EMT-Primed Microtissue Hydrogel for Scar-Free Wound Healing

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Solution Overview

Problem

Current tissue engineering approaches, including the use of scaffolds and stem cell therapies, have been less successful in harnessing self-organizing processes during embryonic development to create complex biological structures in vitro and promoting regenerative and scar-free healing, as they often result in marginal or variable healing outcomes.

Innovation Solution

A method involving EMT-priming of cells to form microtissue compositions, such as toroids, within a three-dimensional hydrogel structure, using a polypeptide with the carboxy-terminal amino acid sequence of alpha Connexin or its conservative variant, to stimulate epithelial-mesenchymal transition (EMT) and promote healing and tissue regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional scaffold-based tissue engineering or organ printing is used, then structural frameworks can be provided for cell growth, but the ability to accurately recapitulate naturally occurring complexities of shape, internal structure and functionality is limited

Engineering Contradiction:
Improvestructural complexityVSAvoidscaffold structure
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies self-service by enabling cells to autonomously self-organize and self-assemble into complex three-dimensional structures without requiring pre-designed scaffolds. The cells inherently possess the capacity to form organized tissues through their natural biological behaviors, eliminating the need for complex external structural frameworks

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention extracts and removes the scaffold component from the tissue engineering system. By eliminating the scaffold entirely and relying solely on cell-intrinsic self-organizing capabilities, the patent simplifies the system architecture while maintaining or enhancing structural complexity through biological self-assembly

Inventive Principle:
Principle #2Taking out (Extraction)

2Reliability

If dispersed stem cells are introduced into a diseased organ, then regenerative therapy can be provided, but the healing outcomes are marginal, variable, or controversial with little regard for the status of randomly introduced cells

Engineering Contradiction:
Improvehealing outcomeVSAvoidcell introduction method
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-forming cells into organized three-dimensional microtissue structures in vitro before transplantation. These pre-organized cell aggregates possess inherent structural and functional characteristics that prepare them for effective integration into the target tissue, rather than introducing random dispersed cells

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention segments the cell population into discrete, standardized three-dimensional microtissue units with controlled size and composition. This segmentation allows for consistent dosing and predictable behavior during transplantation, improving reliability while simplifying the transplantation procedure

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS8815556B2Compositions and methods for tissue engineering, tissue regeneration and wound healing
Publication Date: 2014.08.26 MUSC FOUNDATION FOR RESEARCH DEVELOPMENT(US)
  • US8815556B2 patent drawing
  • US8815556B2 patent drawing
  • US8815556B2 patent drawing

AI summary

In accordance with certain embodiments of the present disclosure, a kit is described. The kit includes primed living cells joined to and at least partially within a three-dimensional hydrogel structure and an isolated polypeptide having the carboxy-terminal amino acid sequence of an alpha Connexin, or a conservative variant thereof, wherein the polypeptide does not include the full length alpha Connexin protein.