Innervated Cornea Model Using Layered Silk Scaffolds
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Solution Overview
Problem
Current corneal tissue models fail to accurately mimic the anatomy and mechanical properties of the human cornea, lacking distinct anatomical layers and functional innervation, which limits their ability to study corneal diseases and drug screening effectively.
Innovation Solution
Development of corneal tissue models that include the stroma, epithelium, and innervation using silk scaffolds to support cellular growth, with a unique air-liquid interface environment, allowing for functional innervation and improved cellular interactions, and the use of growth factors to enhance cellular migration and differentiation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional tissue models are used, then manufacturing is simple, but they fail to mimic corneal anatomy and mechanical properties
Solution Approach 1:
The corneal tissue model is divided into distinct anatomical layers (epithelium, stroma, endothelium) cultured on separate scaffolds that are subsequently assembled. This segmentation allows each layer to be optimized independently while achieving overall anatomical accuracy, resolving the contradiction between manufacturing simplicity and anatomical fidelity.
Solution Approach 2:
Multiple cell layers are nested within a hierarchical scaffold structure where epithelial cells are cultured on one scaffold, stromal cells on another, and endothelial cells on a third, with growth factors and neural elements nested within the matrix. This nested organization achieves complex anatomical structure through systematic layering rather than monolithic construction.
2Reliability
If current tissue models are used, then resource consumption is low, but they lack functional innervation and cellular interactions
Solution Approach 1:
Different regions of the tissue model are populated with specific cell types and growth factors appropriate to each anatomical location. The epithelium receives epithelial growth factor, the stroma receives neural growth factor for innervation, and the endothelium receives appropriate trophic support. This localized differentiation achieves physiological relevance without requiring uniform distribution of all cellular components throughout the entire model.
Solution Approach 2:
Growth factors and signaling molecules are introduced as intermediaries to mediate cellular interactions and neural innervation. These molecular mediators enable complex physiological functions and cell-to-cell communication without requiring direct physical contact between all cellular components, thereby achieving high physiological relevance with controlled material input.
3Manufacturing precision
If complex multi-layer structures are created, then anatomical accuracy improves, but manufacturing difficulty increases
Solution Approach 1:
Each corneal layer is pre-cultured on its own scaffold independently before final assembly. Epithelial cells are grown on the epithelial scaffold, stromal cells on the stromal scaffold, and endothelial cells on the endothelial scaffold in separate culture conditions optimized for each layer. This preliminary separate cultivation simplifies the manufacturing process by avoiding the need to coordinate all cell types simultaneously, while still achieving precise multi-layer structure upon assembly.
Data Source
AI summary
In some embodiments, the present invention provides tissue compositions including a first silk scaffold comprising a plurality of epithelial cells, a second silk scaffold comprising a plurality of stromal cells, and a plurality of neurons. In some embodiments, provided compositions can function as physiologically relevant corneal model systems for, inter alia, testing of therapeutics for corneal disease and/or injury and production of functional corneal tissue (e.g., for transplant, etc). The present invention also provides methods for making and using provided compositions.