Injectable Cryogel Scaffolds for Minimally Invasive Tissue Regeneration

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Solution Overview

Problem

Current surgical implantation of three-dimensional scaffolds is invasive and causes trauma, including pain, bleeding, and bruising, due to the need for incisions and anesthesia.

Innovation Solution

Development of an injectable device comprising a cryogel composition with open interconnected macropores, characterized by shape memory and comprising crosslinked gelatin or alginate polymers, allowing for minimally invasive delivery through a needle, which can be loaded with cells and therapeutics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If surgical implantation of three-dimensional scaffolds is performed, then structural support for tissue regeneration is achieved, but patient trauma including pain, bleeding, and bruising occurs

Engineering Contradiction:
Improvestructural supportVSAvoidpatient trauma
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The scaffold material undergoes a phase transition from solid to gel state, allowing it to be injected through a needle and then revert to its solid structural form at the target site. This parameter change enables minimally invasive delivery while maintaining structural support functionality.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The cryogel scaffold utilizes phase transition properties to change from a solid macroscopic structure to an injectable gel state, then back to solid form after implantation. This phase transition mechanism resolves the contradiction between structural integrity and minimally invasive delivery.

Inventive Principle:
Principle #36Phase transitions

2Object-affected harmful factors

If large macroscopic scaffolds are delivered through minimally invasive means, then patient trauma is reduced, but maintaining structural integrity during injection becomes difficult

Engineering Contradiction:
Improvepatient traumaVSAvoidstructural integrity
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The scaffold's physical state is changed from solid to gel during injection, allowing deformation without structural damage. After injection, the parameter reverts to solid state, restoring full structural integrity. This parameter transformation enables both minimally invasive delivery and structural stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The scaffold exhibits dynamic properties, being deformable during injection but stable after implantation. This dynamic behavior allows the scaffold to adapt to different mechanical requirements during delivery and functional phases.

Inventive Principle:
Principle #15Dynamics

3Strength

If preformed macroscopic scaffolds are used, then structural support is optimized, but invasive surgical implantation is required

Engineering Contradiction:
Improvestructural supportVSAvoidimplantation procedure
Core Design Contradiction:
StrengthVSEase of operation

Solution Approach 1:

The scaffold utilizes phase transition between solid and gel states to enable injection through a needle. The preformed macroscopic structure provides optimized structural support, while the phase transition to gel state enables minimally invasive injection, eliminating the need for open surgical implantation.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The scaffold is delivered using hydraulic injection through a syringe and needle system. This allows the preformed scaffold to be pushed through a small gauge needle in a minimally invasive manner, improving ease of operation while maintaining structural integrity.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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

Enables the delivery of cells and therapeutics with high precision to target sites with reduced invasiveness, maintaining structural integrity and promoting tissue regeneration while minimizing trauma and side effects.

Implementation Method 1

when an appropriate shear stress is applied, the deformable hydrogel is dramatically and reversibly compressed (up to 90% of its volume) resulting in injectable macroporous preformed scaffolds

Methodology Applied
Scientific EffectShear stress-induced reversible compression: Viscoelasticity

Implementation Method 2

wherein said cryogel composition comprises a crosslinked gelatin polymer or a crosslinked alginate polymer

Methodology Applied
Scientific EffectCrosslinking: Chemical Bonding

Implementation Method 3

Hydrogels are highly absorbent (they can contain over 99% water) natural or synthetic polymers that possess a degree of flexibility very similar to natural tissue, due to their significant water content

Methodology Applied
Scientific EffectHydrophilicity: Hydrophile

Implementation Method 4

wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle

Methodology Applied
Scientific EffectShape memory: Shape Memory Polymer

Data Source

PatentEP3417876B1Injectable preformed macroscopic 3-dimensional scaffolds for minimally invasive administration
Publication Date: 2021.03.31 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • EP3417876B1 patent drawingFigure 1
  • EP3417876B1 patent drawingFigure 2
  • EP3417876B1 patent drawingFigure 3A~3E

AI summary

The present application discloses an injectable device comprising a cell-adhesive cryogel composition comprising open interconnected macropores, wherein said cryogel composition comprises at least 75% pores, wherein said cryogel composition is characterized byshape memory following deformation by compression through a needle, wherein said cryogel composition comprises a crosslinked gelatin polymer or a crosslinked alginate polymer, and wherein said cryogel composition comprises a cancer antigen.