A Lindenmayer system-based approach for the design of nutrient delivery networks in tissue constructs

Abstract

Large thick tissue constructs have reported limited success primarily due to the inability of cells to survive deep within the scaffold. Without access to adequate nutrients, cells placed deep within the tissue construct will die out, leading to non-uniform tissue regeneration. Currently, there is a necessity to design nutrient conduit networks within the tissue construct to enable cells to survive in the matrix. However, the design of complex networks within a tissue construct is challenging. In this paper, we present the Lindenmayer system, an elegant fractal-based language algorithm framework, to generate conduit networks in two- and three-dimensional architecture with several degrees of complexity. The conduit network maintains a parent-child relationship between each branch of the network. Several L-system parameters have been studied-branching angle, branch length, ratio of parent to child branch diameter, etc-to simulate several architectures under a given L-system notation. We have also presented a layered manufacturing-based UV-photopolymerization process using the Texas Instruments DLP system to fabricate the branched structures. This preliminary work showcases the applicability of L-system-based construct designs to drive scaffold fabrication systems.

Evaluation of Polyethylene Glycol Diacrylate-Polycaprolactone Scaffolds for Tissue Engineering Applications

“…We have used PEGDA to generate 3D scaffolds in our research [ 7 ]. Several PEGDA hydrogel scaffolds have been developed for the reconstruction of injured hard and soft tissues, although the in vivo performances have not been reported yet [ 8 , 9 ]. The reason for using PEGDA in our research over other materials is that a thin layer of PEGDA membrane can be manufactured readily to allow for cell growth.…”

Biomechanical Performances of Networked Polyethylene Glycol Diacrylate: Effect of Photoinitiator Concentration, Temperature, and Incubation Time

“…Several engineered tissue grafts have been developed for the reconstruction of the injured hard and soft tissues [ 3 ]. Yasar et al [ 4 ] used Lindenmayer systems, an elegant fractal-based language algorithm framework, in designing vasculature networks that could potentially be incorporated in hydrogel scaffolds like PEGDA. The reason for using PEGDA over other materials is that PEGDA is 3D networked structures that can be manufactured easily to allow for the cell growth at higher depth using photolithograph process.…”

“…It has been found to be a valid method to manufacture multiple-layer scaffolds for allowing the constructions of channels within the scaffold to better distribute nutrients to the cells. Yasar et al [ 4 ] study also found that Polyethylene Glycol Diacrylate (PEGDA) tissue scaffolds having thickness higher than 1 mm were shown to have limited applications as a three-dimensional cell culture device due to the inability of cells to survive within the scaffolds. Without access to adequate nutrients, cells placed deep within the PEGDA tissue construct having thickness higher than 1 mm die out, leading to nonuniform tissue regeneration.…”

Automating the Processing Steps for Obtaining Bone Tissue-Engineered Substitutes: From Imaging Tools to Bioreactors

“…The mechanical properties of scaffolds can also be adjusted according to numerically generated models to meet the desired requirements. 18 Porosity patterns can be generated by using design-based methods 19 and/or fabrication-based methods 20 either by simple repetition of predetermined subunits 21 or generated by means of mathematical models developed by analysis of the target tissue structure 22,23 (Fig. 2).…”