Decellularized Allograft Slices for Tissue Engineering

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Solution Overview

Problem

Tendon and ligament injuries pose significant challenges for functional restoration due to poor healing capabilities, particularly in ligaments which are poorly vascularized, leading to high economic burdens and the need for replacement after significant damage.

Innovation Solution

The development of composite tissue engineered tendons and ligaments using decellularized allograft slices seeded with autologous stem cells, which serve as a scaffold for regeneration, repair, or replacement, incorporating native extracellular matrix and potential reinforcement with man-made materials and growth factors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If decellularized allograft slices are used as scaffold, then cell seeding and adhesion are improved, but manufacturing complexity increases

Engineering Contradiction:
Improvecell seeding and adhesionVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The allograft tissue is divided into multiple thin slices (e.g., 10-50 micrometers thick) that can be individually processed and then stacked to form the final scaffold structure. This segmentation allows for standardized decellularization treatment of each slice while maintaining the overall tissue architecture, improving both cell seeding efficiency and manufacturing consistency.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The scaffold is constructed as a composite structure by stacking multiple decellularized tissue slices with interspersed cell-seeded layers or synthetic reinforcement materials. This composite approach combines the biological advantages of native extracellular matrix with enhanced mechanical properties and controlled cell delivery, resolving the contradiction between biological performance and manufacturing complexity.

Inventive Principle:
Principle #40Composite materials

2Strength

If multiple layers of tendon or ligament portions are stacked to form composite, then mechanical strength is improved, but device complexity increases

Engineering Contradiction:
Improvemechanical strengthVSAvoiddevice complexity
Core Design Contradiction:
StrengthVSDevice complexity

Solution Approach 1:

The final graft is segmented into multiple functional layers, each with specific mechanical properties optimized for different regions (e.g., softer inner layers, tougher outer layers). This layered segmentation allows tailoring of mechanical strength to match native tissue requirements while maintaining a relatively simple stacking and suturing fabrication process.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Multiple decellularized tissue slices are merged by stacking and suturing them together to form a unified composite structure. This merging process combines the mechanical strengths of individual slices while creating a single functional graft unit that can be implanted as one piece, balancing enhanced strength with simplified implantation procedure.

Inventive Principle:
Principle #5Merging (Combining)

3Reliability

If autologous stem cells are seeded on the composition, then tissue regeneration capability is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvetissue regeneration capabilityVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Autologous stem cells are harvested, expanded, and pre-seeded onto the decellularized tissue slices before stacking and final assembly. This preliminary cell seeding ensures optimal cell distribution and early tissue formation potential, while allowing the bulk scaffold structure to be fabricated using relatively simple stacking and suturing techniques, thus balancing regeneration capability with manufacturing simplicity.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS8894707B2Tendon or ligament tissue engineering
Publication Date: 2014.11.25 MAYO FOUNDATION FOR MEDICAL EDUCATION & RESEARCH
  • US8894707B2 patent drawing
  • US8894707B2 patent drawing
  • US8894707B2 patent drawing

AI summary

This document relates to methods and materials involved in tendon or ligament tissue engineering. For example, methods and materials for generating a composite of acellular tendon or ligament allograft slices seeded with cells and bundled into a graft for tissue repair are provided.