Growth Factor Transduced Cell-Loaded Ceramic Scaffold for Bone Regeneration

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Solution Overview

Problem

Current methods for bone regeneration, such as autologous bone grafts and precursor cells, face limitations in availability and effectiveness for critically sized bone defects, and the combination of 3D-printed calcium phosphate scaffolds with regional gene therapy is not well understood for bone repair.

Innovation Solution

A method involving 3D-printed calcium phosphate scaffolds loaded with growth factor transduced cells, specifically using a lentiviral vector system to encode bone morphogenetic protein 2, which are implanted into bone defects to stimulate bone formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If autologous bone graft is used, then bone formation effectiveness is improved, but availability and patient comfort deteriorate due to limited graft availability and harvest complications

Engineering Contradiction:
Improvebone formation effectivenessVSAvoidgraft availability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses a ceramic scaffold as an intermediary carrier to deliver growth factor-transduced cells to the bone defect site. The scaffold serves as a mediator between the gene therapy approach and bone regeneration, providing structural support while enabling controlled release of osteogenic cells and factors, thereby achieving effective bone formation without requiring autologous bone harvest

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs regional gene therapy where host cells are genetically modified to produce their own growth factors (such as BMP-2) at the implantation site. This self-service approach allows the implanted cells to autonomously produce the necessary osteogenic factors, eliminating the need for external bone graft material while achieving reliable bone regeneration

Inventive Principle:
Principle #25Self-service

2Reliability

If precursor cells are used, then bone formation potential is improved, but effectiveness deteriorates due to limited purification methods and insufficient bone formation capability

Engineering Contradiction:
Improvebone formation potentialVSAvoidbone formation effectiveness
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent fundamentally changes the functional parameters of precursor cells through genetic transduction. By introducing genes encoding osteogenic growth factors (such as BMP-2) into precursor cells, the cells are transformed from having limited bone formation capability to becoming potent osteogenic cells that actively promote bone regeneration, thereby resolving the contradiction between potential and effectiveness

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If 3D-printed calcium phosphate scaffolds are used, then custom shaping capability is improved, but understanding and optimization for regional gene therapy deteriorates due to poor comprehension of their suitability

Engineering Contradiction:
Improvecustom shaping capabilityVSAvoidsuitability for regional gene therapy
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by customizing the scaffold geometry through 3D printing to precisely match the specific bone defect morphology. The scaffold's porous structure and surface characteristics are locally optimized to enhance cell attachment, proliferation, and growth factor delivery at the implantation site, thereby ensuring reliability for regional gene therapy applications while maintaining custom shaping advantages

Inventive Principle:
Principle #3Local quality

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 achieves effective bone regeneration and healing of critically sized bone defects, as demonstrated by successful in vitro and in vivo trials, with complete healing and robust bone formation observed in rat models.

Implementation Method 1

transducing one or more cells with a growth factor essential for bone formation

Methodology Applied
Scientific EffectLentiviral transduction:

Data Source

PatentUS12133933B2Growth factor transduced cell-loaded ceramic scaffold for bone regeneration and repair
Publication Date: 2024.11.05 UNIV OF SOUTHERN CALIFORNIA
  • US12133933B2 patent drawing
  • US12133933B2 patent drawing
  • US12133933B2 patent drawing

AI summary

Disclosed herein are methods of regional gene-therapy with growth-factor transduced cells, in bone graft scenarios. In embodiments, the methods comprise use of 3D printed scaffolds.