DNA microbeads for spatio-temporally controlled morphogen release within organoids

Area of Science:

• Biotechnology
• Developmental Biology
• Tissue Engineering

Background:

• Organoids are valuable in vitro models but often lack full maturity and function due to limited internal biochemical cues.
• Current methods struggle to provide precise, internal biochemical signaling necessary for guided organoid development.

Purpose of the Study:

• To introduce a novel method for delivering spatio-temporally controlled morphogen gradients within organoids.
• To enhance organoid maturity and function by mimicking in vivo developmental signaling.
• To demonstrate the adaptability of this technology for various organoid systems.

Main Methods:

• Nanoengineered DNA microbeads with tunable stiffness were fabricated.
• Microbeads were integrated into medaka retinal organoids and embryos via microinjection.
• Light-induced non-invasive erasure of microbeads was demonstrated.
• Recombinant surrogate Wnt was coupled to DNA microbeads for controlled morphogen release.

Main Results:

• DNA microbeads successfully delivered controlled morphogen gradients within organoids and embryos.
• Spatio-temporally controlled Wnt release induced retinal pigmented epithelium formation.
• Neuroretinal cell types were maintained, leading to improved retinal organoid cell diversity.
• The technology showed potential for adaptation to other organoid systems.

Conclusions:

• The developed DNA microbead technology enables precise control over morphogen gradients in organoids.
• This approach significantly enhances the developmental mimicry and maturity of in vitro organoid models.
• The facile fabrication and non-invasive nature of the microbeads offer broad applicability in regenerative medicine and developmental biology.