News Column

"Semipermeable Medical Pouches and Their Uses" in Patent Application Approval Process

August 25, 2014

By a News Reporter-Staff News Editor at Diabetes Week -- A patent application by the inventor Gatenholm, Erik (Blacksburg, VA), filed on August 29, 2013, was made available online on August 14, 2014, according to news reporting originating from Washington, D.C., by NewsRx correspondents (see also Patents).

This patent application has not been assigned to a company or institution.

The following quote was obtained by the news editors from the background information supplied by the inventors: "The present innovation relates to the field of medical devices, tissue engineering, regenerative medicine, and cell therapy, more particularly, to systems and methods for production by bacteria of nanocellulose medical devices in the form of pouches with tubing which allow cell injection and media exchange.

"Regenerative strategies using autologous or stem cells for many diseases are limited by poor cellular survival, distribution and integration after transplantation into the host body. What is needed are suitable biomaterials which can act as compartment-packaging and a delivery system at the same time. In addition, such packaging should be very functional and act rather as a bioreactor for the selected cells. It should allow cells to migrate, proliferate and differentiate. It should keep nutrients which cells need but allow waste products of cell metabolism to be released. It should also allow oxygen transport into the bioreactor and carbon dioxide out of the bioreactor. If cells are indented to be used for cell therapy, the bioreactor should allow diffusion of components such as insulin (or other drugs or substances) out from bioreactor. If the cells from another patient or from another species (xenotransplantation) are used the bioreactor should have the ability to provide immunoisolation.

"The current art of biomaterials provides shaped cellulose tubes (hollow) with limited thickness, which have been produced in the method using tubular bioreactor as described in WO2001061026. Oxygen delivery through the silicon support has been explored for manufacturing of tubes for applications such as vascular grafts as described in EP2079845 and WO2008040729 A2.

"This invention describes an ultimate solution for all these challenges, specifically, a nanocellulose pouch grown by bacteria in a silicone template. This unique biomaterial behaves like hydrogel and shows diffusion properties which qualify it for the mentioned purposes. At the same time the pouch has good mechanical properties for long term storage of cells."

In addition to the background information obtained for this patent application, NewsRx journalists also obtained the inventor's summary information for this patent application: "A biofabrication process is provided in which bacteria suspension in media is injected into a gas permeable pouch mold with attached tubing and then cultivated for 1-5 days. The process involves growth of pouches in molds with tubing with diameter smaller than 5 mm. The preferential material used for the mold is an oxygen permeable thin silicone mold in the shape of a pouch. In this process the bacteria suspension in growth medium is injected into the silicone mold and the nanocellulose pouch is produced by the bacteria during the 1-5 days.

"The hydrogel-like pouches, after removal of bacteria by washing with alkali, and then with de-ionized water can then be processed in different ways. One way is to dehydrate the pouch by freeze drying or solvent exchange and then introduce another component in water solution such as a growth factor, another polymer, drugs, conductive polymers or antibacterial agents. If desired, then cells can be injected. In embodiments, the added component, such as cells, is able to slow release out of the BNC Pouch. In embodiments, the pouch walls are porous to allow diffusion of certain sized molecules yet containment of larger sized molecules inside or outside the pouch. The outer side of the pouch is smooth and allows good tissue integration whereas the inner wall(s) of the pouch are more open and allow cells to grow. The pouch can be used as a bioreactor for cell proliferation and/or cell differentiation. Typically, the BC pouches of the invention are not degraded in the human body and thus are well suited as cell delivery and cell containment devices. An ideal application is to use BNC as a container for transplantation of transdifferentiated cells derived from the patient's own differentiated cells, such as for example, the use of insulin-producing beta cells transdifferentiated from isolated hepatocytes as a treatment for diabetes. Since the BNC biomaterial has unique barrier properties the pouch acts also as an immunoisolation device. The pouches can thus be used for xenotransplantation of non-human cells that are used to produce a needed substance. For example, treating diabetic patients by introducing insulin-producing pig cells directly into their muscle.

"Biosynthetic nanocellulose, a natural polysaccharide, is an attractive biomaterial because of its good mechanical properties, hydroexpansivity, biocompatibility and its stability within a wide range of temperatures and pH levels. Cellulose ((.beta.-1.fwdarw.4-glucan) is the most abundant polymer of natural origin. In addition to being biosynthesized in vast amounts as structural material in the walls of plants, cellulose is also produced as an exopolysaccharide, i.e., bacterial nanocellulose (BNC), by Gluconacetobacter xylinus. Biomaterial applications require pure material and often an introduction of functional groups to stimulate the tissue regeneration process. BNC has additional advantages as a biomaterial as compared to plant-derived cellulose. Apart from good mechanical strength, high water holding capacity, high purity and accessibility to non-aggregated micro fibrils, the BNC can be molded into desirable shapes for a given application, allowing one to produce a three dimensional network of micro fibrils.

