The disclosure relates to a tissue regeneration, growth, and/or treatment device comprising an in-vivo bioreactor systems and methods for tissue engineering within a living creature.
There is a great need for the ability to replace organs and tissues in living creatures due to injury and disease. Unfortunately replacement organs, and tissue are not readily available, and immunosuppression drugs required for transplants have considerable side-effects. Scientists have developed external bioreactor systems where cells, tissue, or organs can grow. However, it has proven difficult to transplant these cells, tissues, or organs into living creatures due to the lack of vasculature. Secondly, there currently exist a number of biological wound care products that have practicality and feasibility issues. These include accellular and cellular dermal matrices, growth factors, and cell transplant technology. As a result there is a large need for improvement of existing technologies or methods to improve the outcomes of their use. To overcome these issues, scientists have begun working on in-vivo bioreactor systems in which the bioreactor system is implanted into the living creature. There have been many issues with these in-vivo bioreactor systems such as: the difficulty in not being able to visualize the growing tissues, or organs; the difficulty in determining properties of the growing tissue, or organs and its surrounding environment; the difficulty in delivering fluids, such as mediums or other agents, to the growing/regenerating tissue or organ to help it grow; the difficulty in applying stimuli to the growing tissue or organ to help it grow; the difficulty in accessing the growing tissue or organ; the inability to vary, adapt, or change-out the in-vivo bioreactor system to obtain varying functions for the growing tissue or organ after the in-vivo bioreactor system is implanted; the difficulty in adding sequential cell populations in different layers/configurations to generate tissue or an organ; and additional issues.
There is a need for an in-vivo bioreactor system which will resolve one or more of the issues associated with the current systems.
In one embodiment, an in-vivo bioreactor system includes a base, a chamber, an access member, an inlet port, an outlet port, and a transparent viewing member. The base includes an internal base cavity. The chamber attaches and detaches from the base. The chamber includes an internal chamber cavity which is in communication with the internal base cavity when the chamber is attached to the base. The access member when disposed in an open position allows access to the internal base cavity or the internal chamber cavity from outside the in-vivo bioreactor system. The inlet port is in communication with the internal base cavity or the internal chamber cavity. The outlet port is in communication with the internal base cavity or the internal chamber cavity. The transparent viewing member allows viewing of the internal base cavity or the internal chamber cavity from outside the in-vivo bioreactor system.
In another embodiment, an in-vivo bioreactor system attached to a living creature includes a base, a chamber, an access member, an inlet port, an outlet port, and a transparent viewing member. The base includes an internal base cavity. The base is attached to the living creature with a portion of the base disposed underneath a dermis of the living creature. The chamber is attached to the base. The chamber includes an internal chamber cavity which is in communication with the internal base cavity. The access member is attached to the chamber. When the access member is disposed in an open position access is provided to the internal base cavity or the internal chamber cavity from outside skin of the living creature. The inlet port is in communication with the internal base cavity or the internal chamber cavity. The outlet port is in communication with the internal base cavity or the internal chamber cavity. The transparent viewing member allows viewing of the internal base cavity or the internal chamber cavity from outside the skin of the living creature.
In an additional embodiment, a method of using an in-vivo bioreactor system is disclosed. In one step, a base of an in-vivo bioreactor system is located to be at least partially disposed below a dermis of the living creature. In another step, a chamber of the in-vivo bioreactor system is attached to the base so that an internal chamber cavity of the chamber is in communication with an internal base cavity of the base. In an additional step, a medium is flowed through an inlet port of the in-vivo bioreactor system into the internal base cavity or the internal chamber cavity while the chamber is attached to the base attached to the living creature. In still another step, a tissue or an organ is grown within the internal base cavity or the internal chamber cavity. In yet another step, the growing tissue or the growing organ disposed within the internal base cavity or the internal chamber cavity is viewed through a transparent viewing member of the in-vivo bioreactor system
These and other features, aspects and advantages of the disclosure will become better understood with reference to the following drawings, description and claims.
The following detailed description is of the best currently contemplated modes of carrying out the disclosure. The description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the disclosure, since the scope of the disclosure is best defined by the appended claims.
The base 12 is made of a biocompatible material such as but not limited to: silicone, thermoplastic elastomers, polypropylene, titanium watershed XC 11122, or other types of biocompatible materials. In other embodiments, the base 12 may be of varying shapes, sizes, type, or materials. The base 12 is designed to not only anchor the chamber 14 of
The chamber 14 is made of biocompatible material such as but not limited to: silicone, thermoplastic elastomers, polypropylene, titanium, watershed XC 11122, or other types of biocompatible materials. An inner diameter 55 of the chamber 14 accommodates different matrices, sensors, and nutrients to allow the chamber 14 to be used for numerous applications. In other embodiments, the chamber 14 may be of varying shapes, sizes, type, or materials. The chamber 14 is implantable and designed to be in contact with tissues and blood vessels to provide the vascular network essential to grow complex, 3-dimensional tissues or organs. The chamber 14 is designed to contain matrices of any biocompatible type, or engineered or micropatterned scaffolds (including decellularized tissues or imprinted templates for tissue growth). The chamber 14 is flexible and can work with any biocompatible matrix or engineered system that can be implanted in-vivo.
