Design of Polymer Scaffolds for Tissue Engineering Applications

Abstract

Agent-based models (ABM) provide a flexible multi-layer platform to incorporate various modeling techniques into a single hybrid model for designing optimal biomaterial scaffolds for angiogenesis in tissue engineering applications. Scaffold geometrical variables are considered as design variables. The growth factor concentration profile is the only process variable considered in the study. The product variables used to illustrate the combined effects of scaffold design variables and process variables on the outcome of angiogenesis include the density and depth of capillary invasion within the scaffold. The scaffold design process and the ABM developed to simulate angiogenesis are described in this paper. The performance of the ABM and vascularization of polymer scaffolds are evaluated by simulation studies. The effects of pore size, pore size distribution, and interconnectivity on total blood vessel length, invasion depth, and the total number of sprouts formed during the vascularization process are reported. The integration of the simulation of angiogenesis with ABMs and scaffold design techniques provide an iterative process for designing optimal scaffold structures. This facilitates faster design of optimized scaffolds with significantly less cost and enables better understanding of the mechanisms of angiogenesis of polymer scaffolds for tissue engineering applications.

Polyhydroxybutyrate-Based Nanocomposites for Bone Tissue Engineering

“…Polymers also allow structural changes to tune the physicochemical properties. Hence, polymerbased nanocomposites are widely used in various tissue engineering applications such as neuro-engineering, bone engineering, and dental engineering [10,11]. Polymers combined with other nanomaterials such as nano-clay have shown more promising results in tissue engineering compared to pristine polymeric materials.…”

Integrated Design Approaches for 3D Printed Tissue Scaffolds: Review and Outlook

“…Property assessment requires computational advancements for exploring complex design trade-offs. There is a need for assessing how scaffold structural properties such as porosity and interconnectivity link to more complex scaffold functionality such as vascularization and nutrient distribution that are currently explored with simulations [41]. There is a need to build on existing optimization approaches by incorporating more relevant phenomena [17], such as assessment of mechanics, angiogenesis, and tissue growth simultaneously while taking care to ensure efficient search strategies.…”

“…Scaffolds are challenging to design due to the numerous properties linked to scaffold functioning and their respective trade-offs. It is common to configure scaffolds based on acceptable property ranges [39,40], since properties are typically simpler to determine than complex biological behaviors such as vascularization that more directly relate to scaffold functioning [41]. Experiments and simulations on complex biological phenomena inform feasible property values, such as scaffolds typically requiring at least 50% porosity for greater void volume for tissue growth.…”

“…After tissue growth and angiogenesis occurs, fluid flow is impeded and nutrients are further distributed by diffusion from blood vessels. Fluid flow models typically use computational fluid dynamics to predict fluid behavior [43,91], while nutrient distribution through blood vessels requires simulating vasculature growth followed by nutrient diffusion [41,76]. Fluid flow also plays a role in predicting the shear stress that stimulates tissue growth [20,92,93].…”

“…In the rule-based approach software agents represent endothelial cells and interact together with their micro-environment that leads to the invasion of blood vessels into the scaffold. The framework allows for investigating homogeneous and heterogeneous scaffold lattices, and has informed the desirable range of scaffold properties suitable for tissue engineering applications [41]. These models provide a numerical evaluation of total blood vessel length, invasion depth, and total number of sprouts formed during angiogenesis that can later inform diffusion of oxygen and nutrients to different locations in the scaffold.…”