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

3D hybrid wound devices for spatiotemporally controlled release kinetics

This paper presents localized and temporal control of releasekinetics over 3-dimensional (3D) hybridwounddevices to improve wound-healing process. Imaging study is performed to extract wound bed geometry in 3D. Non-Uniform Rational B-Splines (NURBS) based surface lofting is applied to generate functionally graded regions. Diffusion-based releasekinetics model is developed to predict time-based release of loaded modifiers for functionally graded regions. Multi-chamber single nozzle solid freeform dispensing system is used to fabricate wounddevices with controlled dispensing concentration. Spatiotemporal control of biological modifiers thus enables a way to achieve target delivery to improve wound healing

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

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

Optimized normal and distance matching for heterogeneous object modeling

This paper presents a new optimization methodology of material blending for heterogeneous object modeling by matching the material governing features for designing a heterogeneous object. The proposed method establishes point-to-point correspondence represented by a set of connecting lines between two material directrices. To blend the material features between the directrices, a heuristic optimization method developed with the objective is to maximize the sum of the inner products of the unit normals at the end points of the connecting lines and minimize the sum of the lengths of connecting lines. The geometric features with material information are matched to generate non-self-intersecting and non-twisted connecting surfaces. By subdividing the connecting lines into equal number of segments, a series of intermediate piecewise curves are generated to represent the material metamorphosis between the governing material features. Alternatively, a dynamic programming approach developed in our earlier work is presented for comparison purposes. Result and computational efficiency of the proposed heuristic method is also compared with earlier techniques in the literature. Computer interface implementation and illustrative examples are also presented in this paper

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

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

Modeling of spatially controlled biomolecules in three-dimensional porous alginate structures

This paper presents a computer-aided design (CAD) of 3D porous tissue scaffolds with spatial control of encapsulated biomolecule distributions. A localized control of encapsulated biomolecule distribution over 3D structures is proposed to control release kinetics spatially for tissue engineering and drug release. Imaging techniques are applied to explore distribution of microspheres over porous structures. Using microspheres in this study represents a framework for modeling the distribution characteristics of encapsulated proteins, growth factors, cells, and drugs. A quantification study is then performed to assure microsphere variation over various structures under imaging analysis. The obtained distribution characteristics are mimicked by the developed stochastic modeling study of microsphere distribution over 3D engineered freeform structures. Based on the stochastic approach, 3D porous structures are modeled and designed in CAD. Modeling of microsphere and encapsulating biomaterial distribution in this work helps develop comprehensive modeling of biomolecule release kinetics for further research. A novel multichamber single nozzle solid freeform fabrication technique is utilized to fabricate sample structures. The presented methods are implemented and illustrative examples are presented in this paper

Multi-directional blending for heterogeneous objects

This paper presents a novel multi-directional blending method for heterogeneous object design. Contrary to earlier studies, this paper introduces material blending through multiple features with different heterogeneous material composition. Feature-based method is used to represent and design heterogeneous objects with multi-directional material composition. The Voronoi diagram of multiple curves is constructed to generate bisector of the geometric domain. Then, metamorphosis from the bounding curve to multiple internal curves is performed using dynamic programming based optimization approach in two steps. First, optimum curve matching between internal curves and enclosing Voronoi cells is obtained. Then, an optimum ruling line alignment and insertion technique between the Voronoi diagram and the bounding curve is developed. Metamorphosis through complex concavities is also achieved. Finally, multi-directional material composition is mapped based on a set of relations

Spatially multi-functional porous tissue scaffold

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 layer consecutively to generate functionally gradient porosity, which follows the geometric shape of the scaffold. The proposed approach constructs the medial region from the medial axis of each corresponding layer. The radial layers of the scaffold are then generated by connecting the boundaries of the medial region and the layer's outer contour. Gradient porosity is changed between the medial region and the layer's outer contour. Iso-porosity regions are determined by dividing the sub-regions peripherally into pore cells and consecutive iso-porosity curves are generated using the iso-points 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. 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