Hollow 3D Retinal Tissue Units for Minimally Invasive Implantation
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Solution Overview
Problem
Current treatments for retinal diseases, such as age-related macular degeneration and retinopathy, face challenges including ineffective drug injections, invasive surgeries, and poor cell differentiation and integration of retinal implants, leading to limited success and significant side effects.
Innovation Solution
Development of hollow three-dimensional retinal tissue units comprising differentiated living human retinal pigment epithelium cells with their basal faces oriented outwards, integrated with an extracellular matrix, allowing correct polarization and minimally invasive implantation at Bruch's membrane, reducing the need for complex surgeries and improving cell survival and functionality.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If membranes or sheets of retinal cells are used for implants, then cell replacement is achieved, but the surgery becomes long and complex requiring specific grafting expertise
Solution Approach 1:
The retinal implant is divided into multiple concentric layers (photoreceptor layer, neural retina layer, RPE layer) that can be independently prepared and then assembled together. This segmentation allows each layer to be optimized separately and simplifies the implantation process as pre-assembled units can be implanted without complex intraoperative assembly procedures.
Solution Approach 2:
The retinal tissue layers are prepared, organized, and assembled into complete implant units before implantation. The photoreceptor cells, neural retina cells, and RPE cells are pre-differentiated and pre-positioned in their correct anatomical relationships in vitro, eliminating the need for complex surgical manipulation and positioning during the actual implantation procedure.
2Reliability
If stem cells are injected intravitreally to replace retinal cells, then cell replacement is attempted, but cell differentiation is not controlled and side effects occur
Solution Approach 1:
Stem cells are pre-differentiated into specific retinal cell types (photoreceptors, neural retina cells, RPE cells) before implantation. The differentiation process is controlled in vitro using specific culture conditions and growth factors, ensuring that cells are ready to perform their intended function immediately upon implantation without requiring uncontrolled differentiation in vivo.
Solution Approach 2:
Different regions of the implant contain different cell types with specific functions positioned according to retinal anatomy. The photoreceptor layer contains light-sensitive cells, the neural retina layer contains signal-processing cells, and the RPE layer contains supportive cells. Each cell type is differentiated and positioned to perform its specific local function, ensuring proper retinal organization and function.
3Quantity of substance
If large numbers of retinal cells are produced for grafting, then sufficient cell material is available, but most cells are not positioned on the implant and are wasted
Solution Approach 1:
The implant is constructed by assembling a precise number of cells into defined layers and structures before implantation. This allows exact control over the number of cells used, matching the cellular content to the specific requirements of the implant design and the patient's needs, thereby minimizing cell waste while ensuring sufficient cell material is available.
Solution Approach 2:
Cells are pre-assembled into organized tissue structures with precise cell numbers and arrangements determined before implantation. This preliminary organization ensures that every cell included in the implant serves a functional purpose, eliminating the waste associated with traditional methods where excess cells are produced but not properly positioned or survive.
4Reliability
If retinal tissue is grafted to replace degenerated cells, then vision restoration is possible, but correct polarization and adhesion at Bruch membrane are difficult to achieve
Solution Approach 1:
The correct polarization of retinal cells (apical-basal orientation) is established during in vitro culture and assembly of the implant layers. Photoreceptor outer segments are oriented toward the RPE layer, and RPE cells are oriented with their apical surfaces facing the photoreceptors and basal surfaces facing Bruch's membrane. This pre-established polarization ensures proper cellular orientation upon implantation without requiring complex surgical manipulation.
Solution Approach 2:
The implant is structured as separate, organized layers with each layer containing cells of specific types in specific orientations. The photoreceptor layer, neural retina layer, and RPE layer are assembled with correct cellular polarization before implantation, ensuring that when the layers are placed together, all cells are correctly oriented relative to each other and to Bruch's membrane, achieving high manufacturing precision.
Data Source
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AI summary
The invention relates to three-dimensional tissue units which are hollow and which comprise, when organised about an internal opening, at least one layer of living human retinal pigment epithelium cells which are differentiated, the basal face of each cell pointing outwards and the apical face pointing towards the internal opening. The invention also relates to these tissue units for use in the treatment of retinopathies, and to a method for preparing these tissue units and an implantation kit.