Poloxamer P188 Stabilizes Adipocyte Membranes

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Solution Overview

Problem

Current methods for soft tissue reconstruction using autologous fat transplantation face challenges with unpredictable high levels of reabsorption and irregularities due to mechanical stresses, ischemic changes, and insufficient vascular supply, leading to apoptosis and graft failure.

Innovation Solution

A composition comprising adipocytes and a triblock copolymer, specifically poloxamer P188, is used to stabilize cell membranes, preventing damage during procurement, handling, and transplantation, thereby increasing adipocyte viability and reducing apoptosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If free fat grafts are used for soft tissue reconstruction, then minimal donor site morbidity and ease of procedure are achieved, but unpredictable high levels of reabsorption and graft failure occur

Engineering Contradiction:
Improveease of procedureVSAvoidpredictability of graft survival
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-treating adipocytes with a membrane stabilization agent (such as hydroxyethyl starch or other polymers) before transplantation. This pre-treatment stabilizes cell membranes in advance, protecting them from mechanical stress and ischemic injury during the transplantation process, thereby reducing apoptosis and improving graft survival predictability while maintaining procedural simplicity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces an intermediary substance (membrane stabilization agent) that mediates between the adipocytes and the harsh transplantation environment. This agent acts as a protective intermediary, shielding cells from mechanical stress, shear forces, and ischemic damage during harvesting, handling, and implantation, thereby improving graft reliability without complicating the surgical procedure

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If mechanical stress and handling are applied during fat graft procurement and transplantation, then the graft can be harvested and implanted, but cell membrane damage and apoptosis increase

Engineering Contradiction:
Improvegraft harvesting and implantationVSAvoidcell membrane damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies beforehand cushioning by incorporating membrane stabilization agents into the adipocyte suspension before transplantation. These agents (such as hydroxyethyl starch, dextran, or other polymers) form a protective cushion around cell membranes, absorbing mechanical stress and shear forces during harvesting and handling, thereby preventing membrane damage and apoptosis while enabling efficient graft procurement and implantation

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The patent applies parameter changes by modifying the physical-chemical properties of the adipocyte suspension through addition of membrane stabilization agents. These agents alter the viscosity, osmotic pressure, and mechanical resilience of the cell suspension, creating a more protective environment that reduces membrane damage during handling while maintaining harvestability and implantability

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If insufficient vascular supply is present in the graft, then the procedure remains simple, but nutrient deprivation and cell death occur

Engineering Contradiction:
Improveprocedure simplicityVSAvoidnutrient deprivation
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-stabilizing cell membranes with membrane stabilization agents before transplantation. This pre-stabilization protects cells from ischemic injury and nutrient deprivation during the critical period before revascularization occurs, allowing simple surgical procedures to achieve better cell survival without requiring complex vascular anastomosis

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 use of poloxamer P188 significantly reduces fat graft reabsorption and improves cell survival, resulting in more predictable and permanent fat transplantation outcomes with enhanced adipocyte viability and tissue restoration.

Implementation Method 1

the cell membrane is protected from damage during procurement of the graft, handling of the graft (e.g., washing, storage), and/or finally the transplantation procedure

Methodology Applied
Scientific EffectMembrane stabilization:

Data Source

PatentEP2350274B1Cell transplantation
Publication Date: 2019.01.23 THE GENERAL HOSPITAL CORP
  • EP2350274B1 patent drawingFigure 1A~1B
  • EP2350274B1 patent drawingFigure 2
  • EP2350274B1 patent drawingFigure 3A~3B

AI summary

The present invention provides polymers for use in preventing damage to the membranes of cells in fat grafts. Mixing of a triblock copolymer such as poloxymer P 188 with adipocytes or adipose tissue to be transplanted into a subject is thought to stabilize the membranes of the cells leading to more successful fat transplantation in soft tissue reconstruction or augmentation. Such methods may also be used in the transplantation of adult stem cells or other cells derived from fat tissue. Other agents such as lipoic acid may also be added to the polymer/cell compositions for cell transplantation.