The complex micro- and macro-structure of the meniscus requires a multidisciplinary approach to increase the knowledge currently available about the biology that characterizes its development. In the tissue of adult animals, it is possible to distinguish three zones according to the vascularisation, to the biochemical composition and to the regenerative abilities: 1) an outer zone, completely vascularised, with a fibrous-like matrix and capable of regenerating itself; 2) an intermediate zone with transitional characteristics; 3) an inner zone, non-vascularized, with a cartilaginous-like matrix and with poor repair capacity. Therefore, the meniscal tissue engineering, linking the structure and function of the tissues under normal conditions, seeks to develop a compound able to repair injuries of the inner zone, restoring the physiological characteristics to the tissue and avoiding degenerative phenomena. In particular, the aim of this PhD project was to analyse selected endogenous and exogenous factors that can influence the differentiation of meniscal cells. To do this, the project was divided into four parts: 1) role of hypoxia on chondrogenic differentiation of immature meniscal cells; 2) role of hypoxia on vascular factors involved in meniscus maturation; 3) role of endostatin on the chondrogenic differentiation of meniscus cells in a three-dimensional construct; and 4) characterization and validation of micro-computed tomography for the visualization of complex micro-structures such as the meniscal vascular network. Data were obtained through morphological, biochemical, biomechanical, molecular analyses and high-resolution imaging techniques.
La complessa micro- e macro- struttura del menisco richiede un approccio multidisciplinare per aumentare le conoscenze ad oggi disponibili circa la biologia che ne caratterizza lo sviluppo. Nel tessuto degli animali adulti è possibile distingue tre zone a seconda della vascolarizzazione, della composizione biochimica e delle capacità rigenerative: 1) zona esterna, completamente vascolarizzata, con matrice di tipo fibrosa e capace di rigenerarsi; 2) zona intermedia con caratteristiche di transizione; 3) zona interna, non vascolarizzata, con matrice di tipo cartilaginea e con scarse capacità di riparazione. Quindi, l’ingegneria del tessuto meniscale, legando struttura e funzione dei tessuti in condizioni normali, ha lo scopo di sviluppare sostituti biologici che creino un composto in grado di riparare lesioni della zona interna, restituendo al tessuto le caratteristiche fisiologiche ed evitando fenomeni degenerativi. In particolare, lo scopo di questo progetto di dottorato è stato analizzare i fattori endogeni ed esogeni che possono influenzare il differenziamento delle cellule meniscali. Per farlo, il progetto è stato suddiviso in quattro parti: 1) ruolo dell’ipossia sul differenziamento condrogenico di cellule meniscali immature; 2) ruolo dell’ipossia sui fattori vascolari coinvolti nella maturazione del menisco; 3) ruolo dell’endostatina sul differenziamento condrogenico di cellule menisco in un costrutto tridimensionale; e 4) caratterizzazione e validazione della tomografia micro-computerizzata per la visualizzazione di micro-strutture complesse quale è la rete vascolare meniscale. I dati sono stati ottenuti tramite analisi morfologiche, biochimiche, biomeccaniche, molecolari e tecniche di imaging ad alta risoluzione.
BASIC SCIENCE FOR TISSUE ENGINEERING IN VETERINARY ORTHOPAEDIC RESEARCH / V.r. Herrera Millar ; tutor: A. Di Giancamillo ; coordinatore: F. Ceciliani. Dipartimento di Scienze Biomediche per la Salute, 2023 Jul 13. 35. ciclo, Anno Accademico 2022.
BASIC SCIENCE FOR TISSUE ENGINEERING IN VETERINARY ORTHOPAEDIC RESEARCH
V.R. HERRERA MILLAR
2023
Abstract
The complex micro- and macro-structure of the meniscus requires a multidisciplinary approach to increase the knowledge currently available about the biology that characterizes its development. In the tissue of adult animals, it is possible to distinguish three zones according to the vascularisation, to the biochemical composition and to the regenerative abilities: 1) an outer zone, completely vascularised, with a fibrous-like matrix and capable of regenerating itself; 2) an intermediate zone with transitional characteristics; 3) an inner zone, non-vascularized, with a cartilaginous-like matrix and with poor repair capacity. Therefore, the meniscal tissue engineering, linking the structure and function of the tissues under normal conditions, seeks to develop a compound able to repair injuries of the inner zone, restoring the physiological characteristics to the tissue and avoiding degenerative phenomena. In particular, the aim of this PhD project was to analyse selected endogenous and exogenous factors that can influence the differentiation of meniscal cells. To do this, the project was divided into four parts: 1) role of hypoxia on chondrogenic differentiation of immature meniscal cells; 2) role of hypoxia on vascular factors involved in meniscus maturation; 3) role of endostatin on the chondrogenic differentiation of meniscus cells in a three-dimensional construct; and 4) characterization and validation of micro-computed tomography for the visualization of complex micro-structures such as the meniscal vascular network. Data were obtained through morphological, biochemical, biomechanical, molecular analyses and high-resolution imaging techniques.File | Dimensione | Formato | |
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phd_unimi_R12546.pdf
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Descrizione: Tesi di Dottorato di Valentina Herrera - Valentina Herrera Doctoral Thesis
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