Reversible Boronate Ester Hydrogels for Injectable Tissue Augmentation
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Solution Overview
Problem
Existing hydrogels based on crosslinked glycosaminoglycans, such as hyaluronic acid and chondroitin sulfate, face challenges in injectability and durability due to high crosslinking density, making them difficult to administer and prone to structural integrity issues.
Innovation Solution
The development of hydrogels with reversible boronate ester linkages between glycosaminoglycans, allowing for easier injection and self-healing properties by forming alkoxyboronate ester anions, which break during injection and quickly reform inside the body, providing a malleable and durable gel structure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If high crosslinking density is used in glycosaminoglycan hydrogels, then structural integrity and durability are improved, but injectability deteriorates
Solution Approach 1:
The patent employs dynamic covalent chemistry using boronate ester bonds that can reversibly break and reform. During injection, the bonds break to reduce viscosity and enable flow through needles; after injection, the bonds reform to restore structural integrity. This dynamic behavior resolves the contradiction between needing strength for durability and ease of operation for injectability.
Solution Approach 2:
The patent changes the chemical parameter of crosslinking from permanent covalent bonds to reversible boronate ester bonds. This parameter change allows the hydrogel to transition between a flowable state (when bonds are broken) and a structured state (when bonds are formed), simultaneously achieving injectability and structural integrity.
2Stability of the object's composition
If permanent covalent crosslinking is used, then structural stability is improved, but self-healing capability deteriorates
Solution Approach 1:
The patent uses dynamic covalent bonds (boronate esters) instead of permanent covalent bonds. These bonds can break and reform in response to environmental conditions, enabling the hydrogel to self-heal after damage while maintaining structural stability during normal use. The reversibility of the bonding provides both stability and repair capability.
Solution Approach 2:
The hydrogel system performs self-healing automatically through the reversible nature of boronate ester bonds. When the hydrogel is damaged, the bonds break and then spontaneously reform to restore the network structure without external intervention, enabling the material to repair itself.
3Duration of action of stationary object
If high crosslinking density is used, then duration of action is improved, but ease of injection deteriorates
Solution Approach 1:
The patent employs dynamic covalent bonds that provide temporary weakness during injection (enabling ease of administration) and permanent strength during in vivo residence (ensuring duration of action). The boronate ester bonds reform after injection, maintaining the hydrogel structure for extended periods.
Solution Approach 2:
The hydrogel undergoes a phase transition from a flowable sol state during injection to a gel state after injection. This transition is controlled by the reversible formation of boronate ester bonds, allowing easy injection followed by sustained structural integrity for prolonged duration of action.
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 hydrogels are easier to inject and exhibit self-healing capabilities, maintaining structural integrity and facilitating precise application in medical and cosmetic treatments, such as wrinkle filling and tissue augmentation.
Implementation Method 1
crosslinking said first glycosaminoglycan with said second glycosaminoglycan by forming an alkoxyboronate ester anion linkage between the boronate hemiester of the second glycosaminoglycan with the backbone diol function of said first glycosaminoglycan
Data Source
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AI summary
A new hydrogel made of crosslinked glycosaminoglycans, particularly crosslinked hyaluronic acid, chondroitin or chondroitin sulfate, having reversible linkages using boroxole derivatives leading to new benefits. Glycosaminoglycans that are crosslinked via an alkoxyboronate ester anion formed between a backbone diol function of a first glycosaminoglycan and a boronate hemiester grafted to a second glycosaminoglycan.