D bioprint human airways comprised
of regionally specified primary cells which remained patent over
time. The biocompatibility and vascularisation of rECM hydrogels
was investigated in both T-cell immunodeficient mice mimicking the
clinical scenario and immunocompetent mice. Bioprinted rECM
hydrogels support the formation of an intact vascular network
throughout the full thickness of the graft, comprised of both large
and small size blood vessels and integrate well in the surrounding
tissue.
Subjects/Keywords: Cell and Molecular Biology
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APA (6th Edition):
De Santis, M. M. (2021). Next generation bioengineering of lung tissue for
transplantation. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/eaaf4197-e6f1-4af4-9baf-30816410fe31 ; https://portal.research.lu.se/ws/files/90537869/Martina_De_Santis_Dissertation_Web.pdf
Chicago Manual of Style (16th Edition):
De Santis, Martina M. “Next generation bioengineering of lung tissue for
transplantation.” 2021. Doctoral Dissertation, University of Lund. Accessed March 01, 2021.
https://lup.lub.lu.se/record/eaaf4197-e6f1-4af4-9baf-30816410fe31 ; https://portal.research.lu.se/ws/files/90537869/Martina_De_Santis_Dissertation_Web.pdf.
MLA Handbook (7th Edition):
De Santis, Martina M. “Next generation bioengineering of lung tissue for
transplantation.” 2021. Web. 01 Mar 2021.
Vancouver:
De Santis MM. Next generation bioengineering of lung tissue for
transplantation. [Internet] [Doctoral dissertation]. University of Lund; 2021. [cited 2021 Mar 01].
Available from: https://lup.lub.lu.se/record/eaaf4197-e6f1-4af4-9baf-30816410fe31 ; https://portal.research.lu.se/ws/files/90537869/Martina_De_Santis_Dissertation_Web.pdf.
Council of Science Editors:
De Santis MM. Next generation bioengineering of lung tissue for
transplantation. [Doctoral Dissertation]. University of Lund; 2021. Available from: https://lup.lub.lu.se/record/eaaf4197-e6f1-4af4-9baf-30816410fe31 ; https://portal.research.lu.se/ws/files/90537869/Martina_De_Santis_Dissertation_Web.pdf