High-throughput design of cultured tissue moulds using a biophysical model

TL;DR

This paper introduces a high-throughput biophysical modeling approach to design tissue moulds that promote highly aligned cell growth, aiding tissue engineering applications like regenerative medicine and cultured meat.

Contribution

It presents a novel computational method for optimizing tissue mould designs using a microscopic biophysical model, enabling scalable and targeted tissue organization.

Findings

Elongated moulds with specific tethering strategies produce highly aligned cells.

Tether placement within protrusions or vertices guides cell alignment effectively.

Proof-of-concept demonstrated for scaffold design based on biophysical modeling.

Abstract

The technique presented here identifies tethered mould designs, optimised for growing cultured tissue with very highly-aligned cells. It is based on a microscopic biophysical model for polarised cellular hydrogels. There is an unmet need for tools to assist mould and scaffold designs for the growth of cultured tissues with bespoke cell organisations, that can be used in applications such as regenerative medicine, drug screening and cultured meat. High-throughput biophysical calculations were made for a wide variety of computer-generated moulds, with cell-matrix interactions and tissue-scale forces simulated using a contractile-network dipole-orientation model. Elongated moulds with central broadening and one of the following tethering strategies are found to lead to highly-aligned cells: (1) tethers placed within the bilateral protrusions resulting from an indentation on the short edge, to guide alignment (2) tethers placed within a single vertex to shrink the available space for misalignment. As such, proof-of-concept has been shown for mould and tethered scaffold design based on a recently developed biophysical model. The approach is applicable to a broad range of cell types that align in tissues and is extensible for 3D scaffolds.