Implantation Device for Ex Vivo Bone Marrow Culture
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Solution Overview
Problem
Current tissue engineering and in vitro tissue growth strategies face challenges in recapitulating the natural structures and functions of tissues and organs due to the difficulty in achieving a balance of growth factors, signaling molecules, nutrients, and mechanical forces, leading to inefficient long-term engraftment and host hematopoietic reconstitution of hematopoietic stem cells.
Innovation Solution
An implantation device with cell growth chambers and microfluidic channels is implanted in vivo, containing bone-inducing materials like demineralized bone powder and BMPs, allowing connective tissues and mesenchymal stem cells to grow and form bone marrow, which can be surgically removed and maintained ex vivo through perfusion with media and gases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If hematopoietic stem cells are cultured in vitro to expand therapeutic bone marrow material, then cell production capacity is improved, but long-term engraftment and host hematopoietic reconstitution efficiency deteriorates
Solution Approach 1:
The patent uses an implantation device as an intermediary structure that provides a controlled microenvironment for stem cell culture. The device contains bone-inducing materials and growth factors that mediate between the stem cells and the host environment, enabling proper tissue organization and maintenance of stem cell features during ex vivo expansion
Solution Approach 2:
The implantation device creates localized zones with specific biochemical and mechanical properties within the host animal. Different regions of the device contain specific growth factors, extracellular matrix components, and structural elements that provide tailored microenvironments for different cell types and functions
2Adaptability or versatility
If tissue or organ structures are removed from a subject for ex vivo study or propagation, then research and therapeutic application capability is improved, but tissue damage and difficulty in reestablishing proper nutrient flow deteriorates
Solution Approach 1:
The implantation device is pre-loaded with bone-inducing materials, extracellular matrix scaffolds, and growth factors before implantation. This preliminary preparation ensures that the proper microenvironment and nutrient flow pathways are established before tissue growth occurs, preventing damage that would result from attempting to reestablish these conditions after tissue removal
Solution Approach 2:
The device enables tissues to self-organize and self-sustain within the controlled microenvironment. The extracellular matrix scaffolds and growth factors within the device support autonomous tissue development and maintenance of physiological functions, reducing the need for external intervention and minimizing damage during ex vivo propagation
3Manufacturing precision
If a complex mixture of growth factors, signaling molecules, nutrients, and mechanical forces is provided to grow tissues in vitro, then tissue structure formation is improved, but system complexity and difficulty in achieving proper balance deteriorates
Solution Approach 1:
The implantation device merges multiple functions into a single integrated structure. The extracellular matrix scaffolds, growth factor reservoirs, mechanical support elements, and nutrient delivery systems are combined into one device that can be implanted as a single unit, simplifying the overall system while maintaining the complex microenvironment needed for tissue formation
Solution Approach 2:
The device components work autonomously to maintain the complex mixture of growth factors, signaling molecules, and nutrients. The extracellular matrix scaffolds self-assemble, growth factors are released in controlled sequences, and mechanical forces are generated through the device structure itself, reducing the need for external control systems
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 device enables the formation of functional bone marrow and tissue structures that closely mimic in vivo conditions, allowing for the study and production of therapeutic cells and tissues, and can be used for transplantation and research.
Implementation Method 1
The implantation device contains compounds which induce the growth of the desired tissue type or types in a chamber that has one or more corresponding cell growth chamber openings (e.g. ports) to the surrounding tissue space. By way of example, in order to induce the growth of bone, the implantation device can contain bone-inducing materials, i.e. demineralized bone powder and/or bone morphogenic proteins (BMPs).
Implementation Method 2
The cell, tissues, and/or organoids that formed and/or developed in the implantation device can be maintained as viable in vitro by perfusing the cell, tissues, and/or organoids with media and/or gases necessary for cell survival within the implantation device or after being removed from the implantation device and placed in a microfluidic device.
Implementation Method 3
As a result of wound healing, connective tissues containing microcapillaries and mesenchymal stem cells can grow into the cell growth chamber of the implantation device and, due to the presence of the bone-inducing material, can form bone with spaces that recruit circulating hematopoietic precursor cells to form fully functional bone marrow.
Data Source
Figure 1A~1B
Figure 1C
Figure 2A~2B
AI summary
The technology described herein is directed to methods and devices that can be used to induce functional organ structures to form within an implantation device by implanting it in vivo within the body of a living animal, and allowing cells and tissues to impregnate the implantation device and establish normal microenvironmental architecture and tissue-tissue interfaces. Then the contained cells and tissues can be surgically removed intact and either transplanted into another animal or maintained ex vivo by perfusing it through one or more of the fluid channels with medium and/or gases necessary for cell survival.