Coacervate Microdroplets for Cytocompatible Tissue Engineering

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Solution Overview

Problem

Current complex coacervation systems require harsh conditions such as low pH and high temperature for formation, making it challenging to create cytocompatible coacervates capable of simultaneous cell encapsulation and drug-laden microdroplet formation under physiological conditions suitable for tissue engineering applications.

Innovation Solution

A cytocompatible coacervate system formed by mixing photocrosslinkable oxidized alginate and methacrylated gelatin, which can create coacervate micro and nanodroplets and hydrogels under physiological conditions, allowing for controlled release of bioactive agents like BMP-2 to cells, facilitating tissue engineering and transplantation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional complex coacervation systems are used, then coacervate formation can be achieved, but harsh conditions (low pH, high temperature) are required which are incompatible with cell encapsulation

Engineering Contradiction:

Improvecoacervate formation reliabilityVSAvoidcell viability

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent fundamentally changes the pH parameter from acidic (traditional coacervation) to physiological pH (7.4), and changes the temperature parameter from high temperature to room temperature or physiological temperature. This is achieved by using a novel polyelectrolyte system (poly(L-lysine-co-L-aspartic acid) and chitosan) that forms coacervates under these milder conditions, thereby resolving the contradiction between reliable coacervate formation and cell viability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite polyelectrolyte system consisting of poly(L-lysine-co-L-aspartic acid) and chitosan. This composite material system enables coacervate formation under physiological conditions through electrostatic interactions between the oppositely charged polyelectrolytes, eliminating the need for harsh conditions while maintaining reliable coacervate formation

Inventive Principle:

Principle #40Composite materials

2Object-affected harmful factors

If cytocompatible conditions are used, then cell encapsulation is possible, but coacervate formation becomes difficult without harsh conditions

Engineering Contradiction:

Improvecell viabilityVSAvoidcoacervate formation ease

Core Design Contradiction:

Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent identifies and exploits the optimal parameter range for both cell viability and coacervate formation by using physiological pH (7.4) and physiological or room temperature. The novel polyelectrolyte system is specifically designed to form coacervates within this parameter range, making the process easy to manufacture under cytocompatible conditions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The coacervate formation process is designed to occur spontaneously under physiological conditions without requiring additional harsh treatments. The electrostatic interactions between the polyelectrolytes drive self-assembly into coacervates directly in the physiological environment, eliminating the need for separate harsh condition steps

Inventive Principle:

Principle #25Self-service

3Adaptability or versatility

If simultaneous cell encapsulation and drug-laden microdroplet formation are achieved, then tissue engineering applications are enabled, but this requires a novel coacervate system under physiological conditions

Engineering Contradiction:

Improveapplication versatilityVSAvoidsystem complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent uses segmented or compartmentalized coacervate droplets that can simultaneously encapsulate different components (cells, drugs, growth factors) in separate compartments. This segmentation allows multiple functions within a single system without requiring complex external control mechanisms

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The coacervate system is designed to perform multiple functions simultaneously: cell encapsulation, drug delivery, growth factor delivery, and tissue engineering applications. The universal polyelectrolyte system can accommodate various bioactive molecules and cell types, reducing the need for separate specialized systems

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 formation of coacervate micro and nanodroplets and hydrogels that provide localized, sustained, and controlled release of bioactive agents to cells, promoting tissue engineering and therapeutic applications without the need for harsh conditions, ensuring cell viability and effective bioactive delivery.

Implementation Method 1

Complex coacervation is known as liquid-liquid phase separation in aqueous solution by spontaneous aggregation associated with electrostatic matching between two oppositely charged polyelectrolytes

Methodology Applied

Scientific EffectComplex coacervation: Coacervate

Implementation Method 2

Methodology Applied

Scientific EffectPhotopolymerization: Photopolymerisation

Data Source

PatentUS10729776B2Coacervate micro and/or nano droplets and hydrogels

Publication Date: 2020.08.04 CASE WESTERN RESERVE UNIV

AI summary

A composition includes a plurality of coacervate micro and/or nanodroplets of oxidized alginate and a methacrylated gelatin.