Layer-by-Layer Fabrication of Tissue-Engineered Vascular Grafts

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Solution Overview

Problem

Current methods for producing small diameter blood vessel grafts face challenges such as high thrombosis risk due to low blood flow velocities, limited availability of autografts, and variability in diameter and compliance, leading to intimal hyperplasia and graft failure.

Innovation Solution

A method for fabricating multilayer hollow tubes using a layer-by-layer rod dipping approach with controlled fabrication parameters, incorporating functionalized gelatin and alginate, and cell-compatible hydrogels, allowing for automated production of complex vascular structures with aligned fibers and homogenous cell distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If autografts are used for SDBV bypass surgeries, then blood compatibility is improved, but donor site comorbidity and limited availability worsen

Engineering Contradiction:

Improveblood compatibilityVSAvoidavailability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates tissue-engineered small diameter blood vessels that copy the structure and function of natural blood vessels using decellularized allograft scaffolds. The scaffolds retain the natural extracellular matrix architecture while allowing repopulation with patient-specific cells, providing blood compatibility without requiring donor site harvesting.

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent modifies the physical and chemical parameters of the graft by controlling the decellularization process to preserve critical blood-compatible components of the extracellular matrix while removing cellular material that could cause rejection. This allows the graft to maintain natural blood compatibility while eliminating availability limitations.

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If synthetic constructs are used for large diameter vessels, then ease of manufacture is improved, but physiological requirements for SDBV worsen

Engineering Contradiction:

Improveease of manufactureVSAvoidphysiological requirements

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent combines the manufacturing simplicity of synthetic materials with the physiological functionality of natural extracellular matrix. The decellularized allograft scaffolds provide a natural-like environment that supports cell growth and function while maintaining structural integrity, bridging the gap between synthetic ease of manufacture and natural physiological requirements.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent segments the vessel wall into distinct layers (tunica intima, media, and externa) that can be independently engineered and assembled. This allows each layer to be optimized for its specific physiological function while maintaining overall vessel performance, enabling customization for different vessel sizes and locations.

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If manual fabrication methods are used for tissue engineered SDBV, then customization is improved, but scalability and reproducibility worsen

Engineering Contradiction:

ImprovecustomizationVSAvoidscalability

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent replaces manual mechanical fabrication with automated bioreactor systems that can consistently produce grafts with controlled parameters. These systems automate cell seeding, scaffold processing, and graft assembly, enabling scalable production while maintaining customization through programmable control of fabrication parameters.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent establishes standardized parameter ranges for scaffold fabrication, cell seeding density, and processing conditions that ensure reproducible results across multiple production batches. By defining optimal parameter windows rather than fixed values, the system maintains flexibility for customization while ensuring scalability and reproducibility.

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

This method enables the creation of scalable, reproducible, and biologically compatible vascular grafts with improved mechanical strength and reduced thrombogenicity, capable of mimicking natural blood vessel structures for various biomedical applications.

Implementation Method 1

exposing the pre-polymerized solution attached to the rod to light, visible, UV light or infrared depending on the nature of the photo-initiator while the rod is rotating and emerging from the pre-polymerized solution to obtain a polymerized or crosslinked layer

Methodology Applied

Scientific EffectPhotopolymerization: Photopolymerisation

Data Source

PatentEP3361986B1Automated fabrication of layer-by-layer tissue engineered complex tubes

Publication Date: 2021.01.06 RIVET PTY LTD

Figure 1(a)~1
Figure 2A~2B
Figure 3a~3c

AI summary

The present invention overcomes all the above drawbacks and provides a versatile method for the fabrication of multilayer hollow tubes that uses a layer-by-layer rod dipping approach using different biomaterials. The device enables fine control over fabrication parameters, such as ascending/descending speeds, rod rotational velocity, and crosslinking or polymerization time. All these technologies allows the generation of more complex multilayer hollow tubes such as vessel-like structures, urethral grafting, prostate grafting and the like.