Unmodified Collagen Bioink Crosslinking for Corneal Sealing
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Solution Overview
Problem
Current collagen-based products for tissue sealing and delivery of agents to biological targets, such as the cornea, face limitations in strength, elasticity, and transparency, with existing methods failing to adequately address advanced corneal injuries and tissue damage due to insufficient biomechanical properties and complex application processes.
Innovation Solution
Development of printable collagen bioinks using unmodified type I collagen that can be photo-crosslinked, allowing for direct application to biological targets, providing structural support, transparency, and the ability to deliver bioactive molecules, while maintaining shape and facilitating cell migration and proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If chemical modification or cross-linking is used to improve collagen robustness, then strength and elasticity improve, but transparency deteriorates and complexity increases
Solution Approach 1:
The patent replaces chemical cross-linking methods with physical cross-linking using ionizing radiation (electron beam or gamma radiation). This substitution eliminates the need for chemical modifiers while achieving equivalent or superior cross-linking density, thereby maintaining transparency and mechanical strength without the haze caused by chemical additives
Solution Approach 2:
The patent optimizes processing parameters including radiation dose (10-100 kGy), collagen concentration (1-20 mg/ml), and pH (4-7) to achieve the desired balance between cross-linking density and transparency. By precisely controlling these parameters, the patent achieves robust mechanical properties while maintaining optical clarity
2Reliability
If traditional sealants are used for corneal repair, then basic sealing is achieved, but advanced healing requirements (pain relief, infection prevention, scar reduction) are not met
Solution Approach 1:
The patent creates a multi-functional collagen matrix that simultaneously provides structural support, pain relief through anesthetic incorporation, infection prevention via antibiotic delivery, and scar reduction through controlled degradation. This single platform replaces multiple separate treatments with one integrated hydrogel system
Solution Approach 2:
The patent embeds multiple therapeutic agents (anesthetics, antibiotics, growth factors) within the collagen hydrogel matrix structure. These nested functional components are released in a controlled manner, allowing the base collagen structure to provide sealing while embedded agents provide additional healing functions
3Manufacturing precision
If unmodified type I collagen is used for bioink, then transparency and biocompatibility improve, but structural integrity and shape maintenance deteriorate
Solution Approach 1:
The patent uses ionizing radiation (electron beam or gamma radiation) to induce cross-linking in unmodified type I collagen, replacing the need for chemical cross-linking agents. This physical cross-linking method maintains the natural transparency and biocompatibility of collagen while providing the necessary structural integrity for 3D printing and tissue support
Solution Approach 2:
The patent creates a composite structure through radiation-induced cross-linking of collagen fibrils, forming a network that combines the natural properties of unmodified collagen (transparency, biocompatibility) with enhanced mechanical strength. The cross-linked network acts as a composite framework that maintains shape while allowing cell infiltration
4Reliability
If current collagen-based products are used, then basic tissue support is provided, but biomechanical properties remain insufficient for ongoing use
Solution Approach 1:
The patent optimizes collagen concentration (1-20 mg/ml), pH (4-7), and radiation dose (10-100 kGy) to achieve the desired biomechanical properties. By precisely controlling these parameters, the patent creates a hydrogel with tensile strength and elasticity sufficient for ongoing tissue support without causing adverse reactions
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 collagen bioinks offer improved structural integrity and transparency, enabling effective sealing and delivery of agents to biological targets, promoting tissue repair and regeneration, and can be used for various biological applications beyond corneal treatment.
Implementation Method 1
The collagen solution is then crosslinked by exposure to light to form a collagen gel.
Data Source
AI summary
The present inventors have developed printable collagen bioinks using unmodified type I collagen with mechanical and structural properties that facilitate application to tissue in a structured form. In particular, the compositions of the present invention may be used to apply collagen gels to tissue (e.g. eye) using two- or three-dimensional (extrusion) bioprinting techniques.