Biomimetic Scaffolds for the Controlled Release of Bioactive Molecules for Tissue Engineering Applications

Minardi, Silvia (2015) Biomimetic Scaffolds for the Controlled Release of Bioactive Molecules for Tissue Engineering Applications, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Chimica, 27 Ciclo. DOI 10.6092/unibo/amsdottorato/6859.
Documenti full-text disponibili:
Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Download (6MB) | Anteprima


The temporospatial controlled delivery of growth factors is crucial to trigger the desired healing mechanisms in target tissues. The uncontrolled release of growth factors has been demonstrated to cause severe side effects in its surrounding tissues. Thus, the first working hypothesis was to tune and optimize a newly developed multiscale delivery platform based on a nanostructured silicon particle core (pSi) and a poly (dl-lactide-co-glycolide) acid (PLGA) outer shell. In a murine subcutaneous model, the platform was demonstrated to be fully tunable for the temporal and spatial control release of the payload. Secondly, a multiscale approach was followed in a multicompartment collagen scaffold, to selectively integrate different sets of PLGA-pSi loaded with different reporter proteins. The spatial confinement of the microspheres allowed the release of the reporter proteins in each of the layers of the scaffold. Finally, the staged and zero-order release kinetics enabled the temporal biochemical patterning of the scaffold. The last step of this PhD project was to test if by fully embedding PLGA microspheres in a highly structured and fibrous collagen-based scaffold (camouflaging), it was possible to prevent their early detection and clearance by macrophages. It was further studied whether such a camouflaging strategy was efficient in reducing the production of key inflammatory molecules, while preserving the release kinetics of the payload of the PLGA microspheres. Results demonstrated that the camouflaging allowed for a 10-fold decrease in the number of PLGA microspheres internalized by macrophages, suggesting that the 3D scaffold operated by cloaking the PLGA microspheres. When the production of key inflammatory cytokines induced by the scaffold was assessed, macrophages' response to the PLGA microspheres-integrated scaffolds resulted in a response similar to that observed in the control (not functionalized scaffold) and the release kinetic of a reporter protein was preserved.

Tipologia del documento
Tesi di dottorato
Minardi, Silvia
Dottorato di ricerca
Scuola di dottorato
Scienze chimiche
Settore disciplinare
Settore concorsuale
Parole chiave
tissue engineering; scaffolds; drug delivery.
Data di discussione
29 Aprile 2015

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi