Autologous Stem Cell Conditioning for Avascular Disc Repair

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Solution Overview

Problem

Conventional stem cell therapies face challenges in repairing damaged avascular tissues, such as intervertebral discs, due to harsh environmental conditions and limited blood supply, which hinder the effectiveness of stem cell implantation and regeneration in humans compared to animal models.

Innovation Solution

The method involves procuring autologous mesenchymal stem cells from patients and conditioning them in vitro to optimize their viability in avascular environments, followed by implantation in targeted sites within the disc, often in combination with autologous platelet or platelet lysate treatments to enhance blood flow and nutrient delivery, specifically targeting the posterior disc annulus rather than the nucleus pulposus.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cells are directly implanted into the nucleus pulposus, then repair of the disc is attempted, but the harsh environmental conditions (avascular, high pressure, adverse pH) cause poor stem cell survival and limited regeneration effectiveness

Engineering Contradiction:
Improvestem cell survivalVSAvoidharsh environmental conditions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by conditioning stem cells in vitro before implantation. The cells are exposed to simulated harsh disc environment conditions (low oxygen, high pressure, adverse pH) in a controlled laboratory setting, allowing them to adapt and survive better before being implanted into the actual harsh environment of the disc.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses an intermediary approach by introducing a carrier material that facilitates stem cell delivery and protection. The carrier material serves as a mediator between the stem cells and the harsh disc environment, providing initial protection and support while the cells adapt to the new environment.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If stem cells are implanted in the nucleus pulposus, then disc repair is attempted, but the lack of blood supply limits nutrient delivery and stem cell expansion

Engineering Contradiction:
Improvestem cell expansionVSAvoidblood supply
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by pre-conditioning stem cells in vitro with simulated nutrient-limited conditions, allowing them to adapt to low nutrient environments before implantation. This preparation enables the cells to survive and expand better in the avascular disc environment without requiring immediate abundant nutrient supply.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses parameter changes by modifying the physiological parameters (oxygen levels, pH, nutrient concentration) during in vitro conditioning of stem cells. These parameter adjustments simulate the disc environment, preparing the cells to thrive under the specific parameter conditions of the avascular disc tissue.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If conventional stem cell implantation methods are used, then repair is attempted, but the mechanical stress and strain from bipedal movement prevent successful healing

Engineering Contradiction:
Improvehealing successVSAvoidmechanical stress
Core Design Contradiction:
ReliabilityVSStress or pressure

Solution Approach 1:

The patent applies preliminary action by conditioning stem cells mechanically in vitro before implantation. The cells are exposed to simulated mechanical stress and strain conditions in the laboratory, allowing them to develop mechanical resilience before facing the actual mechanical demands of disc function during bipedal movement.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies self-service by enabling the stem cells to adapt to mechanical stress through their own biological responses during in vitro conditioning. The cells undergo natural adaptation processes in response to simulated mechanical loading, developing inherent mechanical tolerance without requiring external mechanical protection devices.

Inventive Principle:
Principle #25Self-service

4Ease of manufacture

If stem cells are implanted into the nucleus pulposus, then disc repair is attempted, but the avascular nature of the disc creates a hostile environment that resists repair procedures

Engineering Contradiction:
Improverepair feasibilityVSAvoidavascular conditions
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by performing extensive in vitro conditioning of stem cells to adapt them to avascular conditions before implantation. This preliminary adaptation makes the repair procedure more feasible by ensuring the cells can survive and function in the hostile avascular environment without requiring immediate vascularization.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses parameter changes by adjusting and controlling multiple environmental parameters (oxygen tension, pH, nutrient concentration, osmolarity) during in vitro cell conditioning. These parameter modifications simulate the avascular disc environment, preparing the cells to tolerate and thrive in the otherwise hostile conditions.

Inventive Principle:
Principle #35Parameter changes

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 significantly enhances the repair and regeneration of damaged discs by improving stem cell survival and expansion within the challenging conditions of avascular zones, leading to improved clinical outcomes in humans with degenerative disc disease.

Implementation Method 1

culturing the harvested stem cells under conditions selected to enhance the cells' capacity to survive and expand within the damaged disc environment

Methodology Applied
Scientific EffectHypoxia:

Implementation Method 2

Nutrients to the disc typically arrive via small capillary beds in the subchondral bone which diffuse throughout the disc over the course of time

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS11278573B2Methods and compositions to facilitate repair of avascular tissue
Publication Date: 2022.03.22 REGENEXX LLC
  • US11278573B2 patent drawing
  • US11278573B2 patent drawing
  • US11278573B2 patent drawing

AI summary

Compositions and methods are provided for repairing damaged avascular zones, including intervertebral disc, in a patient in need thereof.