Purdue Research FoundationNewsRx.com
By a News Reporter-Staff News Editor at Health & Medicine Week -- According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by the inventors Nauman, Eric Allen (West Lafeyette, IN); Dickerson, Darryl (West Lafayette, IN); Dunn, Jocelyn Teresia (Lafayette, IN), filed on November 16, 2012, was made available online on May 23, 2013 (see also Purdue Research Foundation).
The assignee for this patent application, patent application serial number 679248, is Purdue Research Foundation.
Reporters obtained the following quote from the background information supplied by the inventors: "Repair of soft tissue damage resulting from injury or disease presents an important medical challenge. The ability to regenerate organs in whole or part would advance treatment of diseases such as liver disease, kidney disease, and diabetes. Repair or replacement of soft tissue would also be useful in repairing or replacing heart valves, blood vessel valves, and in repairing ligaments and tendons. Reconstructive and cosmetic surgery would also be advanced by the ability to generate soft connective tissues and adipose tissue.
"Tissue engineering has long sought to develop replacement tissues for patients suffering from organ failure, often utilizing embryonic or adult stem cells as agents of tissue repair or regeneration. Unfortunately, there have been numerous demonstrations that simply injecting stem cells, even those that have been differentiated in vitro, is insufficient. Successful tissue regeneration requires the ability to promote integration with the host and to direct the tissue growth and cell differentiation, processes that depend largely on the transport characteristics of the graft as demonstrated by Hui et al. (Journal of Biomechanics 1996; 29(1):123-132).
"Three dimensional scaffolds such as collagen-based hydrogels or poly-lactic-co-glycolic acid (PLGA)-based polymer foams, have demonstrated considerable potential, but the long-term outcomes of therapies employing these scaffolds are far from satisfactory. Collagen hydrogels are contracted by resident cells as much as 90%, making it extremely difficult to promote integration with the host tissue and to generate the necessary tissue mass for organ regeneration. In addition, as hydrogels contract, they exhibit a 100-1000 fold decrease in permeability which limits their ability to transport nutrients and waste products through the implant. The primary limitation of PLGA foams is that they degrade through an autocatalytic process into acidic by-products that are technically biocompatible, but substantially lower the pH within the tissue and often lead to cyst formation. Additional challenges posed by various formulations of PLGA include low mechanical strength relative to most tissues and a surprisingly low permeability compared to structures with similar porosities.
"There remains a need in the art for compositions and methods for regenerating damaged or diseased soft tissue."
In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventors' summary information for this patent application: "In certain embodiments, the present invention provides a biocompatible scaffold made from demineralized cancellous bone that has been treated to inhibit osteoinductivity. The demineralized cancellous bone includes a region in which the collagen of the demineralized bone is stiffened. The region of demineralized bone may be stiffened by crosslinking or by physicochemically, including, but not limited to, by heating or stretching, i.e., strain hardening. The biocompatible scaffold is substantially free of mineralized bone.
"In certain embodiments the bone is cancellous or corticocancellous bone. In certain embodiments the biocompatible scaffold is machined to match, approximate, or be compatible with the shape of a soft tissue or a soft tissue defect.
"In certain embodiments, there is variation in the degree or type of crosslinking of the collagen within the crosslinked region. In certain embodiments, crosslinking is relatively low in the portion of the crosslinked region proximal to the interface between the uncrosslinked and crosslinked regions, and increases continuously or discontinuously in portions of the crosslinked region distal to the interface between the crosslinked and uncrosslinked regions.
"In certain embodiments, in the region of the biocompatible scaffold containing crosslinked demineralized bone has increased mechanical strength and/or increased resistance to degradation, e.g., enzymatic degradation, relative to the region containing uncrosslinked demineralized bone. In certain embodiments the at least one region comprising crosslinked demineralized bone does not exhibit cell attachment that is substantially different relative to the cell attachment to the at least one region comprising contiguous uncrosslinked demineralized bone. In certain embodiments the at least one region comprising crosslinked demineralized bone exhibits altered cell attachment, e.g. increased or decreased, relative to the cell attachment to the at least one region comprising contiguous uncrosslinked demineralized bone.
"In certain embodiments of the above described biocompatible scaffold, at least some portion of the scaffold, including at least some of the pores, contain a hydrogel. In certain further embodiments the hydrogel contains biomolecules. In certain other embodiments of the above described biocompatible scaffold, least some portion of the scaffold, including at least some of the pores, contain a polymer. In certain further embodiments the polymer comprises biomolecules. In certain other embodiments of the above described biocompatible scaffold, the scaffold comprises surface chemistry that includes covalently attached biomolecules and/or adsorbed biomolecules. In certain other embodiments of the above described biocompatible scaffold, the scaffold comprises a surface that has acquired texture, roughness, or three-dimensional unevenness by chemical etching and/or physical etching and/or laser etching. In certain other embodiments of the above described biocompatible scaffold, some or all regions are encapsulated by a biocompatible layer. In certain further embodiments the biocompatible layer is semipermeable and/or bioresorbable.
"Turning to another embodiment, there is provided a method for repairing or regenerating soft tissue comprising implanting in the soft tissue in need of repair or regeneration, any of the herein described biocompatible scaffolds. In certain embodiments, the soft tissue comprises organ tissue, e.g., liver tissue.
"It is an advantage that a bioscaffold according to the present invention can be designed to have features and performance characteristics suitable for the particular application(s) in which the bioscaffold will be used, including, for example, permeability needed for fluid transport, strength, flexibility, cell attachment, shape retention, porosity, connectivity, and the like.
"These and other aspects and embodiments of the herein described invention will be evident upon reference to the following detailed description and attached drawings. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference in their entirety, as if each was incorporated individually. Aspects and embodiments of the invention can be modified, if necessary, to employ concepts of the various patents, applications and publications to provide yet further embodiments.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
"FIG. 1 shows MicroCT images of vertebral (top), pelvic (middle) and femoral (bottom) porcine cancellous bone.
"FIG. 2 shows compressive stress-strain curves for demineralized cancellous bone.
"FIG. 3 is a plot of compressive tissue modulus as a function of volume fraction for various demineralized cancellous bone.
"FIG. 4 is a plot of porosity as a function of permeability.
"FIG. 5 shows compressive stress-strain curves for crosslinked and uncrosslinked samples.
"FIG. 6 is an image of a scaffold with Hoechst stained, rat fibroblast cells attached."
For more information, see this patent application: Nauman, Eric Allen; Dickerson, Darryl; Dunn, Jocelyn Teresia. Compositions and Methods for Repair Or Regeneration of Soft Tissue. U.S. Patent Application Serial Number 679248, filed November 16, 2012, and posted May 23, 2013. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=1344&p=27&f=G&l=50&d=PG01&S1=20130516.PD.&OS=PD/20130516&RS=PD/20130516
Keywords for this news article include: Tissue Engineering, Biomedical Engineering, Biomedicine, Patents, Legal Issues, Bone Research, Bioengineering, Purdue Research Foundation, Extracellular Matrix Proteins.
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