Decellularized Matrix Microspheres for Osteochondral Regeneration

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Solution Overview

Problem

Current treatments for large osteochondral injuries, particularly those exceeding 2.5 cm2 in pediatric and adolescent patients, lack effective methods for restoring functional cartilage and maintaining a stable bone-peri-articular cartilage interface that can withstand joint forces, with existing tissue-engineered approaches falling short in promoting long-term cartilage regeneration.

Innovation Solution

Development of thermally stable matrix microspheres containing decellularized donor tissue, encapsulated in polymeric materials, which are integrated into 3D printed filaments to enhance cell migration, proliferation, and chondrogenesis, providing a sustained release of growth factors and proteoglycans to promote cartilage regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatment methods (micro-fracture, ACI, OAT) are used for large osteochondral injuries, then some quality of life improvement is achieved, but functional cartilage regeneration akin to native tissue cannot be accomplished and the bone-peri-articular cartilage interface remains unstable

Engineering Contradiction:
Improvecartilage regeneration qualityVSAvoidtreatment effectiveness for large injuries
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention segments the treatment approach by using decellularized cartilage matrix as a scaffold framework, which is then populated with patient's own stem cells. This segmentation allows the complex task of cartilage regeneration to be divided into manageable components: providing structural support through the decellularized matrix and facilitating cell differentiation and tissue formation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The decellularized cartilage matrix acts as an intermediary between the patient's stem cells and the damaged cartilage site. It provides a bioactive environment that guides cell behavior, promotes chondrogenesis, and establishes a stable interface between bone and cartilage, overcoming the limitations of direct cell implantation methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Strength

If traditional tissue-engineered approaches are used, then some cartilage repair is achieved, but a stable bone-peri-articular cartilage interface that can withstand joint forces cannot be maintained long-term

Engineering Contradiction:
Improveinterface stabilityVSAvoidlong-term cartilage maintenance
Core Design Contradiction:
StrengthVSDuration of action of stationary object

Solution Approach 1:

The invention creates a composite structure by combining decellularized cartilage matrix with viable stem cells and growth factors. This composite approach integrates the structural integrity of the decellularized framework with the regenerative capacity of living cells, producing tissue that maintains both strength and long-term functionality.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention changes the biochemical and structural parameters of the repair tissue by using decellularized matrix that retains native cartilage architecture and bioactivity. This approach creates an environment that promotes hyaline cartilage formation rather than fibrocartilage, improving both mechanical properties and long-term durability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If microspheres containing decellularized donor tissue are incorporated into polymeric filaments, then cell migration and chondrogenesis are enhanced, but the complexity of the fabrication process increases

Engineering Contradiction:
Improvechondrogenesis promotionVSAvoidmicrosphere integration process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The decellularized cartilage matrix is processed and encapsulated into microspheres before being integrated into the polymeric filament structure. This preliminary preparation ensures that the bioactive components are properly positioned and protected, facilitating their function during the tissue regeneration process while streamlining the overall fabrication workflow.

Inventive Principle:
Principle #10Preliminary 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

The approach supports the viability and chondrogenic differentiation of human mesenchymal stem cells, offering a promising solution for large osteochondral injuries by creating a biomimetic scaffold that mimics native cartilage, potentially improving treatment outcomes for patients with significant cartilage defects.

Implementation Method 1

encapsulated in polymeric materials, which are integrated into 3D printed filaments to enhance cell migration, proliferation, and chondrogenesis, providing a sustained release of growth factors and proteoglycans

Methodology Applied
Scientific EffectSustained release: Diffusion

Data Source

PatentUS20240075183A1Microspheres Containing Decellularized Donor Tissue and Their Use in Fabricating Polymeric Structures
Publication Date: 2024.03.07 CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
  • US20240075183A1 patent drawing
  • US20240075183A1 patent drawing
  • US20240075183A1 patent drawing

AI summary

Decellularized matrix microspheres comprising a polymeric material and a donor tissue are provided. Also disclosed are structures containing a plurality of decellularized matrix microspheres incorporating a first polymer and a donor tissue; and a second polymer, wherein the decellularized matrix microspheres and the second polymer are in the form of a filament. Methods of treating a tissue injury employing the matrix microspheres and structures described as well as their methods of manufacture are also provided.