In Situ Expanding Tissue Seed for Organ Regeneration
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Solution Overview
Problem
Scaling up engineered tissues to physiologically-relevant sizes, particularly for large solid organs like the heart, kidney, and liver, is challenging due to the need for robust vascularization to deliver nutrients effectively.
Innovation Solution
An engineered human tissue seed comprising human hepatocytes, endothelial cells, and fibroblasts in a degradable hydrogel scaffold that expands in situ in response to systemic regenerative cues, forming a vascularized tissue structure resembling native liver architecture without fibrosis or rejection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If engineered tissues are scaled up to physiologically-relevant sizes, then the tissue can serve as a functional organ replacement, but robust vascularization becomes increasingly difficult to achieve
Solution Approach 1:
The patent pre-organizes endothelial cells into cord-like structures within the hydrogel scaffold before implantation. These pre-formed vascular templates are positioned to guide subsequent vascular invasion and growth, ensuring that blood vessels can efficiently reach all regions of the expanded tissue even at large scales
Solution Approach 2:
The patent uses a degradable hydrogel scaffold as an intermediary structure that temporarily supports the engineered tissue during expansion. The scaffold provides mechanical support and guides vascularization, then degrades over time as the tissue becomes self-sufficient, resolving the contradiction between achieving large size and maintaining reliable vascularization
2Volume of moving object
If the engineered tissue seed expands significantly in situ, then functional organ mass is achieved, but control over expansion and structural organization becomes more difficult
Solution Approach 1:
The patent creates regions of different cell types and densities within the hydrogel scaffold, with parenchymal cells organized in specific zones and endothelial cords positioned in vascular regions. This local differentiation maintains structural organization during expansion, as each region responds appropriately to regenerative cues while preserving overall architecture
Solution Approach 2:
The patent utilizes changes in the physical and chemical parameters of the hydrogel scaffold, including its degradability and mechanical properties, to control tissue expansion. The scaffold's gradual degradation releases cells in a controlled manner, enabling predictable expansion while maintaining structural organization through the scaffold's remaining framework
3Reliability
If multiple cell types are organized in specific architectures, then functional tissue structures form, but device complexity increases
Solution Approach 1:
The patent divides the engineered tissue into distinct functional segments: parenchymal cell aggregates for metabolic functions and endothelial cell cords for vascularization. This segmentation allows each cell type to be optimized for its specific function while simplifying the overall organization, as the segments self-assemble into functional structures without requiring complex pre-arranged architectures
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
The engineered tissue seed expands up to 50-fold, forming perfused vascular networks, bile ducts, and secreting hepatocyte blood products, achieving functional liver tissue with enhanced drug metabolism and vascularization, thus addressing the challenge of scaling up solid organs.
Implementation Method 1
human hepatocytes, endothelial cells, and fibroblasts in a degradable hydrogel scaffold that expands in situ in response to systemic regenerative cues
Data Source
AI summary
Engineered human tissue seed construct are provided that are suitable for implantation in subjects. Methods of making and using the engineered tissue seed constructs are provided.