Y26 - Injectable ECM-Derived Microgels from Ocular Tissue for Targeted Retinal and Optic Nerve Regeneration

Introduction: : The World Health Organization reports that over 2.2 billion people worldwide suffer from vision impairment, resulting in an estimated $411 billion USD in lost productivity each year. Among the leading causes, damage to the retina and optic nerve remains a major clinical challenge, with few effective regenerative therapies available. Although decellularized scaffolds have enhanced our understanding of native extracellular matrix (ECM) composition, their clinical use is hindered by the need for invasive surgical implantation. This project proposes the development of injectable ECM-derived microgels sourced from porcine retina, cornea, and optic nerve tissues. These microgels are designed to promote localized cell survival, neuroprotection, and tissue regeneration. By enabling minimally invasive delivery of native ECM components and therapeutic agents directly to damaged sites, this approach offers a promising strategy for treating vision loss associated with retinal and optic nerve injuries.

Materials and

Methods: : Fresh porcine ocular tissues have been decellularized utilizing optimized protocols to maintain bioactive extracellular matrix (ECM) components. The resultant ECM matrices were enzymatically digested and crosslinked to fabricate microgels with in situ gelling capabilities suitable for injectable delivery. Proteomic identification and quantification of retained ECM proteins were compared against the Human Eye Proteome Project (EyeOme) catalogue to verify biomimetic fidelity. Comprehensive characterization of microgels, including determination of particle size distribution, mechanical stiffness, and gelation kinetics, will be presented. Furthermore, retinal pigment epithelium (RPE) and retinal ganglion cells (RGCs) will be used to evaluate cell viability, adhesion, proliferation, and neurite extension capacity. Additionally, microgels will be functionalized for controlled release of neurotrophic factors and exosomes, aiming to augment their therapeutic efficacy for retinal regeneration applications.

Results, Conclusions, and Discussions:: The ECM-derived microgels retain critical structural and bioactive components inherent to native ECM, notably laminin, collagen IV, and fibronectin, proteins essential for neural cell adhesion, survival, and functional maintenance. Proteomic characterization will quantify the close alignment between the microgel composition and the established EyeOme profile, indicating biochemical fidelity to healthy ocular tissues. These microgels exhibit advantageous rheological properties, including shear-thinning characteristics and rapid gelation under physiological temperatures, enabling minimally invasive administration through subretinal or peri-optic nerve injections. In vitro analyses using retinal pigment epithelial (RPE) cells and retinal ganglion cells (RGCs) cultured within these ECM-derived microgels provide a microenvironment conducive to homeostasis. Microgels engineered to deliver sustained release profiles will effectively promote neurite extension and initiate neuro-regenerative signaling pathways. This study introduces a biomimetic platform derived from porcine ocular ECM for treating retinal and optic nerve injuries. The injectable microgel format combines native matrix with controlled therapeutic delivery, representing a versatile tool for neuro-regenerative strategies. These findings lay the groundwork for in vivo studies and potential clinical translation in treating degenerative or traumatic vision loss.

Acknowledgements and/or References (Optional)::