The access member 16 is made of biocompatible materials such as but not limited to: silicone, thermoplastic elastomers, polypropylene, titanium, watershed XC 11122, or other types of biocompatible materials. In other embodiments, the access member 16 may be of varying shapes, sizes, type, or materials. As discussed more thoroughly below, the access member 16 is configured to, when attached to the chamber 14 of
In this attached configuration, the transparent viewing member 68 allows viewing of the internal base cavity 28, the internal chamber cavity 42, and the internal access member cavity 60 from outside the in-vivo bioreactor system 10 and from outside the skin of the dermis 72 of the living creature 74. This allows viewing of the substance 78 disposed within the internal base cavity 28 and the internal chamber cavity 42 so that it can be determined how well the substance 78 is growing to create a tissue or an organ. In this attached configuration access to the internal base cavity 28, the internal chamber cavity 42, and the internal access member cavity 60 is closed from outside skin of the dermis 72 and is closed from a side 10a and above 10b the in-vivo bioreactor system 10 with the exception of through the inlet and outlet ports 52 and 54. A medium 80 has been flowed from external system 75 through the inlet port 52, through the internal chamber cavity 42, and into internal base cavity 28. The external system 75 comprises a perfusion system (which may include a perfusion pump) for delivering and regulating the medium 80 to the inlet port 52. The medium 80 comprises a growth factor, a protein, a nutrient, a cell, a liquid scaffold, a medication, a treatment, or another type of medium for assisting the substance 78 to grow to create a tissue, or an organ within the living creature 74. The outlet port 54 may be used to suction out the medium 80 from within the internal base cavity 28 and the internal chamber cavity 42 to external system 77. External system 77 comprises an external monitoring device which monitors and analyzes the medium 80 or tissue or organ material as it's suctioned out using sensors 79 in order to monitor in real-time the tissue or organ and the tissue growth/regeneration. The sensors 79 may detect oxygen, pH, temperature, glucose, protein, metabolite, flow, biological product, or other items. Collectively, the inlet and outlet ports 52 and 54, using the external systems 75 and 77, may be used to deliver and regulate mediums 80, to provide suction for aspiration or as a vacuum, to monitor and analyze the tissue or organ and the tissue growth/regeneration, or for other purposes. Through inlet and outlet ports 52 and 54 any number of therapeutics, reagents, nutrients, growth factors, liquid scaffolds, medications, treatments, or other mediums may be administered in a manual or automated fashion (controlled perfusion rate) to aid tissue or organ healing and tissue growth/regeneration. In other embodiments, any number of external systems of varying type may be connected to the inlet and/or outlet ports 52 and 54 of the bioreactor system 10.
In this attached configuration the sensor 70 disposed within or adjacent to the internal base cavity 28, the internal chamber cavity 42, or the internal access member cavity 60 is disposed against or adjacent to the substance 78. In such manner, the sensor 70 may be used to take various sensor measurements to determine the conditions in which the substance 78 is growing, to determine how well the substance 78 is growing, or to take other sensor measurements to make other determinations. In this attached configuration, the stimuli member 36 disposed within or adjacent to the internal base cavity 28, the internal chamber cavity 42, or the internal access member cavity 60 is disposed against or adjacent to the substance 78 applying stimulation, powered by member 38 (only partially shown for ease of illustration), to assist in creating and growing a tissue or organ.
Each of the varying chambers 14a, 14b, and 14c may have an internal chamber cavity 42a, 42b, and 42c which will be in communication with the internal base cavity 28 (shown in
In step 92, a medium is flowed through an inlet port of the in-vivo bioreactor system into the internal base cavity or the internal chamber cavity while the chamber is attached to the base attached to the living creature. Step 92 may comprise an external system (such as an external pump) delivering the medium to the inlet port. In step 94, the medium is flowed from the internal base cavity or the internal chamber through an outlet port of the in-vivo bioreactor system. The medium comprises a growth factor, protein, nutrient, a liquid scaffold, a medication, a treatment, or another medium, and may or may not contain cells, or another medium for assisting the biocompatible matrix, the biocompatible scaffold, the decellularized matrix, or the other biocompatible engineered system disposed within the internal base cavity or the internal chamber to be created and grow into a tissue or an organ. In step 96, a tissue or an organ is created and grown within the internal base cavity or the internal chamber cavity from the biocompatible matrix, the biocompatible scaffold, the decellularized matrix, or the other biocompatible engineered system. In step 98, stimulation is applied to the growing tissue, or the growing organ disposed within the internal base cavity or the internal chamber cavity using a stimuli member of the in-vivo bioreactor system. The stimulation being applied may comprise a tension or compression stress or strain, electrical stimulation, or another type of stimulation.
