Vascularized In Vitro Perfusion Device With Adaptive Microcirculation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current in vitro microcirculation systems lack stability and adaptability, failing to recapitulate the complex structure and function of native microvasculature, which is essential for effective tissue perfusion and vascular remodeling, limiting their utility in biomedical research and tissue engineering applications.
Innovation Solution
A vascularized in vitro perfusion device is developed, featuring a network of endothelial cell-lined channels integrated with native, intact microvasculature, where endothelial sprouts from the channels inoscule with native microvessels to form a stable and adaptable microcirculation, capable of responding to hemodynamic and environmental stimuli.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pre-formed channels are lined with vascular cells to create microvascular networks, then a perfusable vascular system is established, but the system lacks adaptability to hemodynamic changes and parenchyma requirements
Solution Approach 1:
The patent transitions from static pre-formed channels to dynamic self-assembling microvessels. The microvessels are constructed from multiple cell types including endothelial cells, pericytes, and smooth muscle cells that can dynamically remodel and adapt their structure in response to hemodynamic forces and tissue metabolic needs, enabling the vascular network to change its topology and dimensions adaptively
Solution Approach 2:
The system employs self-organizing properties of vascular cells to automatically form functional microvascular networks without requiring pre-defined channel geometries. The cells autonomously assemble into tube structures with appropriate luminal dimensions and wall compositions based on local biochemical and mechanical cues, enabling the system to self-adapt to varying tissue requirements
2Adaptability or versatility
If a complex multi-cellular vascular system is created to achieve physiological adaptability, then the system better recapitulates native microcirculation, but the device complexity increases
Solution Approach 1:
The patent combines multiple cell types (endothelial cells, pericytes, smooth muscle cells) and extracellular matrix components into an integrated microvessel construct that functions as a unified adaptive system. This merging of cellular components allows the vascular network to exhibit emergent physiological properties including hemodynamic sensing, remodeling, and adaptation that cannot be achieved by single cell types alone
Solution Approach 2:
The system utilizes changes in physical and biochemical parameters (shear stress, oxygen tension, growth factors) to regulate microvessel assembly, maturation, and remodeling. These parameter changes enable the complex multi-cellular system to dynamically adjust its structure and function in response to physiological conditions without requiring external control mechanisms
Data Source
Figure 1
Figure 2
Figure 3
AI summary
A bona fide adaptable in vitro microcirculation model is provided by integrating a 3-D printed network of endothelial-cell lined perfusion channels, formed via sacrificial casting in a gel matrix, with a native, adaptable microvasculature matured from native microvessels added to the gel matrix. Responsive vascular adaptation exhibited by the in vitro microcirculation is physiologically relevant. Methods for fabricating, devices, models and investigative platforms for pharmaceutical applications, vascular mechanism and microvessel-parenchyma interaction studies, and vascularizing strategies for tissue engineering applications are also disclosed.