Functionally heterogeneous porous scaffold design for tissue engineering

Most of the current tissue scaffolds are mainly designed with homogeneous porosity which does not represent the spatial heterogeneity found in actual tissues. Therefore engineering a realistic tissue scaffolds with properly graded properties to facilitate the mimicry of the complex elegance of native tissues are critical for the successful tissue regeneration. In this work, novel bio-mimetic heterogeneous porous scaffolds have been modeled. First, the geometry of the scaffold is extracted along with its internal regional heterogeneity. Then the model has been discretized with planner slices suitable for layer based fabrication. An optimum filament deposition angle has been determined for each slice based on the contour geometry and the internal heterogeneity. The internal region has been discritized considering the homogeneity factor along the deposition direction. Finally, an area weight based approach has been used to generate the spatial porosity function that determines the filament deposition location for desired biomimetic porosity. The proposed methodology has been implemented and illustrative examples are provided. The effective porosity has been compared between the proposed design and the conventional homogeneous scaffolds. The result shows a significant error reduction towards achieving the biomimetic porosity in the scaffold design and provides better control over the desired porosity level. Moreover, sample designed structures have also been fabricated with a NC motion controlled micro-nozzle biomaterial deposition system

Bioadditive manufacturing of hybrid tissue scaffolds for controlled release kinetics

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

Designing heterogeneous porous tissue scaffolds for additive manufacturing processes

A novel tissue scaffold design technique has been proposed with controllable heterogeneous architecture design suitable for additive manufacturing processes. The proposed layer-based design uses a bi-layer pattern of radial and spiral layers consecutively to generate functionally gradient porosity, which follows the geometry of the scaffold. The proposed approach constructs the medial region from the medial axis of each corresponding layer, which represents the geometric internal feature or the spine. The radial layers of the scaffold are then generated by connecting the boundaries of the medial region and the layer's outer contour. To avoid the twisting of the internal channels, reorientation and relaxation techniques are introduced to establish the point matching of ruling lines. An optimization algorithm is developed to construct sub-regions from these ruling lines. Gradient porosity is changed between the medial region and the layer's outer contour. Iso-porosity regions are determined by dividing the subregions peripherally into pore cells and consecutive iso-porosity curves are generated using the isopoints from those pore cells. The combination of consecutive layers generates the pore cells with desired pore sizes. To ensure the fabrication of the designed scaffolds, the generated contours are optimized for a continuous, interconnected, and smooth deposition path-planning. A continuous zig-zag pattern deposition path crossing through the medial region is used for the initial layer and a biarc fitted isoporosity curve is generated for the consecutive layer with C-1 continuity. The proposed methodologies can generate the structure with gradient (linear or non-linear), variational or constant porosity that can provide localized control of variational porosity along the scaffold architecture. The designed porous structures can be fabricated using additive manufacturing processes

Functionally gradient tissue scaffold design and deposition path planning for bio-additive processes

A layer-based tissue scaffold is designed with heterogeneous internal architecture. The proposed layer-based design uses a bi-layer pattern of radial and spiral layer consecutively to generate functionally gradient porosity following the geometry of the scaffold. Medial region is constructed from medial axis and used as an internal geometric feature for each layer. The radial layers are generated with sub-region channels by connecting the boundaries of the medial region and the layer’s outer contour. Proper connections with allowable geometric properties are ensured by applying optimization algorithms. Iso-porosity regions are determined by dividing the sub-regions into pore cells. The combination of consecutive layers generates the pore cells with desired pore sizes. To ensure the fabrication of the designed scaffolds, both contours have been optimized for a continuous, interconnected, and smooth deposition path-planning. The proposed methodologies can generate the structure with gradient (linear or non-linear), variational or constant porosity that can provide localized control of variational porosity along the scaffold architecture. The designed porous structures can be fabricated using bio-additive fabrication processes

Modeling of multifunctional porous tissue scaffolds with continuous deposition path plan

