Silk Protein Scaffold for Cell Integration

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Solution Overview

Problem

Current tissue engineering methods face challenges in creating mechanically robust, three-dimensional scaffolds for eukaryotic cell cultivation that mimic tissue-like spreading and maintain cell viability and mechanical strength suitable for mammalian tissue engineering, while also allowing for co-cultures of multiple cell types.

Innovation Solution

A method involving the use of a silk protein, such as spider silk or silkworm fibroin, which forms a water-insoluble macrostructure when assembled in the presence of eukaryotic cells, providing a scaffold with integrated cells and allowing for the formation of various formats like fibers, foams, and films, enhancing cell compatibility and mechanical strength.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a polymeric scaffold with large pores and high interconnectivity is used to allow cell infiltration, then cell accessibility is improved, but mechanical strength and structural stability deteriorate

Engineering Contradiction:
Improvecell infiltrationVSAvoidmechanical strength
Core Design Contradiction:
Ease of operationVSStrength

Solution Approach 1:

The patent combines silk protein (natural polymer) with synthetic polymers or crosslinking agents to create composite scaffold materials that achieve both high porosity and mechanical strength. The composite structure allows large interconnected pores for cell infiltration while the combined material properties provide the necessary structural stability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The scaffold is designed with spatially varying properties: regions with large interconnected pores for cell infiltration and migration, and regions with denser structure for mechanical support. This local differentiation allows simultaneous optimization of cell accessibility and structural integrity in different parts of the scaffold.

Inventive Principle:
Principle #3Local quality

2Stability of the object's composition

If thick and stiff walls are used to maintain high porosity without collapse, then structural stability is improved, but cell compatibility and flexibility deteriorate

Engineering Contradiction:
Improvestructural stabilityVSAvoidcell compatibility
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent utilizes the unique property of silk protein to undergo conformational changes from random coil/α-helical to β-sheet structure upon assembly. This parameter change allows the material to transition from a flexible soluble state (good for cell compatibility) to a stable assembled state (good for structural integrity), resolving the contradiction between flexibility and stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The scaffold material is designed to be dynamic rather than static: silk protein chains can reorganize and adapt their conformation in response to cellular activities and mechanical loads, allowing the scaffold to maintain structural stability while remaining compatible with cell growth and tissue formation.

Inventive Principle:
Principle #15Dynamics

3Strength

If synthetic matrices with enhanced mechanical strength are used, then mechanical strength is improved, but cell viability and tissue-like properties deteriorate due to harsh formulation conditions

Engineering Contradiction:
Improvemechanical strengthVSAvoidcell viability
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent converts the typically harmful effect of silk protein aggregation into a beneficial self-assembly process. The protein naturally aggregates and forms structured fibers under mild physiological conditions, eliminating the need for harsh chemicals or high-energy processing that would harm cells, while still achieving the desired mechanical strength.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The silk protein performs self-assembly into mechanically strong structures without external intervention or harsh conditions. The protein molecules spontaneously organize into β-sheet-rich fibrous structures that provide mechanical strength, eliminating the need for toxic crosslinking agents or high-temperature processing that would compromise cell viability.

Inventive Principle:
Principle #25Self-service

4Adaptability or versatility

If natural extracellular matrix proteins are used to mimic tissue mechanical properties, then cell compatibility is improved, but manufacturing complexity and cost deteriorate

Engineering Contradiction:
Improvetissue mimicryVSAvoidmanufacturing complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent achieves tissue-like mechanical properties by controlling the conformational parameters of silk protein (inducing β-sheet formation) rather than using complex natural ECM proteins. This parameter-based approach simplifies manufacturing while achieving similar functional outcomes to natural ECM.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Instead of directly using complex natural ECM proteins that are difficult to produce synthetically, the patent creates a simplified copy or mimicry of ECM functionality using silk protein. The silk scaffold replicates the essential mechanical and biological properties of natural ECM without requiring the complex protein structures found in native extracellular matrix.

Inventive Principle:
Principle #26Copying

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

This approach results in high seeding efficiency, tissue-like cell spreading, and maintained cell viability, with cells remaining viable and proliferative within the scaffold for extended periods, and enables the creation of complex co-cultures, addressing the limitations of traditional scaffolds in mechanical strength and cell compatibility.

Implementation Method 1

a silk protein capable of assembling into a water-insoluble macrostructure

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS20190144819A1Integrated cells
Publication Date: 2019.05.16 SPIBER TECHNOLOGIES AB
  • US20190144819A1 patent drawing
  • US20190144819A1 patent drawing
  • US20190144819A1 patent drawing

AI summary

A cell scaffold material is manufactured by providing an aqueous solution of a silk protein capable of assembling into a water-insoluble macrostructure. The silk protein is mixed with eukaryotic cells, and the silk protein is assembled into a water-insoluble macrostructure in the presence of the cells, thereby forming a scaffold material for cultivating the cells. The cells can be grown integrated with the scaffold material under conditions suitable for cell culture.