Self-assembling Pentapeptide Hydrogels for Cell Protection
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Solution Overview
Problem
Current biomaterials for tissue engineering lack the ability to mimic the dynamic and adaptable nature of the native extracellular matrix, and few self-assembling oligopeptides are available that can form biocompatible three-dimensional scaffolds for cell delivery and tissue regeneration, especially those that are simple to synthesize and can withstand the stresses of injection without damaging cells.
Innovation Solution
Development of novel self-assembling pentapeptides that form robust nanofiber hydrogels under physiological conditions, which are shear-thinning and rapidly self-healing, allowing for the protection of cells during injection and providing a suitable microenvironment for tissue engineering and regenerative medicine applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional biomaterials are used for tissue engineering, then structural support is provided, but they cannot mimic the dynamic and adaptable nature of the native extracellular matrix
Solution Approach 1:
The patent employs self-assembling peptides that dynamically reconfigure their supramolecular structures in response to mechanical stress and environmental cues. The peptide hydrogels exhibit adaptive remodeling where the nanofiber network can reorganize to maintain structural integrity while mimicking the dynamic properties of native ECM, resolving the contradiction between adaptability and structural support.
Solution Approach 2:
The patent utilizes pH-responsive self-assembly of peptides to control hydrogel formation and structural properties. By changing pH parameters, the peptides transition between dissolved and self-assembled states, enabling the material to adapt its structural characteristics to match the dynamic environment of native tissue while maintaining reliable support capabilities.
2Reliability
If self-assembling oligopeptides are used to form three-dimensional scaffolds, then cell viability is improved, but synthesis complexity and cost increase
Solution Approach 1:
The patent divides the peptide structure into modular pentapeptide units with specific functional sequences (e.g., KYFIL, AYFIL). These segmented designs simplify synthesis compared to full-length proteins while maintaining the ability to form biocompatible three-dimensional scaffolds that support cell viability through controlled self-assembly.
Solution Approach 2:
The patent employs short pentapeptide sequences that can be synthesized cost-effectively using standard peptide synthesis methods. These short peptides form transient but functional supramolecular structures that provide necessary biological activity and scaffold formation without requiring expensive, complex material synthesis processes.
3Ease of operation
If injectable hydrogels are used for cell delivery, then cell transplantation is enabled, but mechanical stress during injection damages cells
Solution Approach 1:
The patent designs peptides that self-assemble into hydrogels with dynamic rheological properties. The hydrogel exhibits shear-thinning behavior during injection, allowing it to flow through needles without generating excessive mechanical stress on cells. Upon injection, the hydrogel rapidly self-assembles to provide structural support while protecting encapsulated cells from mechanical damage.
Solution Approach 2:
The patent incorporates the peptide sequences and hydrogel formation mechanism as a protective cushioning system. The hydrogel matrix forms around and protects cells before they are subjected to full mechanical stress during injection, absorbing and distributing forces to prevent cell damage while enabling successful cell delivery.
4Ease of operation
If peptide hydrogels are designed to be shear-thinning for injectability, then cell delivery is improved, but structural stability during application may be compromised
Solution Approach 1:
The patent employs peptides with dynamic self-assembly characteristics that allow the hydrogel to transition between a fluid-like state during injection and a stable gel state during application. The supramolecular structure rapidly reconfigures in response to shear stress, providing injectability while maintaining structural stability through continuous self-assembly and remodeling of the peptide network.
Solution Approach 2:
The patent utilizes phase transition behavior of the peptide hydrogel, transitioning from a disordered liquid state during injection to an ordered gel state during application. This phase change is driven by pH-induced self-assembly of peptides, enabling the material to flow for easy injection then stabilize to provide structural support, resolving the contradiction between injectability and structural stability.
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 pentapeptide hydrogels, known as RAPID hydrogels, effectively protect cells from mechanical stress during injection and provide a biocompatible scaffold for tissue engineering, supporting cell viability and proliferation, while being cost-effective and simple to synthesize.
Implementation Method 1
The instantly-disclosed pentapeptides and peptides containing such self-assembling pentapeptides self-assemble under physiological conditions (e.g., in a physiological buffer under biologically acceptable conditions (e.g., pH of about 6-11, including pH≈7.4)) into long fibrils with sequence-dependent fibrillary morphologies.
Implementation Method 2
These hydrogels are shear thinning hydrogels that have high storage moduli and high rates of recovery after destruction.
Implementation Method 3
These hydrogels are shear thinning hydrogels that have high storage moduli and high rates of recovery after destruction.
Data Source
AI summary
Novel self-assembling pentapeptides and peptides containing such self-assembling pentapeptides, self-assembled hydrogels, and methods of making and using the same are described. These pentapeptides, and peptides containing such pentapeptides, self-assemble under physiological conditions (e.g., in a physiological buffer under biologically acceptable conditions (e.g., pH≈6-11)) into long fibrils with sequence-dependent fibrillary morphologies. The hydrogels comprise one or more these pentapeptides which make up the 3-dimensional nanofibrous network of the hydrogel structure. The hydrogels are shear-thinning hydrogels that have high storage moduli and high rates of recovery after destruction. These hydrogels are useful in various applications, including but not limited to, scaffolds for tissue engineering, 2-dimensional (2-D) and 3-dimensional (3-D) cell cultures, drug delivery and encapsulation of therapeutic agents (cells, molecules, drugs, compounds), injectables (including those that gel in situ, such as hemostatic compositions), hemostatic agents, wound dressings, pharmaceutical carriers or vehicles, cell transplantation, cell storage, virus culture, and virus storage.