Fibrin Tissue Construct Pre-vascularization

Solution Overview

Problem

Current tissue engineering techniques face challenges in generating functional vascular networks within engineered tissues, leading to ischemia and poor survival rates of transplanted constructs due to inadequate blood supply, especially in thicker tissues where passive diffusion is insufficient.

Innovation Solution

The development of three-dimensional fibrin-based tissue constructs, either alone or in combination with polymeric synthetic scaffolds like PLLA/PLGA, which incorporate vascular cells and tissue-specific cells to form a functional vascular network, utilizing fibrinogen and thrombin to create a supportive matrix for cell growth and vascularization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of stationary object

If passive diffusion is used for nutrient and oxygen delivery in engineered tissues, then thin avascular tissues can be maintained, but thicker tissues suffer from ischemia and poor cell viability

Engineering Contradiction:

Improvetissue thicknessVSAvoidcell viability

Core Design Contradiction:

Length of stationary objectVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-vascularizing the tissue construct before transplantation. Endothelial cells are seeded onto the scaffold and allowed to form vascular networks in vitro prior to implantation. This pre-formed vascular network enables immediate blood flow upon transplantation, preventing ischemia and ensuring cell viability in thicker tissues that would otherwise rely on insufficient passive diffusion.

Inventive Principle:

Principle #10Preliminary action

2Strength

If synthetic scaffolds are used to provide structural support, then mechanical strength is improved, but biological interactions and cell adhesion are insufficient

Engineering Contradiction:

Improvestructural supportVSAvoidbiological interactions

Core Design Contradiction:

StrengthVSAdaptability or versatility

Solution Approach 1:

The patent employs composite materials by combining synthetic scaffold materials (such as PLLA, PLGA, or PCL) with natural extracellular matrix components (such as fibrin, collagen, or gelatin). The synthetic component provides mechanical strength and structural integrity, while the natural component offers biological cues for cell adhesion, proliferation, and differentiation. This composite approach enables the scaffold to simultaneously fulfill mechanical support and biological interaction requirements.

Inventive Principle:

Principle #40Composite materials

3Adaptability or versatility

If natural biomaterials are used to provide biological interactions, then cell adhesion and differentiation are enhanced, but structural support and mechanical stability are reduced

Engineering Contradiction:

Improvebiological interactionsVSAvoidstructural support

Core Design Contradiction:

Adaptability or versatilityVSStrength

Solution Approach 1:

The patent employs composite materials by combining synthetic scaffold materials (such as PLLA, PLGA, or PCL) with natural extracellular matrix components (such as fibrin, collagen, or gelatin). The synthetic component provides mechanical strength and structural integrity, while the natural component offers biological cues for cell adhesion, proliferation, and differentiation. This composite approach enables the scaffold to simultaneously fulfill mechanical support and biological interaction requirements.

Inventive Principle:

Principle #40Composite materials

4Volume of stationary object

If thick three-dimensional constructs are engineered, then complex tissue regeneration is enabled, but media penetration and nutrient delivery to inner regions are insufficient

Engineering Contradiction:

Improveconstruct sizeVSAvoidmedia penetration

Core Design Contradiction:

Volume of stationary objectVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by pre-vascularizing the tissue construct before transplantation. Endothelial cells are seeded onto the scaffold and allowed to form vascular networks in vitro prior to implantation. This pre-formed vascular network enables immediate blood flow upon transplantation, preventing ischemia and ensuring cell viability in thicker tissues that would otherwise rely on insufficient passive diffusion.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent utilizes porous materials by designing scaffolds with controlled porosity and interconnected pore structures. The porous architecture facilitates media penetration and nutrient diffusion throughout the construct volume. When combined with pre-formed vascular networks, the porous structure enables efficient transport of nutrients and oxygen to inner regions of thick constructs, supporting cell survival and tissue regeneration.

Inventive Principle:

Principle #31Porous materials

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

These constructs promote efficient vascularization in vitro and in vivo, enhancing tissue perfusion and survival by integrating with host vasculature, thereby improving the viability and functionality of transplanted tissues.

Implementation Method 1

utilizing fibrinogen and thrombin to create a supportive matrix for cell growth and vascularization

Methodology Applied

Scientific EffectCoagulation: Coagulation

Data Source

PatentUS11045500B2Tissue engineering construct comprising fibrin

Publication Date: 2021.06.29 TECHNION RES & DEV FOUND LTD

AI summary

A three-dimensional fibrin engineered tissue construct is provided selected from: (i) a fibrin gel matrix comprising a combination of tissue-specific cells and at least one type of vascular cells; and (ii) a hybrid scaffold of fibrin gel and a polymeric synthetic scaffold comprising at least one type of vascular cells or a combination of tissue-specific cells and at least one type of vascular cells.