Cyclic Peptide Ligand Scaffolds for Vascularized Tissue Repair

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current tissue engineering scaffolds face challenges in achieving specific and stable bioactive coatings that effectively interact with endothelial cells and progenitor cells for improved vascularization and angiogenesis, due to the lack of specificity and stability of existing biomolecules, leading to non-specific cell binding and detrimental body responses.

Innovation Solution

Development of scaffolds with a polymer and a cyclic peptide ligand covalently immobilized on the surface, specifically designed to increase attachment of endothelial cells and progenitor cells, using a compound of Formula I that includes D-amino acids and a linker, enhancing endothelialization and vascularization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing biomolecules are used to coat synthetic scaffolds, then cell attachment is improved, but specificity to endothelial cells is lost and non-specific binding to other cell types occurs

Engineering Contradiction:

Improvecell attachment stabilityVSAvoidnon-specific cell binding

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing a peptide ligand with specific local sequence features (RGD motif combined with additional amino acids) that confer selective binding properties. The ligand's specific amino acid composition and structure create localized interaction sites that preferentially bind to integrins on endothelial cells while avoiding non-specific binding to other cell types.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by modifying the peptide sequence parameters (amino acid composition, length, and structure) to optimize binding specificity. The cyclic structure and specific amino acid substitutions change the physical-chemical parameters of the ligand, enabling selective interaction with endothelial cell integrins while maintaining stable attachment.

Inventive Principle:

Principle #35Parameter changes

2Shape

If synthetic materials are designed to mimic ECM physical structure, then structural support is provided, but bioactive motifs are lacking

Engineering Contradiction:

ImproveECM physical structureVSAvoidlack of bioactive function

Core Design Contradiction:

ShapeVSObject-generated harmful factors

Solution Approach 1:

The patent merges the physical structure-mimicking capability of synthetic materials with the bioactive functionality of natural ECM peptides. The synthetic scaffold provides the structural framework while the covalently attached peptide ligand provides the bioactive motifs, combining both functions into a single integrated system.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a composite material system consisting of synthetic polymer scaffold combined with bioactive peptide ligands. This composite approach allows the synthetic component to provide structural integrity while the peptide component provides biological activity, achieving both structure and function.

Inventive Principle:

Principle #40Composite materials

3Reliability

If biomolecules are used to improve endothelialization, then vascularization is enhanced, but structural stability and translational application are compromised

Engineering Contradiction:

Improvevascularization functionVSAvoidbiomolecule structure stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by covalently immobilizing the peptide ligand on the scaffold surface before cell seeding and implantation. This pre-attachment ensures the bioactive molecules are stably positioned to guide endothelial cell attachment and vascularization from the outset, maintaining structural integrity throughout the vascularization process.

Inventive Principle:

Principle #10Preliminary 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 peptide ligand scaffold significantly improves the attachment and specificity of endothelial cells and progenitor cells, promoting vascularization and reducing non-specific binding to other cell types, thereby enhancing the biological functions and regenerative potential of engineered tissues.

Implementation Method 1

a polymer and a cyclic peptide ligand covalently immobilized on the surface

Methodology Applied

Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

the peptide ligand increases the attachment of endothelial cells and/or progenitor cells to the scaffold

Methodology Applied

Scientific EffectCell adhesion: Adhesive

Data Source

PatentUS20220313867A1Engineered scaffolds for vascularized tissue repair

Publication Date: 2022.10.06 RGT UNIV OF CALIFORNIA

AI summary

The present invention provides scaffolds that include a polymer and a cyclic peptide ligand. The peptide ligand increases the attachment of endothelial cells and/or progenitor cells to the scaffold. The present invention also provides engineered tissues that include the provided scaffolds. The present invention also provides coatings that include a coating polymer and a cyclic peptide ligand. The present invention also provides methods of improving endothelialization and vascularization of endothelial cells and/or progenitor cells for tissue regeneration in a subject and of repairing bone defects in a subject, by implanting a provided scaffold.