Peptide-Based Hydrogels for Cytocompatible Tissue Engineering

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Solution Overview

Problem

Current hydrogel technologies face challenges in creating materials that are simultaneously cytocompatible, biodegradable, and mechanically rigid, while also being easily processable and capable of rapid formation in vitro or in vivo, due to issues with chemical crosslinking toxicity and limited control over peptide epitope distribution and accessibility.

Innovation Solution

Development of novel peptide-based hydrogels that undergo self-assembly in response to environmental stimuli, such as pH, ionic strength, and temperature, allowing for the formation of rigid, porous scaffolds with controlled kinetics and physical characteristics, eliminating the need for exogenous crosslinking agents and enabling in situ gelation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If chemical crosslinks are introduced to achieve mechanical rigidity in hydrogels, then the structural strength is improved, but toxic by-products are generated that are difficult to remove and compromise biocompatibility

Engineering Contradiction:
Improvemechanical rigidityVSAvoidtoxicity from crosslinking by-products
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent removes the harmful chemical crosslinking step entirely by using physical crosslinking through peptide self-assembly. The peptides naturally form crosslinked networks through non-covalent interactions (hydrogen bonding, hydrophobic interactions, pi-pi stacking) without requiring toxic chemical crosslinking agents, thus extracting the harmful element while preserving the desired mechanical rigidity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces chemical crosslinking mechanisms with physical self-assembly mechanisms. Instead of using chemical reactions to form crosslinks, the system utilizes spontaneous peptide folding and aggregation driven by physical forces (hydrogen bonds, hydrophobic effects, electrostatic interactions) to achieve the same structural reinforcement and mechanical rigidity.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If the hydrogel is designed to be highly porous and dilute to allow cell motility and nutrient diffusion, then cell proliferation is improved, but mechanical rigidity is reduced

Engineering Contradiction:
Improvecell motility and nutrient diffusionVSAvoidmechanical rigidity
Core Design Contradiction:
Ease of operationVSStrength

Solution Approach 1:

The patent applies local quality by creating a hierarchical pore structure where nanoscale porosity (from peptide self-assembly) provides mechanical strength through dense molecular packing, while microscale porosity (from phase separation during gelation) provides channels for cell motility and nutrient diffusion. Each scale serves its specific function, resolving the contradiction between rigidity and permeability.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent creates a composite structure combining densely packed peptide nanofibrils (providing mechanical rigidity) with interconnected microscale pores (providing transport pathways). This composite architecture integrates two seemingly opposing features - dense packing for strength and void space for permeability - into a single functional material.

Inventive Principle:
Principle #40Composite materials

3Stability of the object's composition

If the hydrogel is formed with permanent chemical crosslinks to achieve rigidity, then structural stability is improved, but processibility and injectability are lost

Engineering Contradiction:
Improvestructural stabilityVSAvoidprocessibility and injectability
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent introduces dynamic reversibility to the crosslinked network. The peptide crosslinks are formed through reversible non-covalent interactions that can break and reform. This allows the gel to transition between sol and gel states in response to environmental cues (temperature, pH, ionic strength), enabling injection as a liquid followed by in situ gelation, thus achieving both processibility and structural stability.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent utilizes changes in environmental parameters (temperature, pH, ionic strength) to control the sol-gel transition. By adjusting these parameters, the peptide solution can be kept in a liquid state for injection, then transformed into a rigid gel structure in situ, achieving both ease of administration and structural stability without permanent chemical crosslinks.

Inventive Principle:
Principle #35Parameter changes

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 peptide-based hydrogels are cytocompatible, support cell adhesion and proliferation, and can be easily processed, offering potential for tissue engineering and wound healing applications with controlled gelation and reversibility, enhancing their versatility and safety for use in vivo.

Implementation Method 1

Development of novel peptide-based hydrogels that undergo self-assembly in response to environmental stimuli, such as pH, ionic strength, and temperature

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

peptides undergo self-assembly in response to environmental stimuli, such as pH, ionic strength, and temperature

Methodology Applied
Scientific EffectpH-responsive phase transition: Phase Change

Implementation Method 3

allowing for the formation of rigid, porous scaffolds with controlled kinetics and physical characteristics

Methodology Applied
Scientific EffectTemperature-responsive gelation: Gel

Data Source

PatentUS7858585B2Hydrogels and uses thereof
Publication Date: 2010.12.28 UNIVERSITY OF DELAWARE
  • US7858585B2 patent drawing
  • US7858585B2 patent drawing
  • US7858585B2 patent drawing

AI summary

The present invention provides novel hydrogels and methods of making and using such hydrogels. The present invention provides hydrogels that may be formed by the self-assembly of peptides in solution. Such self-assembly may be brought about by a change in one or more characteristics of the solution. Characteristics of the solution that may be changed include pH, ionic strength, temperature, and concentration of one or more specific ions. In addition, hydrogels of the invention may be disassembled by changing one or more characteristic of the hydrogel such as pH, ionic strength, temperature, and concentration of one or more specific ions.