Design and 3D Printing of Hierarchical Tissue Engineering Scaffolds Based on Mechanics and Biology Perspectives

Continued scientific research is crucial for developing new biomedical products, such as tissue engineering scaffolds, that are difficult to optimize due to the complexity of interfacing mechanical and biological systems. In this paper, mechanical and biological perspectives are used to propose and implement an approach for designing hierarchical scaffolds that provide structural support in the body as tissue regenerates. Three sequential steps are proposed for defining design needs, generating design alternatives, and fabricating design prototypes. Design needs are determined by considering mechanical and biological performance requirements, experimental procedures, and fabrication constraints. The primary mechanical requirement is a scaffold’s need to maintain structural integrity, while biologically the scaffold should promote cellular growth. Scaffold design alternatives of four topology types are generated by altering design parameters that describe a scaffold’s structure. Trade-offs are revealed for scaffold porosity and surface area properties that are known to influence mechanical and biological scaffold performance. Scaffolds of each topology type are designed with 80% porosity and fabricated, which enables their potential use in scientific experiments to measure how property trade-offs influence scaffold performance. On the basis of currently available knowledge, a to-scale spinal scaffold implant is designed and fabricated with a graphically maximized surface area to porosity ratio for a hierarchical scaffold, which represents a potentially high performing design from both mechanical and biological perspectives. These results demonstrate the importance of multidisciplinary approaches for designing complex biomedical tissue scaffolds that could significantly improve healthcare through the development of new clinical products. 1.0 INTRODUCTION The translation of scientific findings into engineered designs is challenging, and is a major barrier for developing mechanical products that interface with biological systems [1, 2]. These barriers stem from the inherent complexity of biological systems [3-6], which makes them difficult for engineers to understand and model throughout the design process. Overcoming these barriers can open new doors for healthcare technologies that interface with the human body, with applications including improved drug delivery [7], medical diagnostics [8], and tissue engineering [9]. Unfortunately, a large number of designed products never reach the market due to failing clinical trial stages required for product approval [10-12]. These trials are typically the first time a product is tested in its intended environment of final use, which is typically more complex than experimental tests and computational models consider. These failings reflect a disconnect in how a product is anticipated to perform to how it actually performs. Such disconnects are attributable, in part, to a lack of multidisciplinary design approaches that characterize salient mechanical and biological phenomenon that influence a product’s performance. Testing, modeling, and optimizing a product from mechanical and biological perspectives in isolation is not sufficient, since many biological systems behave differently when depending on their mechanical interactions with other systems and their environment [13, 14]. In this paper, we address a subset of these challenges with a design approach that considers mechanical and biological perspectives for improved research and development of tissue engineering scaffolds. Tissue engineering scaffolds are structures implanted in the human body that provide mechanical support as new tissue grows [9]. Scaffolds can form the basis of clinical products, such as the implantation of a scaffold between two spinal vertebrae to support bone growth after an intervertebral disc is surgically removed [15, 16]. From a mechanical perspective, the implanted scaffold must structurally bear load previously supported by an intervertebral disc. From a biological perspective, the scaffold should facilitate bone growth that successfully fuses the two surrounding vertebrae. Mechanical and biological perspectives are coupled when considering the need for the biocompatiable scaffolds that degrade over time, which causes a decrease in a scaffold’s strength that must be supplemented by the growing tissue [17]. Additionally, the distribution of mechanical loads throughout a scaffold can influence the structural properties of formed bone tissue [18, 19].