A novel modeling technique for porous tissue scaffolds with targeting the functionally gradient variational porosity with continuous material deposition planning has been proposed. To vary the porosity of the designed scaffold functionally, medial axis transformation is used. The medial axis of each layers of the scaffold is calculated and used as an internal feature. The medial axis is then used connected to the outer contour using an optimum matching. The desired pore size and hence the porosity have been achieved by discretizing the sub-regions along its peripheral direction based on the pore size while meeting the tissue scaffold design constraints. This would ensure the truly porous nature of the structure in every direction as well as controllable porosity with interconnected pores. Thus the desired controlled variational porosity along the scaffold architecture has been achieved with the combination of two geometrically oriented consecutive layers. A continuous, interconnected and optimized tool-path has been generated for successive layers for additive-manufacturing or solid free form fabrication process. The proposed methodology has been computationally implemented with illustrative examples. Furthermore, the designed example scaffolds with the desired pore size and porosity has been fabricated with an extrusion based bio-fabrication process

Multi-function based modeling of 3D heterogeneous wound scaffolds for improved wound healing

This paper presents a new multi-function based modeling of 3D heterogeneous porous wound scaffolds to improve wound healing process for complex deep acute or chronic wounds. An imaging-based approach is developed to extract 3D wound geometry and recognize wound features. Linear healing fashion of the wound margin towards the wound center is mimicked. Blending process is thus applied to the extracted geometry to partition the scaffold into a number of uniformly gradient healing regions. Computer models of 3D engineered porous wound scaffolds are then developed for solid freeform modeling and fabrication. Spatial variation over biomaterial and loaded bio-molecule concentration is developed based on wound healing requirements. Release of bio-molecules over the uniform healing regions is controlled by varying their amount and entrapping biomaterial concentration. Thus, localized controlled release is developed to improve wound healing. A prototype multi-syringe single nozzle deposition system is used to fabricate a sample scaffold. Proposed methodology is implemented and illustrative examples are presented in this paper

Designing bio-mimetic variational porosity for tissue scaffolds

Reconstructing or repairing the damaged or diseased tissues with porous scaffolds to restore the mechanical, biological and chemical functions is one of the major tissue engineering strategies. Development of Solid Free Form (SFF) techniques and improvement in biomaterial properties by synergy have provided the leverage to fabricate controlled and interconnected porous scaffold structures. But homogeneous scaffolds with regular porosity do not provide all the biological and mechanical requirements of an ideal tissue scaffold. Thus achieving controllable, continuous, interconnected gradient porosity with reproducible and fabricatable design is critical for successful regeneration of the replaced tissue. In this research, a novel scaffold modeling approach has been proposed to achieve bio-mimetic tissue scaffolds. Firstly, the optimum filament deposition angle has been determined based on the internal heterogeneous regions and their locations. Then an area-weight based approach has been applied to generate the spatial porosity function to determine the filament deposition location for the desired bio-mimetic porosity. The proposed methodology has been implemented using computer simulation. A micro-nozzle biomaterial deposition system driven by NC motion control has been used to fabricate a sample designed structure

Procedural function-based modelling of volumetric microstructures

We propose a new approach to modelling heterogeneous objects containing internal volumetric structures with size of details orders of magnitude smaller than the overall size of the object. The proposed function-based procedural representation provides compact, precise, and arbitrarily parameterised models of coherent microstructures, which can undergo blending, deformations, and other geometric operations, and can be directly rendered and fabricated without generating any auxiliary representations (such as polygonal meshes and voxel arrays). In particular, modelling of regular lattices and cellular microstructures as well as irregular porous media is discussed and illustrated. We also present a method to estimate parameters of the given model by fitting it to microstructure data obtained with magnetic resonance imaging and other measurements of natural and artificial objects. Examples of rendering and digital fabrication of microstructure models are presented

A continues multi-material toolpath planning for tissue scaffolds with hollowed features

This paper presents a new multi-material based toolpath planning methodology for porous tissue scaffolds with multiple hollowed features. Ruled surface with hollowed features generated in our earlier work is used to develop toolpath planning. Ruling lines are reoriented to enable continuous and uniform size multi-material printing through them in two steps. Firstly, all ruling lines are matched and connected to eliminate start and stops during printing. Then, regions with high number of ruling lines are relaxed using a relaxation technique to eliminate over deposition. A novel layer-by-layer deposition process is progressed in two consecutive layers: The first layer with hollow shape based zigzag pattern and the next layer with spiral pattern deposition. Heterogeneous material properties are mapped based on the parametric distances from the hollow features