Fibrin-Binding Microgels for Hemostasis

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Solution Overview

Problem

Current hemostasis technologies, including topical sealants and synthetic analogues of clotting constituents, fail to fully recapitulate the natural hemostasis system's functions such as fibrin clot formation, contraction, and cytokine release, especially in dynamic flow conditions, leading to inadequate wound management in traumas.

Innovation Solution

Development of ultra-low crosslinked microgels, referred to as Platelet-like Particles (PLPs), which are conjugated with fibrin-binding moieties, allowing for selective binding to fibrin, stabilizing, and enhancing clot formation, while promoting clot contraction and wound healing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If current hemostasis technologies (topical sealants, synthetic analogues) are used, then clotting time is reduced, but the ability to fully recapitulate natural platelet functions (fibrin clot formation, contraction, cytokine release) is lost

Engineering Contradiction:

Improveclotting timeVSAvoidhemostasis effectiveness

Core Design Contradiction:

Loss of timeVSReliability

Solution Approach 1:

The patent creates artificial platelets that copy the structure and function of natural platelets by displaying platelet-specific surface proteins (GPIb, GPIIb/IIIa, P-selectin) on a synthetic microgel core. This copying approach enables the artificial platelets to perform multiple natural platelet functions including fibrin clot formation, clot contraction, and cytokine release, while maintaining rapid clotting response.

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The artificial platelet design integrates multiple hemostatic functions into a single platform. The microgel core provides structural support and deformability, surface proteins enable fibrin binding and platelet recruitment, and embedded cytokines promote wound healing. This multi-functional design resolves the contradiction by achieving both rapid clotting and comprehensive hemostatic effectiveness.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Strength

If multivalent display of platelet-binding motifs is used on micro/nano-sized vehicles, then binding and augmentation of clot formation is achieved, but the ability to deform within and in response to the fibrin mesh is lost

Engineering Contradiction:

Improveclot formation augmentationVSAvoiddeformability

Core Design Contradiction:

StrengthVSAdaptability or versatility

Solution Approach 1:

The patent optimizes the physical parameters of the microgel core, specifically controlling particle size (1-10 μm) and crosslinking density to achieve optimal deformability. The microgel's soft, flexible structure allows it to deform and spread within the fibrin mesh, mimicking natural platelet behavior, while maintaining sufficient structural integrity for clot formation augmentation.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If freeze-dried harvested native platelets are used, then natural platelet functions are preserved, but device complexity and manufacturing difficulty increase

Engineering Contradiction:

Improvenatural platelet function preservationVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs a synthetic microgel-based platform that can be manufactured through standardized chemical processes rather than complex biological harvesting and freeze-drying. This approach creates a disposable, pre-packaged artificial platelet product that eliminates the need for platelet harvesting, processing, and storage infrastructure, significantly simplifying manufacturing while maintaining functional reliability.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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

PLPs effectively reduce bleeding time, enhance fibrin clot density, and induce clot contraction, mimicking natural platelet functions, thereby improving hemostasis and wound healing outcomes.

Implementation Method 1

microgels containing fibrin binding moieties... binding, stabilization and enhancement of fibrin clot formation

Methodology Applied

Scientific EffectFibrin binding: Adsorption

Implementation Method 2

clot contraction... The composition also induces or promotes clot contraction in the subject

Methodology Applied

Scientific EffectClot contraction: Mechanical Force

Data Source

PatentUS11419948B2Functionalized microgels with fibrin binding elements

Publication Date: 2022.08.23 GEORGIA TECH RES CORP

AI summary

Ultra-low crosslinked microgels made of an ultra-low crosslinked polymer are provided. The microgels, also referred to as Platelet-like Particles (PLPs), preferably have <0.5% crosslinking densities. One or more of the polymers are conjugated with a fibrin-binding element or moiety, preferably H6, in an amount effective to confer to the microgel selective binding to fibrin under physiological conditions. The PLPs can recapitulate multiple key functions of platelets including binding, stabilizing and enhancing fibrin clot formation, responsiveness to injury cues, and induction of clot contraction. In a preferred embodiment, the microgel or PLP has little or no binding to soluble fibrinogen under physiological conditions compared to its binding to fibrin. The microgels or PLPs are prepared using crosslinker-free synthesis conditions, and can promote or induce clotting and clot contraction.