Development of engineered tissue scaffolds with superior control over cell-protein interactions is still very much infancy. Advancing through heterogeneous multifold scaffolds with controlled release fashion enables synchronization of regenerating tissue with the release kinetics of loaded biomolecules. This might be an engineering challenge and promising approach for improved and efficient tissue regeneration. The most critical limitations: the selection of proper protein(s) incorporation, and precise control over concentration gradient and timing should be overcome. Hence, tissue scaffolds need to be fabricated in a way that proteins or growth factors should be incorporated and released in a specific spatial and temporal orientation to mimic the natural tissue regeneration process. Spatial and temporal control over heterogeneous porous tissue scaffolds can be achieved by controlling two important parameters: (ⅰ) internal architecture with enhanced fluid transport, and (ⅱ) distribution of scaffold base material and loaded modifiers. In this research, heterogeneous tissue scaffolds are designed considering both the parameters. Firstly, the three-dimensional porous structures of the scaffold are geometrically partition into functionally uniform porosity regions and controlled spatial micro-architecture has been achieved using a functionally gradient porosity function. The bio-fabrication of the designed internal porous architecture has been performed using a single nozzle bioadditive manufacturing system. The internal architecture scheme is developed to enhance fluid transport with continuous base material deposition Next, the hybrid tissue scaffolds are modeled with varying material characteristics to mediate the release of base material and enclosed biological modifiers are proposed based on tissue engineering requirements. The hybrid scaffolds are fabricated for spatial control of biomolecules and base material to synchronize the release kinetics with tissue regeneration. A pressure-assisted multi-chamber single nozzle bioadditive manufacturing system is used to fabricate hybrid scaffolds.
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