Collagen Scaffold Crosslinking for Shape and Swelling Stability
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Solution Overview
Problem
The limitations of additive refractive surgery techniques using lenticules include the scarcity of donor human corneas, immune reactions to non-human sources, fragility of lenticules, and post-operative swelling due to decellularization, which affect the stability and effectiveness of collagen-based scaffolds.
Innovation Solution
Stabilization methods involving water extraction, compression, and controlled rehydration, along with crosslinking, are employed to shape and strengthen collagen scaffolds, enhancing mechanical strength and preventing swelling in aqueous environments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If decellularization is performed to minimize immune reactions, then immune compatibility is improved, but mechanical strength deteriorates and swelling occurs
Solution Approach 1:
The patent applies crosslinking treatment to alter the chemical parameters of the decellularized collagen scaffold, forming covalent bonds between collagen molecules to restore and enhance mechanical strength while maintaining the immunocompatible decellularized state
Solution Approach 2:
The patent creates a composite structure by combining decellularized collagen with crosslinking agents (such as glutaraldehyde, genipin, or riboflavin-based systems), resulting in a material that possesses both the biocompatibility of decellularized tissue and the enhanced mechanical properties of crosslinked networks
2Object-affected harmful factors
If decellularization is performed to minimize immune reactions, then immune compatibility is improved, but dimensional stability deteriorates due to swelling
Solution Approach 1:
Crosslinking modifies the physical-chemical parameters of the collagen scaffold by creating a three-dimensional network structure that restricts water absorption and swelling, thereby stabilizing dimensions while preserving the immunocompatible decellularized state
Solution Approach 2:
The crosslinking treatment is applied as a preliminary stabilization step before implantation, pre-conditioning the scaffold to resist swelling in the aqueous physiological environment and maintain its intended geometric configuration
3Strength
If water extraction and compression are applied to strengthen the scaffold, then mechanical strength is improved, but shape control becomes more difficult
Solution Approach 1:
The scaffold is shaped to the desired geometry before compression and crosslinking treatments, establishing the target configuration in advance. The subsequent strengthening processes are then applied to this pre-formed shape, preserving manufacturing precision while enhancing mechanical properties
Solution Approach 2:
The processing is divided into distinct sequential steps: shaping first, then compression, then crosslinking. This segmentation allows each operation to be optimized independently, with shaping performed on softer tissue before mechanical strengthening, thereby maintaining shape control throughout the process
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 methods improve the mechanical strength and chemical stability of collagen scaffolds, ensuring they maintain shape and optical clarity for effective intrastromal or intracorneal implantation, reducing post-operative swelling and immune reactions.
Implementation Method 1
crosslinking, can be employed to shape the scaffold, mechanically strengthen it, and inhibit its tendency swell in aqueous environments
Implementation Method 2
water extraction and/or compression, (or desiccation and controlled rehydration), as well as crosslinking, can be employed to shape the scaffold, mechanically strengthen it
Implementation Method 3
water extraction and/or compression, (or desiccation and controlled rehydration), as well as crosslinking, can be employed to shape the scaffold
Implementation Method 4
crosslinking can be employed to shape the scaffold, mechanically strengthen it, and inhibit its tendency swell in aqueous environments
Data Source
AI summary
Shape-stabilized collagen scaffolds and methods of obtaining such scaffolds are disclosed. Stroma can be harvested, for example, from human or porcine corneal stroma and shaped during excision or in a separate step after excision. Following shaping (and preferably decellularization), the excised stroma portion is subject to pressure, force or vacuum to reduce fluid content and then irradiated or otherwise treated to induce crosslinking of collagen chains or fibrils. In one embodiment, the scaffold can be compacted by removing some or all of the water from the scaffold, and rehydrating the scaffold in a controlled manner (e.g., in a mold or other confining space) such that the scaffold takes a desired compacted shape; and then crosslinking at least a portion of the scaffold to mechanically strengthen it and inhibit subsequent swelling. Various sources of energy can be employed to induce crosslinking of collagen including, for example, ultraviolet (UV) radiation. The scaffolds can also be selectively densified or patterned. The invention is particularly useful in forming stable lenticules of enhanced stiffness and sufficient optical clarity for intracorneal implantation in additive ocular surgery.