Fibrin Corneal Cell Patch Without Xenogeneic Feeder Layer
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Solution Overview
Problem
Existing methods for ophthalmic treatments require a nutrient layer composed of xenogeneic fibroblasts, which is not preferred by regulatory bodies, and there is a need for a patch containing corneal limbal cells that can regenerate the corneal epithelium without such a layer.
Innovation Solution
A fibrin patch containing corneal limbal epithelial cells is developed, with a density of 5,000 to 70,000 cells/cm² on a protein substrate, cultured without a nutrient layer, ensuring the presence of at least 10% p63+ and Ki67+ cells, and manufactured through a process involving fibrinogen gelation, drying, rehydration, and cell seeding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a nutrient layer composed of xenogeneic fibroblasts is used, then cell growth and viability are improved, but regulatory compliance and biocompatibility deteriorate
Solution Approach 1:
The invention extracts and removes the problematic nutrient layer composed of xenogeneic fibroblasts from the culture system. Instead, it uses a purified fibrin matrix derived from human blood that provides structural support and growth factors, thereby eliminating xenogeneic rejection risks while maintaining cell viability and regulatory compliance.
Solution Approach 2:
The fibrin matrix serves as an intermediary substance between the corneal limbal epithelial cells and the culture medium. It provides a biocompatible scaffold that delivers essential growth factors and structural support without introducing xenogeneic components, thus mediating cell growth while ensuring safety.
2Object-affected harmful factors
If corneal limbal epithelial cells are cultured on a fibrin substrate without a nutrient layer, then regulatory compliance and biocompatibility are improved, but cell density and growth rate may deteriorate
Solution Approach 1:
The invention optimizes parameters including cell seeding density (5,000 to 70,000 cells/cm²), fibrin matrix composition, and culture conditions to achieve high cell density and growth rate on the biocompatible fibrin substrate without requiring a nutrient layer, thus maintaining both safety and productivity.
3Reliability
If the initial density of corneal limbal epithelial cells is increased to 5,000-70,000 cells/cm², then therapeutic efficacy is improved, but manufacturing complexity increases
Solution Approach 1:
The invention performs preliminary actions by pre-preparing standardized fibrin substrates with optimized physical and chemical properties before cell seeding. This standardization simplifies the manufacturing process while enabling consistent achievement of high cell density (5,000-70,000 cells/cm²) and therapeutic efficacy.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The patch achieves high viability and therapeutic efficacy by providing a suitable growth niche for transplanted cells, accelerating corneal epithelialization and reducing vascularization and opacity, while maintaining phenotypic characteristics of p63+ and Ki67+ cells.
Implementation Method 1
preparing a mixture for producing a protein substrate, wherein the protein is fibrinogen; manufacturing the protein substrate
Implementation Method 2
the protein substrate is dried to a water content of 5-95% by weight on air
Implementation Method 3
the substrate is rehydrated for 30 min to 2 h
Implementation Method 4
applying corneal limbal epithelial cells onto the scaffold; culturing the cells on the scaffold
Data Source
AI summary
The first object of the invention is a fibrin patch containing corneal limbal epithelial cells, characterized in that it contains a protein substrate, which is dried and rehydrated fibrin, a density of corneal limbal epithelial cells on the protein substrate is from 5,000 cells/cm2 to 70,000 cells/cm2, and the protein substrate does not contain a nutrient layer. The invention discloses also the method of the manufacturing of the patch.