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Title: Stiffness memory of 3D-TIPS elastomer nanohybrid scaffolds for biologically responsive bespoke tracheal implants
Author: Wu, Linxiao
ISNI:       0000 0004 7970 6232
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Advancements in materials science and 3D printing have inspired the development of bespoke stimuli responsive scaffolds as an attempt to handle challenging issues in tracheal tissue engineering, especially epithelialization and re-vascularization. Poly(urea-urethane)-polyhedral oligomeric silsequioxane (PUU-POSS) elastomers were selected for their appealing mechanical properties and in vitro responses with several cell lines. However, manufacturing PUU-POSS into 3D tracheal structures using conventional printing techniques remains challenging. In this thesis, a reverse 3D printing technique, based on controlled thermally-induced phase separation (TIPS) (3D-TIPS) of a PUU-POSS nanohybrid polymer solution and microphase separation of soft and hard segments of PUU-POSS, was developed to manufacture a wide range of soft elastomer scaffolds with hierarchically porous structure and tuneable stiffness. The dynamic changes of structure, mechanical properties and cellular responses to those scaffolds in vitro and in vivo were systematically characterized. The thermoresponsive stiffness softening of the scaffold was observed at body temperature, which is near the crystal-to-rubber phase transition of the soft segments of PUU-POSS. A potential application of a synthetic trachea based on the 3D-TIPS scaffolds was demonstrated. A successful submucosal tissue analogue of the trachea has been developed based on the multi-layered co-culture of human bronchial epithelial cells (hBEpiCs), human bronchial fibroblast cell (hBFs) or human bone-marrow derived mesenchymal stem cells (hBM-MSCs) supported by collagen hydrogel impregnated the scaffolds as matrix, reminiscent of the native tracheobronchial epithelium architecture. Furthermore, cellular responses of using human dermal fibroblasts (HDFs) and hBM-MSCs on the scaffolds and rat animal model proved the different roles of the hierarchical porous structure, initial stiffness and stiffness softening in modulating cell growth and differentiation, tissue ingrowth and vascularization. Overall, thermoresponsive biomimetic scaffolds by 3D-TIPS hold promise for personalized and biologically responsive soft tissue implants and implantable device with better mechanical matches, angiogenesis and tissue integration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available