Bioengineered Gut-Sphincter Complexes via Segmented Cell Culture
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Solution Overview
Problem
There is a need for functional tissue-engineered sphincteric constructs for repair and reconstruction of damaged sphincters and tissue-engineered gut-sphincter complexes for therapeutic interventions, as well as in vitro models for drug testing and development of therapies, due to the challenges in preserving sphincter integrity and motility in neuro-muscular disorders.
Innovation Solution
Three-dimensional bioengineered tubular gut-sphincter complexes are created by obtaining intestinal and sphincteric smooth muscle cells, along with enteric neural progenitor cells, and culturing them on specific molds and scaffolds to form innervated tissue constructs that can be unified and further cultured to achieve functional gut-sphincter complexes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tissue-engineered sphincteric constructs are created to repair damaged sphincters, then sphincter integrity and motility can be restored, but the complexity of creating functional neuro-muscular tissue increases significantly
Solution Approach 1:
The tissue engineering process is divided into distinct segments: obtaining smooth muscle cells from intestinal or sphincteric sources, culturing them on specific molds to achieve desired geometry, adding neural progenitor cells for innervation, and maturing the constructs in bioreactors. This segmentation makes the complex process more manageable and scalable.
Solution Approach 2:
Smooth muscle cells are cultured on molds with specific surface textures beforehand to induce alignment and establish the basic tissue structure before neural progenitor cells are added. This preliminary structuring ensures proper tissue architecture is formed prior to neural integration, simplifying the overall construction process.
2Adaptability or versatility
If three-dimensional tubular gut-sphincter complexes are engineered with multiple cell types, then physiological functionality is improved, but the manufacturing process becomes more complex
Solution Approach 1:
The patent combines multiple cell types (intestinal smooth muscle cells, sphincteric smooth muscle cells, and enteric neural progenitor cells) into unified three-dimensional tubular constructs. These merged constructs exhibit coordinated physiological functions including peristalsis and sphincteric control, achieving versatility that mirrors native gut-sphincter complexes.
Solution Approach 2:
Biocompatible gels serve as intermediary materials that facilitate the integration of different cell types within the three-dimensional constructs. These gel matrices provide a supportive environment that enables smooth muscle cells and neural progenitor cells to coexist and interact, simplifying the manufacturing of multi-cellular constructs.
3Stability of the object's composition
If smooth muscle cells are aligned on molds with specific surface textures, then tissue organization and functionality are improved, but the manufacturing precision requirements increase
Solution Approach 1:
The molds with specific surface textures enable smooth muscle cells to self-align through contact guidance during culture. The surface topography naturally directs cell orientation without requiring external manipulation or high-precision positioning equipment, reducing manufacturing precision requirements while achieving organized tissue structure.
4Adaptability or versatility
If innervated tissue constructs are created by adding neural progenitor cells, then physiological responsiveness is improved, but the complexity of culturing and integrating multiple cell types increases
Solution Approach 1:
Neural progenitor cells are added to already-established smooth muscle tissue constructs rather than attempting to co-culture all cell types simultaneously. This sequential approach allows the smooth muscle framework to mature first, providing a stable substrate for neural integration and reducing overall culture complexity.
Data Source
AI summary
Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post. This innervated sphincter construct can also be transferred to the tubular scaffold such that the intestinal tissue construct and sphincter construct contact each other, and the resulting combined sphincter and intestinal tissue constructs can be further cultured about the scaffold until a unified tubular gut-sphincter complex is obtained.