Artificial Tissue Progenitor with Microcapsule Assembly

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Solution Overview

Problem

Current artificial blood vessels face challenges in forming a complete endothelial layer and structured smooth muscle layer, leading to thrombosis and restenosis due to inadequate cell distribution and longevity during in vitro and in vivo seeding processes.

Innovation Solution

A method involving a solid support with attached microcapsules, each containing a cell and biocompatible material, is used to create an artificial tissue progenitor. The microcapsules are assembled into biological constructs using specific adhesion agents, providing mechanical strength and facilitating even cell distribution and integration within the artificial tissue.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If artificial blood vessels are made from traditional materials (metal, glass, polyethylene, silicone rubber), then structural strength is achieved, but thrombus formation occurs in lumens leading to clinical failure

Engineering Contradiction:
Improvestructural strengthVSAvoidthrombus formation
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The invention segments the artificial blood vessel into distinct functional layers: an inner endothelial cell layer (preventing thrombus) and an outer structural layer (providing strength). This is achieved by separately culturing endothelial cells and smooth muscle cells, then assembling them into a multi-layered structure where each layer performs its specific function without interfering with the other.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses composite construction by combining biocompatible materials (for the inner layer that contacts blood) with structurally strong materials (for the outer layer). The inner layer is made from biocompatible substrates that support endothelial cell growth, while the outer layer uses materials providing mechanical strength, creating a composite structure that satisfies both biocompatibility and structural requirements.

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If endothelial cells are directly seeded onto artificial blood vessel surfaces, then thrombosis resistance is improved, but cell distribution is uneven and cells fail to form a complete layer

Engineering Contradiction:
Improvethrombosis resistanceVSAvoidcell distribution uniformity
Core Design Contradiction:
Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

The invention applies preliminary action by pre-culturing endothelial cells on a separate substrate or scaffold before final assembly. This allows cells to proliferate and form a uniform monolayer in a controlled environment, ensuring even distribution before the layer is integrated into the complete artificial blood vessel structure.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention uses an intermediary scaffold or temporary substrate to facilitate uniform cell distribution. Cells are first cultured on this intermediary structure where they can attach and spread evenly, then the intermediary is integrated into the final vessel structure, transferring the uniformly distributed cells to their final position.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Strength

If smooth muscle cells are seeded to form the vascular wall, then structural integrity is improved, but cells rapidly age and lose function after 5-8 passages in vitro

Engineering Contradiction:
Improvestructural integrityVSAvoidcell longevity
Core Design Contradiction:
StrengthVSDuration of action of stationary object

Solution Approach 1:

The invention applies self-service by creating a three-dimensional extracellular matrix environment that mimics the natural vascular wall. This 3D structure provides mechanical support, nutrient diffusion, and signaling cues that promote smooth muscle cell survival, proliferation, and long-term functionality, allowing cells to maintain their properties for extended periods without rapid aging.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention changes the physical parameters of the cell culture environment by transitioning from traditional 2D surfaces to 3D matrices with appropriate stiffness, porosity, and architectural features. These parameter changes create a more physiological microenvironment that extends cell lifespan and maintains function beyond the typical 5-8 passage limit.

Inventive Principle:
Principle #35Parameter changes

4Device complexity

If multiple cell types are seeded simultaneously to form complete tissue structure, then tissue complexity is achieved, but cell arrangement is random and functional layers are not properly formed

Engineering Contradiction:
Improvetissue structure complexityVSAvoidcell layer organization
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The invention segments the tissue construction process into distinct stages and separate cell types. Instead of simultaneous seeding, endothelial cells and smooth muscle cells are cultured, prepared, and assembled separately in a controlled sequence. This ensures that each cell type forms its designated layer with proper organization before integration into the complete tissue structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses dimensional organization by creating distinct spatial layers in the z-dimension. Endothelial cells form an inner luminal layer while smooth muscle cells form an outer wall layer, with each layer having specific thickness and composition. This dimensional arrangement ensures proper functional organization rather than random distribution.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Data Source

PatentUS11439731B2Artificial tissue progenitor and method for preparing the same
Publication Date: 2022.09.13 INNOLIFE CO LTD
  • US11439731B2 patent drawing
  • US11439731B2 patent drawing
  • US11439731B2 patent drawing

AI summary

The invention relates to the technical filed of tissue engineering and 3D printing, particularly relates to an artificial tissue progenitor and a method for preparing the same. In particular, the invention relates to an artificial tissue progenitor comprising a solid support and a plurality of microcapsules, wherein at least one microcapsule is attached to the solid support, and the microcapsule comprises a cell and a biocompatible material encapsulating the cell, to a method for preparing the artificial tissue progenitor, to a kit and a package useful for preparing the artificial tissue progenitor, to an artificial tissue obtained by culturing the artificial tissue progenitor, such as an artificial lumen, to a lumen implant or a lumen model containing the artificial tissue progenitor or the artificial lumen, to use of the artificial tissue progenitor in the manufacture of an artificial tissue, a lumen implant or a lumen model, and to use of the artificial tissue in the manufacture of a lumen implant or lumen model.