Novel hydrogels: are they poised to transform 3D cell-based assay systems in early drug discovery?

ABSTRACT

Introduction

Success in drug discovery remains unpredictable. However, more predictive and relevant disease models are becoming pivotal to demonstrating the clinical benefits of new drugs earlier in the lengthy drug discovery process. Novel hydrogel scaffolds are being developed to transform the relevance of such 3D cell-based in vitro assay systems.

Areas covered

Most traditional hydrogels are still of unknown composition and suffer significant batch-to-batch variations, which lead to technical constraints. This article looks at how a new generation of novel synthetic hydrogels that are based on self-assembling peptides are poised to transform 3D cell-based assay systems by improving their relevance, reproducibility and scalability.

Expert opinion

The emerging advantages of using these novel hydrogels for human 3D screening assays should enable the discovery of more cost-effective drugs, leading to improved patient benefits. Such a disruptive change could also reduce the considerable time lag from obtaining in vitro assay data to initiating clinical trials. There is now a sufficient body of data available in the literature to enable this ambition to become a reality by significantly improving the predictive validity of 3D cell-based assays in early drug discovery. Novel hydrogels are key to unlocking the full potential of these assay systems.

KEYWORDS:

• 3D culture
• cell culture
• cellular assays
• extracellular matrix
• hydrogels
• organoids
• peptides
• pipeline attrition
• spheroids
• tissue culture

Article highlights

• Translational success in drug discovery has remained unpredictable for decades

• In vitro 3D cellular models of human disease are becoming pivotal to demonstrating the potential downstream clinical benefits of new drugs

• 3D cell-based assay systems typically rely on exogenous hydrogels to mimic the extracellular matrix effectively

• Modern hydrogel developments are now responding to this challenge to improve the quality and relevance of such 3D assays

• Emerging data from recent publications now suggest that significant progress has been made towards using 3D cultures from human biopsies to get the right drug into the right patient

This box summarizes key points contained in the article.

Declaration of interest

JM Treherne is a director and shareholder with Talisman Therapeutics and Cell Guidance Systems. A Miller is a director and shareholder in Manchester BIOGEL. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are funded by Talisman Therapeutics Ltd, Cell Guidance Systems Ltd. They are also supported by the University of Manchester.