Advancing animal-free organ-on-a-chip models with PeptiMatrix

Tim will assess whether PeptiMatrix™, a commercially available synthetic hydrogel developed with NC3Rs funding, can replace animal-derived matrices in organ-on-a-chip models used to study cancer metastasis to the bone. His team will evaluate chemically-defined hydrogels of different physiologically-relevant stiffnesses to determine their ability to transmit mechanical loading, support bone cell viability and phenotype, and generate biomechanical responses characteristic of bone tissue. Current in vitro models of bone metastasis rely on animal-derived matrices that often lack physiological relevance, and this study will assess the suitability of PeptiMatrix™ as a defined animal-free alternative for these models.  
 

Organ-on-a-chip (OOAC) technology is enabling improved in vitro cancer modelling, offering increased physiological relevance while reducing reliance on animal models (Nolan et al., 2023). To better capture tumour microenvironment complexity, relevant cells are encapsulated within hydrogels that act as synthetic 3D extracellular matrices (ECM). However, despite the predominant use of human cells, there remains a reliance on animal-derived hydrogels.  

Commonly-used materials, such as Matrigel™ and collagen I, inherently lack human-relevance, are poorly defined, subject to batch variability, and exhibit inadequate mechanical properties, including sub-physiological stiffness and limited ability to transmit mechanical loading. Consequently, they fail to reproduce crucial cell-ECM interactions that underpin cancer cell behaviour. These interactions are exemplified in bone metastasis, a major clinical challenge in lung and breast cancer, where the bone microenvironment’s ECM mechanics and composition regulate tumour cell adhesion, survival, and progression (Verbruggen et al., 2024). Our group is currently developing OOAC models of the bone microenvironment to study cancer metastasis but, as with many other groups, are still reliant on animal derived hydrogels.  

There is an urgent need for characterised, animal-free hydrogels with improved mechanical capabilities. This proof-of-concept project will evaluate the feasibility of using PeptiMatrix™, a fully synthetic, tuneable hydrogel platform, as a replacement for animal-derived hydrogels in OOAC systems modelling the bone microenvironment for cancer metastasis studies. Three PeptiMatrix™ formulations, representing physiologically relevant ECM stiffnesses, will be assessed for their ability to (i) transmit mechanical loading, (ii) maintain bone cell viability and phenotype, (iii) drive physiologically relevant biomechanical responses. These will be benchmarked against existing data using collagen I and Matrigel™, in two commercial OOAC platforms, Emulate™ Chip-S1® and BiomimX uBeat®, which enable application of stretch and/or compression.  

The project will demonstrate PeptiMatrix™ suitability in OOAC models and provide a reproducible, 3Rs-aligned hydrogel resource to enhance model fidelity and reduce animal dependence.