Biomatrix Layer Mimics Extracellular Matrix via Phase Separation

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Solution Overview

Problem

Conventional heparin-containing hydrogels are bulky, expensive to produce, and difficult to incorporate bio-functional peptides, limiting their ability to properly mimic the extracellular matrix and thus their biomedical applications.

Innovation Solution

A biomatrix layer based on liquid-liquid phase separation and glycosaminoglycan-peptide interaction, allowing for the creation of a combinatorial library of biomatrix films with adjustable biochemical composition, mechanical properties, and morphology, enabling selective cell culture and device coating.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional heparin-containing hydrogels are used to mimic extracellular matrix, then ECM-mimicking capability is achieved, but the hydrogels become bulky and expensive to produce

Engineering Contradiction:
ImproveECM-mimicking capabilityVSAvoidhydrogel volume
Core Design Contradiction:
ReliabilityVSVolume of stationary object

Solution Approach 1:

The patent applies this principle by developing thin film hydrogels instead of bulky bulk hydrogels. The hydrogel is formed as a thin coating on solid supports, dramatically reducing volume while maintaining ECM-mimicking functionality. This allows the hydrogel to provide cell interaction surfaces without the excessive material consumption and cost associated with bulk hydrogels.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The patent changes the physical parameters of the hydrogel system by controlling film thickness, porosity, and crosslinking density. By adjusting these parameters during fabrication, the hydrogel achieves optimal ECM-mimicking properties in a thin film format, resolving the contradiction between functionality and volume.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional heparin-containing hydrogels are used, then ECM-mimicking capability is achieved, but production cost increases

Engineering Contradiction:
ImproveECM-mimicking capabilityVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

By forming hydrogels as thin films on solid supports, the patent dramatically reduces the quantity of expensive heparin and other biomaterials required. This thin film approach maintains all necessary ECM-mimicking functions while reducing material costs and simplifying manufacturing processes.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The patent uses solid supports as templates or copies upon which the hydrogel is formed. This allows the ECM-mimicking functionality to be provided by a thin coating rather than requiring large volumes of expensive hydrogel material, thereby reducing production costs while maintaining reliability.

Inventive Principle:
Principle #26Copying

3Reliability

If conventional heparin-containing hydrogels are used, then ECM-mimicking capability is achieved, but incorporation of bio-functional peptides becomes difficult

Engineering Contradiction:
ImproveECM-mimicking capabilityVSAvoidpeptide incorporation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent incorporates bio-functional peptides into the hydrogel network during the fabrication process itself, before the hydrogel is applied. This preliminary incorporation simplifies the overall process by avoiding subsequent complex modification steps, while ensuring uniform distribution of peptides throughout the thin film structure.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent creates a composite material system combining heparin, bio-functional peptides, and crosslinking agents in a unified hydrogel formulation. This composite approach allows all components to be integrated simultaneously during fabrication, simplifying the process compared to sequential addition and improving the overall ECM-mimicking capability through synergistic interactions.

Inventive Principle:
Principle #40Composite materials

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 biomatrix layer effectively mimics the extracellular matrix, supporting cell proliferation and differentiation, and is stable, easy, and cost-effective to produce, making it suitable for various biomedical applications.

Implementation Method 1

a biomatrix layer with a thickness in the range from 3 nm to 40 μm, comprising, consisting essentially of or consisting of a negatively charged polymer (NCP) and a peptide-polyethylene glycol-conjugate

Methodology Applied
Scientific EffectNon-covalent interaction: Van der Waals Force

Implementation Method 2

a negatively charged polymer (NCP) at a concentration in the range of 0.1 μM to 1,000 μM and a peptide-polyethylene glycol-conjugate

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS11648320B2Non-covalently assembled biomatrix layer
Publication Date: 2023.05.16 SAINT GOBAIN PERFORMANCE PLASTICS CORP
  • US11648320B2 patent drawing
  • US11648320B2 patent drawing
  • US11648320B2 patent drawing

AI summary

The present invention provides a biomatrix layer comprising, consisting essentially of or consisting of a sulfated oligosaccharide at a concentration in the range of 0.1 μM to 1,000 μM and a peptide-polyethylene glycol-conjugate according to formula (I): PEG-R1-(BX)n (I) wherein B is lysine or arginine, X is selected from alanine, glycine, serine, threonine, tyrosine, glutamic acid or aspartic acid and n is an integer selected from 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20; R1 may be absent or is a peptide comprising 5 to 30 amino acids; PEG is comprised at a concentration in the range of 0.1 μM to 1,000 μM; R1, if present, is comprised at a concentration in the range of 0.1 μM to 4,000 μM; (BX)n is comprised at a concentration in the range of 0.25 μM to 1,000 μM. The invention further relates to processes for assembling the biomatrix layer. The biomatrix layer can be used in various biomedical applications, such as neuroprostheses, biosensors, nerve grafts, cell culture and encapsulation of cells and microorganisms as well as for drug delivery.