Covalently Linked Polypeptide Hydrogels for Wound Healing

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Solution Overview

Problem

There is a need for effective methods to chemically link polypeptides to hydrogels to create mechanically stable compositions that can deliver drugs or biologically-active agents, while also providing specific surface properties and bioactive functions.

Innovation Solution

The development of an acrylate polymeric scaffold covalently linked to polypeptides, such as cytokines, growth factors, or antibodies, using linkers like polyethylene glycol (PEG) or amino acid sequences, which are incorporated into hydrogels to form stable and functional wound dressings or drug delivery systems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If polypeptides are incorporated into hydrogels to provide surface properties and bioactive functions, then the functional performance is improved, but the mechanical stability deteriorates

Engineering Contradiction:
Improvebioactive functionVSAvoidmechanical stability
Core Design Contradiction:
Adaptability or versatilityVSStrength

Solution Approach 1:

The patent creates a composite hydrogel system combining polymeric scaffold with covalently-linked polypeptides. The polymeric scaffold provides mechanical stability while the covalently attached polypeptides (such as RGD peptides) provide bioactive functions. This composite approach allows both requirements to be satisfied simultaneously through the synergistic combination of different material components.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent uses covalent bonding as an intermediary mechanism to link polypeptides to the hydrogel scaffold. This chemical linkage acts as a mediator that firmly attaches the bioactive polypeptides to the structural scaffold, ensuring they remain positioned to interact with cells while maintaining the overall mechanical integrity of the hydrogel structure.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If polypeptides are chemically linked to hydrogels to improve mechanical stability, then the structural integrity is improved, but the complexity of synthesis increases

Engineering Contradiction:
Improvestructural integrityVSAvoidsynthesis complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent incorporates polypeptides with pre-formed reactive groups (such as C-terminal cysteine or N-terminal vinyl groups) that are designed to react with complementary groups on the polymeric scaffold. This preliminary preparation of reactive functionality allows for streamlined covalent coupling during hydrogel formation, reducing the need for multiple separate synthesis steps and simplifying the overall process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent utilizes changes in chemical reactivity parameters during synthesis. By selecting polypeptides with specific reactive terminal groups and matching them with complementary functional groups on the polymer scaffold, the covalent linkage forms under controlled chemical conditions. This parameter-based approach allows for efficient coupling reactions that reduce synthesis complexity while ensuring stable structural integration.

Inventive Principle:
Principle #35Parameter changes

3Strength

If covalent linking of polypeptides to polymeric scaffold is implemented, then the mechanical stability is improved, but the manufacturing process becomes more difficult

Engineering Contradiction:
Improvemechanical stabilityVSAvoidmanufacturing ease
Core Design Contradiction:
StrengthVSEase of manufacture

Solution Approach 1:

The patent merges the polypeptide attachment process with the hydrogel formation process itself. The covalent linking of polypeptides to the polymeric scaffold occurs during the polymerization or crosslinking stage, combining two operations (polypeptide attachment and hydrogel formation) into a single integrated manufacturing step. This eliminates the need for separate attachment procedures, simplifying the overall manufacturing process while ensuring mechanical stability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent designs the system so that the polypeptides and polymeric scaffold self-assemble through covalent bonding during hydrogel formation. The reactive groups on both components are positioned to spontaneously react under the polymerization conditions, allowing the system to self-link without requiring complex external intervention or multi-step processing. This self-service approach reduces manufacturing difficulty while achieving stable covalent integration.

Inventive Principle:
Principle #25Self-service

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 resulting hydrogels are mechanically stable, biocompatible, and capable of controlled release of bioactive agents, promoting healing and tissue reconstruction by interacting with cell surface receptors, and can be used in various applications including wound dressings and tissue engineering.

Implementation Method 1

The acrylate polymeric scaffold is covalently linked to the compound represented by formula (II) at the vinyl group on the C-terminal cysteinyl amide

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

Hydrogels consist of a three-dimensional, polymeric network that holds a liquid medium and retains it through surface tension effects

Methodology Applied
Scientific EffectSurface tension: Surface Tension

Data Source

PatentUS9155796B2Hydrogels with covalently linked polypeptides
Publication Date: 2015.10.13 SUSAVION BIOSCIENCES INC
  • US9155796B2 patent drawing
  • US9155796B2 patent drawing
  • US9155796B2 patent drawing

AI summary

The present invention provides methods of synthesizing hydrogels that contain covalently linked polypeptides. These polypeptides may be tetravalent peptides or polypeptides that bind to cell surface receptors. The hydrogels synthesized by the methods of the present invention may be used in wound dressings or applied directly to wounds to promote healing.