Skip to main content
2024 BMES Annual Meeting Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Tissue Engineering

Tissue Engineering - Poster Session E

Poster AA16 - Bioengineered retina-on-a-chip: an in vitro model to feature glymphatic system in brain/retina interplay

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  The discovery of the glymphatic system (GS) shed new light on the understanding of neuropathological processes. Its critical role in removing neurotoxic substances [1], such as β-amyloid, suggests an intriguing investigation of the role of the glymphatic system both in the brain and the eye β-amyloid related pathological mechanisms. Our aim is to present a preliminary model of retina to be hosted in an advanced technological tool to exploit both an innovative brain and retina-on-chip models including the glymphatic system to address its role in β-amyloid-related pathologies such as Alzheimer’s disease and retinal maculopathies.

Materials and

Methods:  We developed a silk fibroin fibre scaffold using electrospinning to mimic the structure of Bruch's membrane, the basement membrane of the retinal pigment epithelium (RPE) [2]. We seeded this artificial membrane with ARPE19, human retinal pigment epithelial cells, to test its compatibility and functionality. Additionally, we used 3D bioprinting to create a sodium alginate-gelatin (SA-G) bio-ink, designed to serve as an in vitro microenvironment for photoreceptors. We evaluated the SA-G bio-ink from both the mechanical and biological viewpoints, using fibroblast cells to ensure that it provided a suitable microenvironment for cells. Finally, to compare the mechanical properties of our engineered layers with the mechanical properties of the retina, we developed and applied a combined experimental and numerical method to retina samples isolated from pig eyes, determining their mechanical properties in vitro.

Results, Conclusions, and Discussions: Our silk fibroin fibre scaffold successfully mimicked the structure and properties of the native Bruch's membrane, with the mechanical properties of the artificial membrane being comparable to those of the native tissue, having an elastic modulus of 6-14 MPa. Moreover, the seeded ARPE19 human retinal pigment epithelial cells demonstrated viability and proliferation on this artificial substrate. The SA-G bioink exhibited stiffness comparable to that obtained from uniaxial elongation and small punch tests on porcine retinal samples. By fine-tuning the material parameters, our experimental-numerical method returned a value of E = 5.5 kPa for our retina samples. Biologically, the bio-ink supported homogeneous cell distribution and sustained cell viability over time.
Our preliminary results represent a significant step towards developing of a 3D printable and biocompatible hydrogel-based RPE model to be hosted in an innovative GS-retina-on-a-chip device, providing a novel tool to address both brain and eye-related physiopathological scenarios.
The findings presented in this study are the starting point for developing an in vitro retina model. This model will be further integrated with photoreceptors, the functional unit of the retina, and retinal neural cells, which literature suggests play a crucial role in the GS of the retina, to better replicate the in vivo situation.
REFERENCES
[1] Iliff JJ et al., (2012), Sci Transl Med, doi: 10.1126/scitranslmed.3003748.
[2] Belgio B et al., (2021), Bioengineering (Basel), doi: 10.3390/bioengineering8020018.

Acknowledgements (Optional):