"It has been previously described that it is advantageous to cultivate bacteria inside permeable tubes. Current innovation describes cultivation of bacteria in a silicone mold in the form of pouch. Bacteria produce hydrogel-like material with smooth outer shell and porous inner wall. Such hydrogel, after removal of bacteria, form a perfect bioreactor for cell growth and cell therapy. The bacterial nanocellulose is biocompatible and integrated by tissue. It allows vascularization and is not degraded in human body. It allows small molecules to diffuse through the pouch wall while keeping cells inside.

"Particular aspects of the invention include a process to produce robust Bacterial Nanocellulose, BNC pouches with interconnected tubing with control of size, diameter, morphology, porosity and mechanical properties consisting of two steps: (a) growth of BNC hydrogel in oxygen permeable mold in the form of pouch with tubing diameter less than 5 mm by injecting into the tubing the suspension of cellulose producing bacteria in suitable medium, and (b) modifying the density of wall of the pouch by freezing and freeze drying process followed by rewetting. Processes of the invention in particular include combining a BNC hydrogel pouch with silicone tubing for cell injection.

"Such BNC hydrogel pouches produced by such methods can be seeded with cells and used for cell delivery and cell therapy.

"Other applications include where a BNC hydrogel pouch is used as a container for transplantation of transdifferentiated cells derived from the patient's own differentiated cells.

"Additional applications include using a BNC hydrogel pouch for transplantation of insulin-producing beta cells transdifferentiated from isolated hepatocytes as a treatment for diabetes. Even further, the BNC hydrogel pouches can be used for xenotransplantation of non-human cells for treating diabetic patients.

"Even further, applications for the BNC hydrogel pouches can include use of the pouches for tissue engineering, regenerative medicine and/or cancer treatment.

"In particular, embodiments of the invention include a process of preparing Bacterial Nanocellulose (BNC) pouches comprising one or more or all of (in any order): providing an oxygen permeable mold in the form of a pouch; disposing a growth medium suitable for growing BNC in the mold; disposing one end of a 5-mm or less diameter tubing in the growth medium; injecting cellulose producing bacteria through the tubing into the growth medium; and growing BNC hydrogel in the mold in a manner sufficient to form of a BNC pouch.

"Such processes can comprise modifying wall density of the pouch by any one or more of (in any combination) freezing, freeze drying, and/or rewetting the pouch.

"Such pouches can be seeded with cells.

"Processes of the invention include administering the pouch to a subject in a manner to provide for cell delivery and cell therapy to the subject.

"Embodiments further provide a BNC hydrogel pouch comprising silicone tubing disposed in the pouch in a manner to provide for injection of cells into the pouch through the tubing. Such pouches can comprise cells seeded onto the pouch.

"Processes of the invention also include a process of administering cell delivery and cell therapy to a subject comprising administering such pouches to the subject.

"A process of transplanting cells to a subject is also included which comprises disposing transdifferentiated cells derived from the subject's own differentiated cells in the pouch and administering the pouch to the subject. When referring to 'pouch' or 'method' or 'process' in the context of this invention, it is important to note that any pouch, method, or process described in this specification or figures can be used for that particular embodiment. Indeed, any pouch, method, or process or part thereof described in this specification and figures can be used in any other pouch, method, or process also described in this specification and figures in any manner.

"Even further, embodiments include a process of transplanting cells to a subject comprising disposing insulin-producing beta cells transdifferentiated from isolated hepatocytes in the pouch and administering the pouch to the subject in a manner to treat diabetes.

"Such processes of the invention include a process of xenotransplantation comprising disposing non-human cells in a pouch of the invention and administering the pouch to a diabetic patient.


"The accompanying drawings illustrate certain aspects of embodiments of the present invention, and should not be used to limit or define the invention. Together with the written description the drawings serve to explain certain principles of the invention.

"FIG. 1 is an image of a template used for production of a silicone mold used for the biofabrication production system.

"FIG. 2 is an image of the medium with bacteria in the silicone mold after 2 days of cultivation in which the BNC hydrogel has been already formed.

"FIG. 3 is an image of BNC pouches which have been removed from silicone molds and are under purification process in alkali followed by rinsing with DI water.

"FIG. 4 is an image of a purified BNC pouch with inserted silicone tubing for use in cell therapy."

URL and more information on this patent application, see: Gatenholm, Erik. Semipermeable Medical Pouches and Their Uses. Filed August 29, 2013 and posted August 14, 2014. Patent URL:

Keywords for this news article include: Tissue Engineering, Biomedical Engineering, Biomedicine, Patents, Therapy, Alcohols, Diabetes, Hydrogel, Silicones, Siloxanes, Chalcogens, Proinsulin, Hepatocytes, Endocrinology, Bioengineering, Gastroenterology, Peptide Hormones, Organic Chemicals, Polyethylene Glycols, Regenerative Medicine.

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Source: Diabetes Week

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