STRUCTURAL DETERMINISTIC MODELING DESIGN AND FABRICATION OF ELECTROSPUN SCAFFOLDS FOR SOFT TISSUE ENGINEERING

The research fields of tissue engineering, biomechanics and regenerative medicine continue to evolve in response to the ever growing need for tissue replacement options. These fields aim to restore, maintain, or improve tissue or whole organ function. This doctoral studies focus on the development and experimental validation of a structural deterministic modeling strategy to: A) guide tissue engineering scaffold design, B) provide a better understanding of cellular mechanical and metabolic response to local micro-structural deformations. Targeted clinical application was the pulmonary heart valve. Electrospinning was selected as the optimal platform technology to implement, validate and test the presented designing strategy. An innovative custom made software was developed and tested on Electrospun poly (ester urethane) urea scaffolds (ES-PEUU), decellularized native tissues and collagen gels to fully characterized engineered constructs morphology. These structural information were adopted to feed and assist the mechanical modeling Two previously unevaluated fabrication modalities were investigated throughout both mechanical testing and image analysis in order to explore further how the electrospinning fabrication process can alter the structure and mechanical response: variation of mandrel translation velocity and concurrent electrospraying of cell culture medium with or without cells or rigid particulates. These fabrication parameters were studied to enrich control in the electrospinning process. 8 The detected material topology and mechanical equi-biaxial data were adopted to generate statistically equivalent scaffold mechanical models. The structural determinist approach was applied to ES-PEUU scaffolds, validated and mechanical response at organ and cell level was produced through FEM simulation. Prediction included: membrane tension vs. stretch relation, elasticity moduli, Nuclear Aspect Ratio vs. stretch relation for the cells micro-integrated into the scaffold. A three weeks in vivo - study on an ovine model was performed to demonstrated the feasibility of the adoption of ES-PEUU for TEHVs and more generally this material potential for soft tissue regeneration. Explants analysis showed surgical feasibility and acceptable valve functionality. The developed design strategies combining image analysis and structural deterministic modeling enabled the material topology to be both quantified and reproduced. Material fabrication parameters were related to material micro-architecture Similarly, the micro-architecture was related to macro scale mechanical responses such as in-plane reactions or flexural rigidity, and complex meso – micro scales mechanisms such NAR – stretch relation. In conclusion, the modeling approach introduced in this work bridges for the first time the scaffold fabrication parameters with the mechanical response at different scale length. The developed paradigm will be utilized to identify the optimal scaffold for a given soft tissue engineering application.