Cyclodextrin-Collagen Implants for Corneal Biointegration
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Solution Overview
Problem
Current corneal replacement technologies, such as synthetic keratoprosthesis and bioengineered corneas, face challenges with biointegration and tissue remodeling due to the lack of proteoglycans, which are crucial for collagen organization and transparency, limiting their effectiveness in corneal regeneration.
Innovation Solution
Development of a biomimetic collagen-based matrix using cyclodextrins as proteoglycan substitutes to create a vitrified matrix gel with aligned collagen fibrils, enhancing thermal stability and mechanical properties, and potentially serving as a drug reservoir for corneal repair.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If synthetic polymer-based keratoprosthesis are used, then refractive properties are corrected, but tissue remodeling and biointegration are not supported
Solution Approach 1:
The patent uses a composite material system combining collagen (providing structural framework and biocompatibility) with cyclodextrins (providing proteoglycan-like functions for fibril organization). This composite approach allows the material to simultaneously achieve refractive correction through optical clarity while supporting biointegration through biological compatibility and tissue remodeling capabilities that pure synthetic polymers cannot provide.
2Manufacturing precision
If proteoglycans are added to collagen matrix, then collagen fibril organization and transparency are improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses cyclodextrins as intermediary molecules that mediate between collagen fibrils, mimicking the natural role of proteoglycans. Cyclodextrins act as molecular spacers and organizers that regulate collagen self-assembly into ordered fibrils with appropriate spacing, achieving transparency and structural organization without requiring complex proteoglycan purification and integration processes.
Solution Approach 2:
The patent changes the molecular parameters by introducing cyclodextrins with specific hydroxyl group substitutions that alter the physical-chemical properties of the collagen matrix. These parameter changes in molecular structure and interaction enable controlled fibril spacing and organization, achieving desired optical and mechanical properties through compositional modification rather than complex manufacturing procedures.
3Reliability
If natural cyclodextrins are used, then biocompatibility is achieved, but solubility is poor
Solution Approach 1:
The patent modifies the chemical parameters of cyclodextrins by substituting hydroxyl groups with various functional groups (carboxyl, amino, sulfonate, etc.). These parameter changes in chemical structure dramatically improve water solubility while preserving the core cyclodextrin structure that provides biocompatibility and molecular recognition capabilities for collagen interaction.
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 cyclodextrin-collagen compositions form transparent, mechanically strong membranes that mimic the native cornea's ultrastructure and properties, offering improved optical and mechanical performance for corneal regeneration and drug delivery.
Implementation Method 1
cyclodextrins as such molecules - small cyclic oligosaccharides classified depending on the number of glucose monomers in the ring which were detailed in WO 2015/164733. These have been previously used in cancer therapy and other applications for drug delivery and have been deemed very safe and biocompatible.
Implementation Method 2
The membranes were formed by a three-stage sequence of gelation, vitrification and rehydration.
Data Source
Figure 1A~1B
Figure 2
Figure 3
AI summary
The present inventors employed cyclodextrins for use as a proteoglycan substitute to engineer a biomimetic collagen-based matrix composition. The resulting incorporation of cyclodextrin in the inventive collagen compositions increased collagen thermal stability and reduced collagen fibrogenesis. As a result, a thick, transparent and mechanically strong collagen- based composition was formed. This cyclodextrin-collagen composition holds a great potential to be used as a therapeutic eye patch for corneal repair. Additionally, the composition can support development of multi-layered structures, with different layers promoting different biological properties. Methods for making these inventive compositions and their use are also provided.