This study demonstrates that combining a fully defined, animal origin-free culture medium with a physiologically relevant extracellular matrix is key to generating clinically compliant RPE cells.

By using a Biolaminin 111–functionalized Biosilk scaffold, the system produces organoids with stable cell-type composition, reliable dopaminergic neuron differentiation, increased functionality, and uniform maturation across the whole 3D tissue, including the core.

Biosilk and Biolaminin 521 enabled centimeter-scale, channel-permeated 3D cultures that differentiated uniformly into neuroectoderm followed by further differentiation into neural subtypes. The neural progenitors retained self-organization, forming ventricle-like zones, and calcium imaging demonstrated spontaneous activity, indicative of functional neuronal network formation.

Biosilk brings 3D culture closer to native tissue biology by providing an ECM-like microfiber architecture that supports firm cell attachment, spreading, focal adhesion formation, and mechanical sensing—features that hydrogels fail to replicate faithfully.

Brain organoids are valuable for modeling human brain development and disease but often lack the complex extracellular matrix (ECM) cues needed for proper cell differentiation and balanced inflammatory signaling. While decellularized porcine brain ECM (P-BdECM) provides a biologically relevant scaffold, the decellularization process depletes some of its native ECM proteins, leading to incomplete support for neuronal and glial maturation.