Enzymatically Cleavable Nanoparticles for Morphogen Delivery

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Solution Overview

Problem

There is a need for alternative delivery systems that can target and trigger the release of morphogens without leading to bioaccumulation, particularly in applications like tissue regeneration where existing metal and ceramic particles may accumulate in the body.

Innovation Solution

The development of hybrid multifunctional macromers that self-assemble into nanoparticles for the on-demand and targeted release of morphogens, utilizing cleavage sites responsive to enzymes secreted by mesenchymal stem cells and endothelial colony forming cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If metal and ceramic particles are used as delivery systems, then delivery functionality is achieved, but bioaccumulation risk increases

Engineering Contradiction:

Improvedelivery functionalityVSAvoidbioaccumulation risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the material parameters from inorganic (metal/ceramic) to organic biodegradable polymers, fundamentally altering the delivery system's interaction with biological systems. This parameter change enables the system to be metabolized and eliminated naturally, resolving the bioaccumulation issue while maintaining delivery functionality

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses composite material structures combining biodegradable polymer matrices with embedded morphogen cargo. This composite approach allows the system to provide both structural integrity for delivery and controlled degradability to prevent accumulation, simultaneously addressing both requirements

Inventive Principle:

Principle #40Composite materials

2Quantity of substance

If conventional delivery systems are used, then morphogen delivery is achieved, but controlled on-demand release is limited

Engineering Contradiction:

Improvemorphogen deliveryVSAvoidcontrolled on-demand release

Core Design Contradiction:

Quantity of substanceVSEase of operation

Solution Approach 1:

The patent incorporates enzyme-responsive cleavage sites that detect and respond to specific protease enzymes present at injury sites. This feedback mechanism allows the delivery system to automatically trigger morphogen release when it senses the appropriate biological conditions, achieving on-demand release without external control

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The delivery system performs self-triggered release by utilizing endogenous proteases that are naturally present at tissue injury sites. The system serves itself by using the disease environment's own enzymes to activate release, eliminating the need for external triggering mechanisms

Inventive Principle:

Principle #25Self-service

3Quantity of substance

If non-specific delivery systems are used, then broad distribution is achieved, but targeted delivery to injury sites is reduced

Engineering Contradiction:

Improvebroad distributionVSAvoidtargeted delivery

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent applies local quality by designing the delivery system with spatially differentiated properties: the polymer matrix provides structural integrity throughout the system, while localized enzyme-sensitive peptide sequences are positioned at specific cleavage sites. This allows the system to maintain stability during circulation but selectively release cargo only at the injury site where specific proteases are present

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

This approach provides improved biocompatibility and therapeutically efficacious treatments for applications such as promoting vascularized osteogenesis, while avoiding bioaccumulation issues.

Implementation Method 1

hybrid multifunctional macromers that self-assemble to form nanoparticles

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

enzymes such as proteases by mesenchymal stem cells (MSCs) and endothelial colony forming cells (ECFCs)... cleavage sites responsive to enzymes secreted by mesenchymal stem cells

Methodology Applied

Scientific EffectEnzymatic cleavage: Enzyme

Data Source

PatentUS12208168B2Enzymatically cleavable self-assembled nanoparticles for morphogen delivery

Publication Date: 2025.01.28 UNIVERSITY OF SOUTH CAROLINA

AI summary

The present disclosure is directed to hybrid multifunctional macromers that can self-assemble to form nanoparticles for on-demand and targeted release of morphogens. Embodiments of the disclosure can include the hybrid multifunctional macromers and peptide sequences incorporated therein, self-assembled nanoparticles including the hybrid multifunctional macromers, methods for producing the hybrid multifunctional macromers and peptide sequences, and methods for treating a disease by the on-demand and targeted delivery of a compound using the hybrid multifunctional macromers.