Hydroxypropylcellulose Scaffold with Interconnected Macropores

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Solution Overview

Problem

Existing methods for forming macroporous scaffolds often result in non-interconnected pores with limited depth distribution, requiring complex procedures and lacking the desired porosity and mechanical properties for tissue engineering applications.

Innovation Solution

A scaffold composed of hydroxypropylcellulose partially substituted with self-crosslinkable groups, such as allyl isocyanate, is formed through phase separation and γ-ray crosslinking, resulting in macropores with interconnected porosity of 50% or higher and average pore sizes greater than 50 microns, facilitating cell growth and tissue formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If conventional macroporous scaffold formation methods (salt leaching, gas foaming, emulsion freeze drying) are used, then macropores can be formed, but the pores are non-interconnected with limited depth distribution

Engineering Contradiction:
Improvepore structureVSAvoidinterconnected porosity
Core Design Contradiction:
ShapeVSReliability

Solution Approach 1:

The invention utilizes liquid-liquid phase separation to form a bicontinuous emulsion structure where polymer-rich and water-rich phases interpenetrate. By controlling the phase separation process and subsequent crosslinking, interconnected macropores are formed as the water-rich phase is removed, creating a three-dimensional network of connected pores throughout the scaffold structure.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The invention employs a composite approach by combining hydroxypropylcellulose with a crosslinking agent (glycidyl methacrylate) to form a crosslinked polymer network. This composite structure maintains mechanical integrity while allowing the formation of interconnected pores through the phase separation process, resolving the contradiction between pore connectivity and structural stability.

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If complex procedures are used to form macroporous scaffolds, then porosity can be achieved, but the manufacturing complexity increases

Engineering Contradiction:
ImproveporosityVSAvoidprocedure complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention employs self-crosslinking of hydroxypropylcellulose through reaction with glycidyl methacrylate, eliminating the need for separate crosslinking agents or complex multi-step procedures. The polymer itself provides the crosslinking functionality, simplifying the manufacturing process while maintaining high porosity through the phase separation mechanism.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention controls porosity and pore interconnectivity by adjusting parameters such as polymer concentration, crosslinking degree, and phase separation conditions. By optimizing these parameters, high interconnected porosity is achieved through a relatively simple one-step crosslinking process rather than multiple complex steps.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high porosity is achieved in macroporous scaffolds, then cell migration is facilitated, but mechanical integrity may be compromised

Engineering Contradiction:
Improveinterconnected porosityVSAvoidmechanical integrity
Core Design Contradiction:
Quantity of substanceVSStrength

Solution Approach 1:

The invention creates a composite crosslinked polymer network where hydroxypropylcellulose chains are covalently linked through glycidyl methacrylate crosslinking points. This network structure provides mechanical strength to support high interconnected porosity, as the crosslinked framework maintains structural integrity even with 50% or higher porosity.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The crosslinking is distributed throughout the polymer matrix, creating localized crosslinking points that reinforce the structure without blocking the macropores. This local reinforcement strategy maintains mechanical integrity while preserving the interconnected pore network necessary for cell migration and nutrient transport.

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

The scaffold provides a 3D structure with high interconnected porosity, mechanical integrity, and hydrophilicity, suitable for soft tissue engineering, allowing for cell migration, tissue formation, and sustained bioactive molecule release, while being biocompatible and easily fabricated.

Implementation Method 1

inducing phase separation in a solution comprising a polymer precursor and water, to form a bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase

Methodology Applied
Scientific EffectPhase separation: Phase Change

Implementation Method 2

crosslinking the partially substituted hydroxypropylcellulose through the self-crosslinkable group to form a polymer defining at least partially interconnected macropores. The crosslinking may comprise irradiating the emulsion with γ-ray

Methodology Applied
Scientific Effectγ-ray crosslinking: Radiation

Implementation Method 3

Water may be removed from the pores by freeze-drying the polymer

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Data Source

PatentEP2234655B1Forming porous scaffold from cellulose derivatives
Publication Date: 2018.12.12 AGENCY FOR SCI TECH & RES
  • EP2234655B1 patent drawingFigure 1
  • EP2234655B1 patent drawingFigure 2~4
  • EP2234655B1 patent drawingFigure 5

AI summary

Scaffold comprises a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, which is crosslinked through the self-crosslinkable group. The macropores have an average pore size larger than 50 microns and are at least partially interconnected. In one method, bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase is formed. The polymer phase comprises hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, and is crosslinked through the self-crosslinkable group to form a polymer defining at least partially interconnected pores. In another method, phase separation is induced in a solution comprising a polymer precursor and water to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase. The polymer precursor comprises a self-crosslinkable group and is crosslinked through the self-crosslinkable group in the emulsion to form a polymer defining at least partially interconnected macropores.