De Gregorio, Maria
(2017)
Polymer bioactivation: a versatile tool to guide angiogenesis and tissue regeneration.
[Tesi di dottorato]
| Tipologia del documento: |
Tesi di dottorato
|
| Lingua: |
English |
| Titolo: |
Polymer bioactivation: a versatile tool to guide angiogenesis and tissue regeneration |
| Autori: |
| Autore | Email |
|---|
| De Gregorio, Maria | maria.degregorio@unina.it |
|
| Data: |
19 Maggio 2017 |
| Numero di pagine: |
58 |
| Istituzione: |
Università degli Studi di Napoli Federico II |
| Dipartimento: |
Medicina Veterinaria e Produzioni Animali |
| Dottorato: |
Biologia, patologia e igiene ambientale in medicina veterinaria |
| Ciclo di dottorato: |
29 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Cringoli, Giuseppe | giuseppe.cringoli@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Netti, Paolo Antonio | [non definito] | | Attanasio, Chiara | [non definito] |
|
| Data: |
19 Maggio 2017 |
| Numero di pagine: |
58 |
| Parole chiave: |
tissue engineering,angiogenesis, photopatterning |
| Settori scientifico-disciplinari del MIUR: |
Area 07 - Scienze agrarie e veterinarie > VET/01 - Anatomia degli animali domestici |
[error in script]
[error in script]
| Depositato il: |
03 Mag 2017 08:27 |
| Ultima modifica: |
07 Mar 2018 12:42 |
| URI: |
http://www.fedoa.unina.it/id/eprint/11689 |
Abstract
This PhD thesis stems from a research project conducted at the Center for Advanced
Biomaterials for Health Care/CRIB Istituto Italiano di Tecnologia in Naples (Italy).
The partial or total loss of organs and tissues is a major cause of hospitalization in
the world. The transplant is a possible therapeutic option for various degenerative
diseases for which it is not always possible a replacement therapy. However,
transplantation still suffers from a number of limitations that reduce its success.
Among them there are the need for lifelong immunosuppressive therapy, the risk of
infection at the site of transplantation and the shortage of organ donation. In this
context, a new science has emerged; it is tissue engineering (TE), which has quickly
become a key research area in the field of regenerative medicine. TE is a
multidisciplinary science that includes the principles of chemistry, biochemistry,
medicine, engineering and physics, in order to provide engineered tissues to restore
the lost function of damaged tissues and organs. This discipline combines scaffolds,
biologically active molecules and cells to build functional tissues. During
regeneration it is crucial for a tissue to receive the right amount of O2 and nutrients.
For this reason, one of the main goals of TE is to induce the formation of a functional
vascular network. The aim of this project is to enhance the ability of bioactive
polymeric matrices to guide regeneration through the spatial and temporal control
of the angiogenesis process. In this perspective, I have been involved in different
activities including scaffold design and fabrication but particularly the study of its
performance from a biological standpoint. Aiming to guide angiogenesis in a space
and time controlled fashion we produced scaffolds with controlled porosity and
suitable to be loaded with vascular growth factors in order to generate a
biochemical gradient. To this purpose scaffolds were fabricated using two different
techniques: random assembly, which implies an uncontrolled porosity, and ordered
assembly, which includes a controlled porosity. Afterwards, I moved to the
comprehension and the validation of the interplay between the scaffold and the
cells as well as between the scaffold and the host tissue after implantation.
Besides biochemical signals, or rather gradients of these signals, several studies
show that endothelial cells are particularly influenced by topographic cues coming
from the extracellular matrix. In view of this, I decided to investigate if these signals
are able to guide sprouting angiogenesis in a space and time controlled manner
without the use of growth factors. To this aim, to resemble physiological signals
which are intrinsically dynamic, we used a photoswitches-based strategy to modify
the surface of a s specific biomaterial, through a reversible photochemical
technique.
Finally, since in the past I was involved in studies focused on the use of Carbon
Monoxide (CO) to restore the organ function after ischemia/reperfusion injury, I
hypothesized that the advantages related to the use of polymer nanocarriers may
contribute to solve the open challenges related to the use of this gas in the clinical
practice.
Several studies, actually, revealed the positive effects of CO in the restoration of the
organ function after injury (liver, kidney, heart and others), however this molecule is
still considered mostly a toxic gas. In addition, its therapeutic use is hampered by
the difficulty to modulate its administration. CO, indeed, is slightly soluble in water
so that to reach therapeutic concentrations it should be inhaled at high doses
becoming, therefore, dangerous. These issues have been partially overcome through
the introduction of the so-called CO-releasing molecules (CORMs). These
compounds are able to release CO in the blood, nevertheless, the release is still too
fast. In this context is the hypothesis to test, in a model of liver damage, the effect
of CORMs encapsulated in polymer nanoparticles able to vehiculate and release
them in a controlled manner in order to encourage liver regeneration.
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