Bioreactor Cyclic Strain for Skeletal Muscle Tissue Organization

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Solution Overview

Problem

Current methods for tissue engineering of skeletal muscle in vitro face challenges in creating clinically applicable, functional muscle tissues due to the limitations of gel-based constructs being too small and fragile for surgical manipulation, lacking a bioreactor system that effectively accelerates cellular organization and tissue formation.

Innovation Solution

A method involving cyclic stretching and relaxing of precursor muscle cells on a support within a bioreactor system, combined with controlled cyclic strain using a device equipped with a motor and controller, to enhance the functionality and organization of skeletal muscle tissue, allowing for the production of contractile and structurally robust muscle constructs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gel-based constructs (collagen or fibrin) are used to engineer 3-D skeletal muscle tissue, then cellular organization and tissue formation are improved, but the constructs become too small and fragile for surgical manipulation

Engineering Contradiction:
Improvetissue formation capabilityVSAvoidstructural robustness
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent combines biodegradable scaffolds (collagen or fibrin gels) with synthetic scaffolds to create a composite structure. The biodegradable component provides cellular organization and tissue formation capability, while the synthetic component provides structural strength and size. This composite approach allows the construct to achieve both biological functionality and mechanical robustness suitable for surgical manipulation.

Inventive Principle:
Principle #40Composite materials

2Reliability

If gel-based constructs are used for muscle tissue engineering, then functional tissue development is improved, but the constructs lack sufficient size for clinical application

Engineering Contradiction:
Improvefunctional tissue developmentVSAvoidconstruct size
Core Design Contradiction:
ReliabilityVSVolume of moving object

Solution Approach 1:

By combining biodegradable scaffolds with synthetic scaffolds, the patent creates constructs that achieve both functional tissue development and clinically relevant size. The synthetic scaffold provides the necessary volume and structural framework, while the biodegradable scaffold enables functional tissue formation within that framework.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent uses modular scaffold components that can be assembled to achieve clinically relevant sizes. The synthetic and biodegradable scaffold components can be configured in different ratios and arrangements to produce constructs of appropriate volume for specific clinical applications while maintaining functional tissue development capability.

Inventive Principle:
Principle #1Segmentation

3Adaptability or versatility

If biodegradable scaffolds are used for muscle engineering, then tissue compatibility is improved, but development barriers (structural and nutritional) increase

Engineering Contradiction:
Improvetissue compatibilityVSAvoiddevelopment barrier
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent combines biodegradable scaffolds with synthetic scaffolds to create a composite structure where the synthetic component provides structural stability and nutritional support, reducing the development barriers inherent in biodegradable materials alone. The biodegradable component maintains tissue compatibility while the synthetic component compensates for structural and nutritional limitations.

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

This approach accelerates the formation of functional skeletal muscle tissue with enhanced contractile responses and structural integrity, enabling the creation of clinically relevant-sized muscle constructs suitable for surgical implantation and reconstruction.

Implementation Method 1

cyclically stretching and relaxing the support at least twice along a first axis during a first time period

Methodology Applied
Scientific EffectMechanical strain: Deformation

Implementation Method 2

cyclically stretching and relaxing the support at least twice along a first axis during a first time period

Methodology Applied
Scientific EffectMechanical force: Mechanical Force

Data Source

PatentUS9757225B2Bioreactor system and method of enhancing functionality of muscle cultured in vitro
Publication Date: 2017.09.12 WAKE FOREST UNIVERSITY HEALTH SCIENCES INC
  • US9757225B2 patent drawing
  • US9757225B2 patent drawing
  • US9757225B2 patent drawing

AI summary

A method of producing organized skeletal muscle tissue from precursor muscle cells in vitro comprises: (a) providing precursor muscle cells on a support in a tissue media; then (b) cyclically stretching and relaxing the support at least twice along a first axis during a first time period; and then (c) optionally but preferably maintaining the support in a substantially static position during a second time period; and then (d) repeating steps (b) and (c) for a number of times sufficient to enhance the functionality of the tissue formed on the support and/or produce organized skeletal muscle tissue on the solid support from the precursor muscle cells.