Dopamine-Functionalized Cryogel for Wet Tissue Adhesion
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Solution Overview
Problem
Existing biomaterial-based adhesives for surgical procedures face challenges such as poor tissue integration, biomechanical integration, and toxicity, with gelatin-based adhesives degrading rapidly and causing immunological cytotoxicity, fibrin adhesives having weak adhesion and allergenic risks, and cyanoacrylate adhesives being highly toxic. There is a need for a minimally invasive, robust, and biocompatible wet-tissue adhesive for tissue regeneration.
Innovation Solution
Development of a cryogel comprising a bioadhesive molecule, such as dopamine, covalently linked with a polymerizable moiety, specifically an acrylic acid moiety, which is functionalized to prevent oxidation and enhance adhesion, forming a hydrophilic, injectable, and shape-memory material that can be used for tissue repair and regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If gelatin-based adhesives are used, then robust mechanical properties and biocompatibility are achieved, but poor adhesion to native tissues and rapid degradation leading to immunological cytotoxicity occur
Solution Approach 1:
The patent combines gelatin with dopamine functional groups to create a composite adhesive material that leverages the mechanical properties and biocompatibility of gelatin while adding the adhesive capabilities of dopamine to native tissues, thereby resolving the contradiction between mechanical strength and tissue adhesion
Solution Approach 2:
The patent introduces dopamine functional groups at specific locations within the gelatin structure to enhance adhesion to native tissues without compromising the overall mechanical properties and biocompatibility of the gelatin-based adhesive
2Reliability
If fibrin adhesives are used, then biocompatibility is achieved, but poor adhesion, weak tensile strength, and allergenic risks occur
Solution Approach 1:
The patent creates a composite material by integrating dopamine functional groups into the fibrin structure, thereby enhancing adhesion and tensile strength while preserving the biocompatibility of fibrin
Solution Approach 2:
The patent modifies the chemical structure of fibrin by adding dopamine functional groups, changing the material parameters to improve adhesion and tensile strength while maintaining biocompatibility
3Speed
If cyanoacrylate-based adhesives are used, then fast crosslinking and robust bond strengths are achieved, but high toxicity and formaldehyde generation occur
Solution Approach 1:
The patent changes the chemical composition of the adhesive by incorporating dopamine functional groups, which enable fast crosslinking similar to cyanoacrylate but without the associated toxicity and formaldehyde generation, thereby resolving the contradiction between crosslinking speed and toxicity
4Reliability
If DOPA is incorporated to improve adhesion, then wet-surface adhesion is enhanced, but susceptibility to oxidation increases
Solution Approach 1:
The patent introduces antioxidants as intermediary substances that protect the DOPA functional groups from oxidation, thereby maintaining the adhesion-enhancing properties of DOPA while preventing its degradation through oxidation
5Volume of stationary object
If hydrogels undergo crosslinking at subzero temperatures to achieve larger pore size, then cellular infiltration is facilitated, but mechanical strength is reduced
Solution Approach 1:
The patent creates a composite cryogel structure that combines the porous network formed during subzero crosslinking with reinforcing elements that maintain mechanical strength, thereby achieving both large pore sizes for cellular infiltration and adequate mechanical properties
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 cryogel achieves improved wet-tissue adhesion, biocompatibility, and tissue integration, reducing the need for invasive procedures and promoting efficient tissue regeneration with minimal cytotoxicity and immunological complications, outperforming commercial biomaterials in adhesion strength and stability.
Implementation Method 1
Hydrogels undergo crosslinking at subzero temperatures. This process is referred to as cryogelation.
Implementation Method 2
DOPA and PDA have been shown to adhere to both organic and inorganic surfaces and have been incorporated into a variety of polymers including gelatin and hyaluronic acid.
Data Source
AI summary
Disclosed herein are functionalized dopamine derivatives comprising an optionally substituted acrylic acid moiety and optionally a polyethylene glycol linking moiety. The functionalized dopamine derivatives are useful in cryogel formulations to improve the adhesivity of the cryogel, while preventing undesirable oxidation typically associated with dopamine-containing hydrogels and cryogels. Properties such as cryogel adhesivity, pore size, and interconnectivity are tunable features. Also provided herein are methods of treating a wound or promoting tissue regeneration with a cryogel of the invention or a formulation comprising such a cryogel.