Lyophilized CS-GAG Hydrogel Matrices for TBI Cell Delivery

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Solution Overview

Problem

Current hydrogel-based methods for in vivo stem cell delivery face challenges due to unreacted chemicals and adverse temperatures, which can negatively impact cell viability and efficacy.

Innovation Solution

The development of photopolymerized, lyophilized, bioactive chondroitin sulfate glycosaminoglycan (CS-GAG) hydrogel matrices that can be rehydrated for direct injection, providing a minimally invasive method for cellular encapsulation and enhancing cell viability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If in situ thermal or chemical crosslinking methods are used for cell encapsulation, then cell encapsulation is achieved, but cell viability and efficacy are negatively impacted due to unreacted chemicals and adverse temperatures

Engineering Contradiction:
Improvecell viabilityVSAvoidunreacted chemicals and adverse temperatures
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The hydrogel is pre-formed and sterilized before cell encapsulation, eliminating the need for in situ crosslinking. The pre-formed hydrogel matrix is then mixed with cells and administered, ensuring cells are not exposed to harmful crosslinking conditions.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

A photopolymerizable monomer mixture serves as an intermediary that enables in vivo crosslinking after cell encapsulation. The monomers are non-toxic and only polymerize when exposed to specific wavelengths of light, allowing safe cell encapsulation followed by controlled crosslinking at the implantation site.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If prefabricated hydrogels are used for cell delivery, then cell encapsulation is simplified, but the complexity of sterilization and storage increases

Engineering Contradiction:
Improvecell encapsulation processVSAvoidsterilization and storage requirements
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The hydrogel is sterilized by gamma irradiation or ethylene oxide gas sterilization, which are effective for pre-formed hydrogels. The sterilized hydrogel is then lyophilized (freeze-dried) to extend shelf life and simplify storage, converting it to a stable powder form that rehydrates before use.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Lyophilization uses phase transition (freezing followed by sublimation under vacuum) to remove water from the hydrogel, creating a stable, shelf-stable powder form that can be stored at room temperature and rehydrated before cell encapsulation and administration.

Inventive Principle:
Principle #36Phase transitions

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 method enhances cell viability and supports cell transplantation and trophic factor delivery applications, particularly in treating traumatic brain injury by providing a protective and supportive matrix for stem cells.

Implementation Method 1

purified and sterilized prefabricated photopolymerized CS-GAG hydrogels can be lyophilized

Methodology Applied
Scientific EffectPhotopolymerization: Photopolymerisation

Implementation Method 2

subsequently rehydrated with the cell suspension

Methodology Applied
Scientific EffectRehydration: Solvation

Data Source

PatentUS12090229B2Chondroitin sulfate glycosaminoglycan hydrogel matrices for the treatment of traumatic brain injury
Publication Date: 2024.09.17 UNIVERSITY OF GEORGIA RESEARCH FOUNDATION INC
  • US12090229B2 patent drawing
  • US12090229B2 patent drawing
  • US12090229B2 patent drawing

AI summary

Disclosed herein are compositions and methods for cellular reconstitution of photopolymerized, lyophilized, bioactive chondroitin sulfate glycosaminoglycan (CS-GAG)-based hydrogel matrices.