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

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

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

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

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

3D bioprinting for reconstituting the cancer microenvironment.

The cancer microenvironment is known for its complexity, both in its content as well as its dynamic nature, which is difficult to study using two-dimensional (2D) cell culture models. Several advances in tissue engineering have allowed more physiologically relevant three-dimensional (3D) in vitro cancer models, such as spheroid cultures, biopolymer scaffolds, and cancer-on-a-chip devices. Although these models serve as powerful tools for dissecting the roles of various biochemical and biophysical cues in carcinoma initiation and progression, they lack the ability to control the organization of multiple cell types in a complex dynamic 3D architecture. By virtue of its ability to precisely define perfusable networks and position of various cell types in a high-throughput manner, 3D bioprinting has the potential to more closely recapitulate the cancer microenvironment, relative to current methods. In this review, we discuss the applications of 3D bioprinting in mimicking cancer microenvironment, their use in immunotherapy as prescreening tools, and overview of current bioprinted cancer models

High-throughput bioprinting of the nasal epithelium using patient-derived nasal epithelial cells.

Progenitor human nasal epithelial cells (hNECs) are an essential cell source for the reconstruction of the respiratory pseudostratified columnar epithelium composed of multiple cell types in the context of infection studies and disease modeling. Hitherto, manual seeding has been the dominant method for creating nasal epithelial tissue models through biofabrication. However, this approach has limitations in terms of achieving the intricate three-dimensional (3D) structure of the natural nasal epithelium. 3D bioprinting has been utilized to reconstruct various epithelial tissue models, such as cutaneous, intestinal, alveolar, and bronchial epithelium, but there has been no attempt to use of 3D bioprinting technologies for reconstruction of the nasal epithelium. In this study, for the first time, we demonstrate the reconstruction of the nasal epithelium with the use of primary hNECs deposited on Transwell inserts via droplet-based bioprinting (DBB), which enabled high-throughput fabrication of the nasal epithelium in Transwell inserts of 24-well plates. DBB of progenitor hNECs ranging from one-tenth to one-half of the cell seeding density employed during the conventional cell seeding approach enabled a high degree of differentiation with the presence of cilia and tight-junctions over a 4 weeks air-liquid interface culture. Single cell RNA sequencing of these cultures identified five major epithelial cells populations, including basal, suprabasal, goblet, club, and ciliated cells. These cultures recapitulated the pseudostratified columnar epithelial architecture present in the native nasal epithelium and were permissive to respiratory virus infection. These results denote the potential of 3D bioprinting for high-throughput fabrication of nasal epithelial tissue models not only for infection studies but also for other purposes, such as disease modeling, immunological studies, and drug screening

The bioprinting roadmap

This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field