Biomimetic Design and Fabrication of Interior Architecture of Tissue Scaffolds Using Solid Freeform Fabrication

Modeling, design and fabrication of tissue scaffolds with intricate architecture, porosity and pore size for desired tissue properties presents a challenge in tissue engineering. This paper will present the details of our development in designing and fabrication of the interior architecture of scaffolds using a novel design approach. The Interior Architecture Design (IAD) approach seeks to generate scaffold layered freeform fabrication tool path without forming complicated 3D CAD scaffold models. This involves: applying the principle of layered manufacturing to determine the scaffold individual layered process planes and layered contour; defining the 2D characteristic patterns of the scaffold building blocks (unit cells) to form the Interior Scaffold Pattern; and the generation of process tool path for freeform fabrication of these scaffolds with the specified interior architecture. Feasibility studies applying the IAD algorithm to example models and the generation of fabrication planning instructions will be presented.Mechanical Engineerin

Implantation of a poly-L-lactide GCSF-functionalized scaffold in a model of chronic myocardial infarction

A previously developed poly-l-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling. These findings were coupled with a reduction in end-systolic and end-diastolic volumes, indicating a preventive effect of the scaffold on ventricular dilation, and an improvement in cardiac performance

Development of a Computational Model for Cell Activity in a Nano-Scaffold

Tissue engineering utilizes nano-scaffolds to direct cell growth and control cell behavior. Since cells occupy specific spaces within extracellular matrix (ECM) it’s important to understand how the geometry of these spaces influence cell behaviors such as movement, death and proliferation. Understanding how the 3-dimensional geometry created by the alignment and density of fibers within the scaffold dictates cell behavior can ultimately lead to scaffold design which promotes more rapid and complete healing. However due to the constraints surrounding bioactive implants and their experimental status there exists little data on how effective nano-scaffolds have performed. The goal of this research is to outline how a computational model can accurately simulate cell behavior within a nano-scaffold to better optimize scaffold parameters. Therefore, this research will examine fiber deposition, degradation, and realignment by cells in a scaffold. Additionally, this research will also cover programmed cell behavior such as movement, death and proliferation. Incorporating this knowledge into scaffold design could aid in the advancement of regenerative medicine and shape the future of tissue engineering

Micro computed tomography based finite element models of calcium phosphate scaffolds for bone tissue engineering

Bone is a living tissue that is able to regenerate by itself. However, when severe bone defects occur, the natural regeneration may be impaired. In these cases, bone graft substitutes can be used to induce the natural healing process. As a scaffold for tissue engineering, these bone graft substitutes have to meet specific requirements. Among others, the material must be biocompatible, biodegradable and have a porous structure to allow vascularization, cell migration and formation of new bone. Additionally, the mechanical properties of the scaffold have to resemble the ones of native tissue. The goal of this project is to create a computational model of the calcium phosphate scaffolds that are produced by rapid-prototyping by the Biomaterials, Biomechanics, and Tissue Engineering group at the Technical University of Catalonia. These models are based on finite element analysis and micro computed tomography images in order to consider the actual architecture of the scaffolds. The generated FE-models allow the computation of both local strains, which act as mechanical stimuli on attached cells, as well as the behaviour of the entire scaffold. When considering this information, the scaffold can be optimized for tissue differentiation by tuning both the scaffold architecture and the scaffold material bulk properties.Incomin

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