In step 100, a property within the internal base cavity or the internal chamber cavity is sensed using a sensor or an array of sensors of the in-vivo bioreactor system. The sensed property may comprise a temperature, a pH, an oxygen level, a flow, a protein, a glucose, a biological product such as cytokines, growth factors, metabolites, or another property which may be useful to know in growing the biocompatible matrix, the biocompatible scaffold, the decellularized matrix, or the other biocompatible engineered system into a tissue or an organ. In another embodiment, step 100 may comprise an external system sensing the property by testing the medium or a material of the tissue or organ after it exits (such as through suction) the in-vivo bioreactor system. In step 102, the growing tissue, or the growing organ disposed within the internal base cavity or the internal chamber cavity is viewed through a transparent viewing member of the in-vivo bioreactor system.
In step 104, after the chamber has been used to achieve a first function for the growing tissue or the growing organ, the access member is detached from the chamber, the chamber is detached from the base, a varied chamber is attached to the base to dispose an internal chamber cavity of the varied chamber in communication with the internal base cavity, and the access member is attached to the varied chamber. The varied chamber may vary from the original chamber in size, structure, number or type of inlet or outlet ports, number or type of sensors or sensor arrays, or may vary in another way. In step 106, the varied chamber attached to both the base and the access member is used to achieve a second function for the growing tissue, or the growing organ. The first and second functions of the varied chambers may comprise growing or obtaining varied properties, growth levels, growth stages, or results for the created and growing tissue, or the created and growing organ. In other embodiments, the first and second functions may vary. One or more external systems may be connected to the varied chambers to achieve and/or monitor the first and second functions.
One or more embodiments of the disclosure may reduce one or more problems associated with one or more of the existing in-vivo bioreactor systems and methods. For instance, the placement of the in-vivo bioreactor system within a living creature provides the vascular network necessary for tissues and complex tissues, such as organs to be engineered in-situ ad long-term. The modularity of the in-vivo bioreactor system, including the ports, allows for mediums to be intermittently or continuously delivered such as but not limited to growth factors, nutrients, therapeutics, cells, chemicals, liquid scaffolds, medications, treatments, or matrices in order to both enhance tissue growth as well as direct and orchestrate cellular depositions/organization. The adaptability of the chamber extends its utility beyond solely the delivery of mediums, in that it also provides the opportunity of incorporating sensors in isolation or in arrays that can measure variables including but not limited to oxygen, flow, pH, temperature, glucose, protein, and can provide biological products like cytokines, growth factors, metabolites, or other substances in order to monitor and track any changes in the tissue regeneration process. Moreover, one or more external systems may be connected to the in-vivo bioreactor system to deliver, monitor, analyze, and regulate the medium or a material of the tissue or organ to analyze, control, and regulate the tissue or organ and the tissue growth/regeneration.
The adaptable nature of the device further permits incorporation of a variety of matrices and growth of tissue in a controllable manner, including but not limited to tissue printing, stretching, and other interventions that can influence the growth of tissue in a manner responsive to a wide variety of stimuli, such as mechanical, electrical, chemical, or other types of stimuli. These stimuli can be built into different varying modular chambers, and may range from morphogenic cues, to stretch/strain and other mechanoresponsive stimuli, to flow or negative pressure stimuli, or other stimuli. The modular, adaptable chamber permits the sequential addition of different cell populations in different layers/configurations to generate biomimetic tissue and organs. Different modules may be used according to the discrete needs of the growing tissue. The transparent viewing member and the removable access member allow for access to and viewing of the growing tissue, or organ. The in-vivo bioreactor systems and methods of the disclosure may be used for tissue engineering, angiogenesis, lymphangiogenesis, cellular proliferation, and for other uses.
It should be understood, of course, that the foregoing relates to exemplary embodiments of the disclosure and that modifications may be made without departing from the spirit and scope of the disclosure as set forth in the following claims.
The present application claims the benefit of U.S. Provisional Patent Application No. 61/674,681, filed Jul. 23, 2012. The content of this U.S. Provisional Patent Application is hereby incorporated by reference in its entirety.
This invention was made with government support under Grant No. W81XWH-11-1-0839 awarded by the US Army Medical Research and Materiel Command (Army/MRMC). The government has certain rights in the invention.
Number | Date | Country | |
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61674681 | Jul 2012 | US |