Project Objectives

• Engineer recombinant laminin‑derived protein fragments that replicate the biological functions of native laminin.
• Ensure fragments can be produced at high purity and concentration using animal‑free, scalable in‑vitro systems.
• Enable robust coupling of fragments to synthetic hydrogels (PEG and fibrin‑based).
• Validate the biological activity of fragments in small‑intestinal organoid culture systems.
• Benchmark recombinant fragments against basement membrane extract (BME)‑derived laminin.
• Prepare for broad adoption through Swiss‑wide validation, free sample distribution, and training workshops.

3Rs Impact

• Eliminates the need for tumour‑bearing mice currently used to produce basement membrane extract (BME).
• Reduces global mouse use dramatically, with BME demand estimated at ~300,000 mice per year worldwide.
• Strengthens organoids as an alternative to in‑vivo models by improving matrix definition, reproducibility, and clinical potential.
• Enhances scientific rigour by replacing variable, immunogenic BME with a defined recombinant matrix.
• Facilitates regulatory acceptance of fully animal‑free organoid systems for research and translational applications.

Background

Organoids are three‑dimensional mini‑tissues grown from stem cells, which have transformed biomedical research by providing human‑relevant models for development, disease, and personalised medicine. Their widespread use reduces reliance on animal experiments, yet current organoid cultures depend heavily on basement membrane extract (BME), a gelatinous matrix derived from tumours grown in mice. BME provides critical biochemical cues for organoid formation, but it is poorly defined, highly variable, immunogenic, and incompatible with clinical translation. Its production places a substantial burden on animals, with global BME use estimated to require hundreds of thousands of tumour‑bearing mice every year.

Recent synthetic hydrogels, including PEG‑based and fibrin‑based matrices, offer promising animal‑free alternatives but still require supplements of laminin complexes purified from BME. Replacing this final animal‑derived component remains a critical bottleneck. This project develops recombinant laminin‑like fragments which are engineered to retain biological activity, achieve high purity and concentration, and integrate seamlessly into the synthetic matrices used for organoid culture. By producing functional laminin analogues through fully in‑vitro expression systems, the project aims to eliminate the last dependence on mouse‑derived material, enabling consistent, scalable, and clinically translatable organoid platforms.