Bioreactor Load Applicator for Tissue Construct Stiffness

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Solution Overview

Problem

Current methods for forming tissue engineered constructs, particularly for cartilage repair, have been ineffective in achieving mechanical properties comparable to native cartilage, leading to inadequate stiffness and integration with surrounding tissue, due to insufficient modulus and yield strength.

Innovation Solution

A bioreactor system that applies cyclical compressive mechanical loads to tissue constructs seeded on scaffolds, where the load applicator initially contacts both the construct and a support element, allowing the support element to bear the majority of the load, thereby controlling strain and stress to stimulate matrix deposition and increase construct stiffness over time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If compressive loading is applied to stimulate matrix deposition, then tissue matrix deposition is enhanced, but the construct modulus remains significantly lower than native cartilage

Engineering Contradiction:

Improvetissue matrix depositionVSAvoidconstruct modulus

Core Design Contradiction:

Quantity of substanceVSStrength

Solution Approach 1:

The patent applies preliminary mechanical loading to cell-seeded scaffolds during the tissue formation phase to stimulate matrix deposition and cellular differentiation. By applying compressive loads early in the tissue engineering process, the construct develops better mechanical properties before implantation, addressing the contradiction between enhancing matrix deposition and achieving sufficient construct modulus.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If the construct modulus is increased to match native cartilage, then integration with surrounding tissue is improved, but the construct becomes more difficult to form and maintain during culture

Engineering Contradiction:

Improveintegration with surrounding tissueVSAvoidconstruct formation and maintenance

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs dynamic mechanical loading regimes that adapt during the culture period. The loading parameters (magnitude, frequency, duration) are adjusted over time to match the developing mechanical properties of the construct. This dynamic approach allows the construct to achieve native-like modulus while maintaining ease of culture, as the loading intensity increases progressively rather than being applied at full strength from the beginning.

Inventive Principle:

Principle #15Dynamics

3Power

If high compressive loads are applied to achieve physiological stress levels, then mechanotransductive effects are enhanced, but the scaffold and cells may be damaged

Engineering Contradiction:

Improvemechanotransductive effectVSAvoidscaffold and cell damage

Core Design Contradiction:

PowerVSObject-affected harmful factors

Solution Approach 1:

The patent applies periodic or cyclic mechanical loading to the tissue constructs during culture. By using cyclic compression rather than static high loads, the system enhances mechanotransduction while allowing recovery periods that prevent damage to the scaffold and cells. The cyclic nature of the loading (e.g., 1 Hz frequency) provides sufficient stimulus for tissue formation while avoiding the harmful effects of continuous high-stress exposure.

Inventive Principle:

Principle #19Periodic 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

This approach enables the creation of tissue engineered constructs with elastic moduli suitable for implantation, achieving stiffness comparable to native cartilage, enhancing integration and long-term repair by iteratively increasing strain and stress as the construct deposits more matrix, ultimately reaching desirable mechanical properties.

Implementation Method 1

apply a cyclical compressive mechanical load to the tissue construct, to stimulate the deposition of tissue matrix in the tissue construct

Methodology Applied

Scientific EffectMechanotransduction:

Implementation Method 2

the load applicator can at least initially contact both the tissue construct and the tissue construct support element, so that at least part of a total load generated by the load applicator is borne by the tissue construct support element

Methodology Applied

Scientific EffectElasticity: Elasticity

Data Source

PatentUS10801002B2Tissue engineered constructs

Publication Date: 2020.10.13 XIROS LTD

AI summary

A method of forming a tissue engineered construct, a bioreactor for forming a tissue engineered construct, and a tissue engineered construct itself are disclosed. The disclosed method includes seeding a scaffold with cells to form a tissue construct; locating the tissue construct in a space defined by a tissue construct support element; locating the tissue construct support element within a bioreactor; and operating a load applicator of the bioreactor to apply a cyclical compressive mechanical load to the tissue construct, to stimulate the deposition of tissue matrix in the tissue construct; in which the tissue construct, the tissue construct support element and the load applicator are arranged so that the load applicator can at least initially contact both the tissue construct and the tissue construct support element, so that at least part of a total load generated by the load applicator is borne by the tissue construct support element.