Lyosecretome-Loaded 3D Bio-Printed Bone Scaffold

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Solution Overview

Problem

Current bone tissue engineering methods using three-dimensional scaffolds loaded with stem cells face challenges such as rejection reactions, tumor induction, infection transmission, complex production processes, and difficulties in achieving controlled release of active substances, particularly in scaffolds with complex geometries and high porosity.

Innovation Solution

A scaffold loaded with lyosecretome, specifically mesenchymal stem cell secretome in lyophilized form, is developed using 3D bio-printing techniques, allowing for controlled release of proteins and lipids through the use of alginate and fibroin hydrogels, which enhances osteoinductive capacity and avoids the limitations of stem cell use, enabling rapid or slow bone regeneration based on clinical needs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cells are used to load scaffolds for bone regeneration, then tissue regeneration capability is improved, but rejection reactions, tumor induction, and infection transmission risks increase

Engineering Contradiction:
Improvetissue regeneration capabilityVSAvoidrejection reactions, tumor induction, infection transmission
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates the beneficial secretome from stem cells, separating the regenerative factors (proteins, lipids, growth factors) from the harmful aspects of whole stem cell transplantation. This extraction allows the scaffold to deliver regenerative signals without introducing living cells that could cause rejection, tumors, or infections.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The secretome acts as an intermediary substance that mediates the regenerative effect without requiring direct stem cell implantation. The scaffold loaded with secretome delivers the biological signals needed for bone regeneration while avoiding the direct contact and immune response issues associated with whole stem cell transplantation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If scaffolds with complex geometries and high porosity are used to improve bone regeneration, then tissue integration is enhanced, but controlled release of active substances becomes difficult

Engineering Contradiction:
Improvetissue integrationVSAvoidcontrolled release of active substances
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by differentiating the scaffold structure into regions with different properties: the outer framework maintains complex geometry and high porosity for tissue integration, while specific zones contain hydrogel matrices with controlled porosity and composition tailored for controlled release of specific secretome components. This allows simultaneous optimization of both tissue integration and controlled release.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The scaffold employs composite materials combining the structural support material (e.g., PCL, PLA) with hydrogel matrices (alginate, fibroin) that have different degradation and release profiles. This composite structure enables the scaffold to simultaneously provide mechanical support with complex geometry for tissue integration and controlled release pathways for active substances.

Inventive Principle:
Principle #40Composite materials

3Ease of manufacture

If conventional manufacturing techniques are used to produce scaffolds, then production simplicity is maintained, but controlled porosity and specific shape properties are limited

Engineering Contradiction:
Improveproduction simplicityVSAvoidcontrolled porosity and specific shape
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent utilizes parameter changes in the 3D bio-printing process to achieve controlled porosity and specific shapes. By adjusting printing parameters (layer thickness, infill density, extrusion rate, temperature) and material parameters (viscosity, composition), the scaffold can be manufactured with precise geometric control and tailored porosity distributions while maintaining the capability to produce complex patient-specific geometries.

Inventive Principle:
Principle #35Parameter changes

4Productivity

If rapid bone regeneration is needed, then treatment time is reduced, but control over release kinetics becomes more challenging

Engineering Contradiction:
Improvebone regeneration speedVSAvoidcontrol over release kinetics
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent implements dynamic control of release kinetics through the use of hydrogel matrices with tunable degradation rates and compositions. The scaffold can be designed to release secretome components at different rates over time, allowing optimization of bone regeneration speed while maintaining control over the release profile through material selection and structural design.

Inventive Principle:
Principle #15Dynamics

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 scaffold achieves improved bone regeneration with controlled release of active substances, overcoming previous limitations in tissue engineering by ensuring structural stability and efficient delivery of bioactive materials, promoting optimal integration and regeneration without the need for immunosuppressive therapies or surgical reintervention.

Implementation Method 1

controlled release of proteins and lipids through the use of alginate and fibroin hydrogels

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

alginate and fibroin hydrogels, which enhances osteoinductive capacity

Methodology Applied
Scientific EffectHydrogel degradation: Decomposition (biological)

Implementation Method 3

A scaffold loaded with lyosecretome, specifically mesenchymal stem cell secretome in lyophilized form, is developed using 3D bio-printing techniques

Methodology Applied
Scientific Effect3D bio-printing: 3D Printing

Implementation Method 4

mesenchymal stem cell secretome in lyophilized form

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Implementation Method 5

controlled release of proteins and lipids

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentUS20240148936A1Scaffold for tissue regeneration, particularly for bone regeneration, and manufacturing method thereof
Publication Date: 2024.05.09 PHARMAEXCEED SRL
  • US20240148936A1 patent drawing
  • US20240148936A1 patent drawing
  • US20240148936A1 patent drawing

AI summary

A scaffold for tissue regeneration, particularly for bone regeneration, comprises a three-dimensional supporting structure made of a biocompatible and biodegradable material; the supporting structure is functionalized with secretome, in particular mesenchymal stem cell secretome, preferably in lyophilized form (lyosecretome).