Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.

ADDRESSES:

Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Cell-Nanofiber Composite Based Engineered Cartilage

Description of Invention: Available for licensing and commercial development is a tissue-engineered cartilage derived from a cellular composite made from a biodegradable, biocompatible polymeric nanofibrous matrix having dispersed chondrocytes or adult mesenchymal stem cells. More particularly, tissue-engineered cartilage can be prepared where the cartilage has a biodegradable and biocompatible nanofibrous polymer matrix prepared by electrospinning and a plurality of chondocytes or mesenchymal stem cells dispersed in the pores of the matrix. The tissue-engineered cartilage possesses compressive strength properties similar to natural cartilage.

The electrospinning process is a simple, economical means to produce biomaterial matrices or scaffolds of ultra-fine fibers derived from a variety of biodegradable polymers (Li WJ, et al. J. Biomed. Mater. Res. 2002; 60:613-21). Nanofibrous scaffolds (NFSs) formed by electrospinning, by virtue of structural similarity to natural extracellular matrix (ECM), may represent promising structures for tissue engineering applications. Electrospun three-dimensional NFSs are characterized by high porosity with a wide distribution of pore diameter, high-surface area to volume ratio and morphological similarities to natural collagen fibrils (Li WJ, et al. J. Biomed. Mater. Res. 2002; 60:613-21). These physical characteristics promote favorable biological responses of seeded cells in vitro and in vivo, including enhanced cell attachment, proliferation, maintenance of the chondrocytic phenotype (Li WJ, et al. J. Biomed. Mater. Res. 2003; 67A: 1105-14), and support of chondrogenic differentiation (Li WJ, et al. Biomaterials 2005; 26:599-609) as well as other connective tissue linage differentiation (Li WJ, et al. Biomaterials 2005; 26:5158-5166). The invention based on cell-nanofiber composite represents a candidate engineered tissue for cell-based approaches to cartilage repair.

Application: Cartilage repair and methods for making tissue-engineered cartilage.

Developmental Status: Electrospinning method is fully developed and cartilage has been synthesized.

Inventors: Wan-Ju Li and Rocky Tuan (NIAMS).

Publications: The invention is further described in:

1. W-J Li et al. Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering. J Biomech. 2007;40(8):1686-1693. Epub 2006 Oct 23, doi:10.1016/jbiomech.2006.09.004.

2. W-J Li et al. Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications. Acta Biomater. 2006 Jul;2(4):377-385. Epub 2006 May 6, doi:10.1016/j.actbio.2006.02.005.

3. CK Kuo et al. Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol. 2006 Jan;18(1):64-73. Review.

4. W-J Li et al. Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials. 2005 Sep;26(25):5158-5166.

Patent Status:

U.S. Provisional Application No. 60/690,998 filed 15 Jun 2005 (HHS Reference No. E-116-2005/0-US-01).

PCT Application No. PCT/US2006/0237477 filed 15 Jun 2006 (HHS Reference No. E-116-2005/0-PCT-02).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Cell-Nanofiber Composite and Cell-Nanofiber Composite Amalgam Based Engineered Intervertebral Disc

Description of Invention: Diseased or damaged musculoskeletal tissues are often replaced by an artificial material, cadaver tissue or donated, allogenic tissue. Tissue engineering offers an attractive alternative whereby a live, natural tissue is generated from a construct made up of a patient's own cells or an acceptable/compatible cell source in combination with a biodegradable scaffold for replacement of defective tissue.

Degeneration of the intervertebral disc (IVD) is a common and significant source of morbidity in our society. Approximately 8 of 10 adults at some point in their life will experience an episode of significant low back pain, with the majority improving without any formal treatment. However, for the subject requiring surgical management current interventions focus on fusion of the involved IVD levels, which eliminates pain but does not attempt to restore disc function. Approximately 200,000 spinal fusions were performed in the United States in 2002 to treat pain associated with lumbar disc degeneration. Spinal fusion however is thought to significantly alter the biomechanics of the disc and lead to further degeneration, or adjacent segment disease. Therefore, in the past decade there has been mounting interest in the concept of IVD replacement. The replacement of the IVD holds tremendous potential as an alternative to spinal fusion for the treatment of degenerative disc disease by offering a safer alternative to current spinal fusion practices.

At the present time, several disc replacement implants are at different stages of preclinical and clinical testing. These disc replacement technologies are designed to address flexion, extension, and lateral bending motions; however, they do little to address compressive forces and their longevity is limited due to their inability to biointegrate. Therefore, a cell-based tissue engineering approach offers the most promising alternative to replace the degenerated IVD. Current treatment for injuries that penetrate subchondral bone include subchondral drilling, periosteal tissue grafting, osteochondral allografting, chondrogenic cell and transplantation; but are limited due to suboptimal integration with host tissues.

The present invention claims tissue engineered intervertebral discs comprising a nanofibrous polymer hydrogel amalgam having cells dispersed therein, methods of fabricating tissue engineered intervertebral discs by culturing a mixture of stem cells or intervertebral disc cells and a electrospun nanofibrous polymer hydrogel amalgam in a suitable bioreactor, and methods of treatment comprising implantation of tissue engineered intervertebral disc into a subject.

Application: Intervertebral disc bio-constructs and electrospinning methods for fabrication of the discs.

Developmental Status: Prototype devices have been fabricated and preclinical studies have been performed.

Inventors: Wan-Ju Li, Leon Nesti, Rocky Tuan (NIAMS).

Patent Status:

U.S. Provisional Application No. 60/847,839 filed 27 Sep 2006 (HHS Reference No. E-309-2006/0-US-01).

U.S. Provisional Application No. 60/848,284 filed 28 Sep 2006 (HHS Reference No. E-309-2006/1-US-01).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Bioreactor Device and Method and System for Fabricating Tissue

Description of Technology: Available for licensing and commercial development is a millifluidic bioreactor system for culturing, testing, and fabricating natural or engineered cells and tissues. The system consists of a millifluidic bioreactor device and methods for sample culture. Biologic samples that can be utilized include cells, scaffolds, tissue explants, and organoids. The system is microchip controlled and can be operated in closed-loop, providing controlled delivery of medium and biofactors in a sterile temperature regulated environment under tabletop or incubator use. Sample perfusion can be applied periodically or continuously, in a bidirectional or unidirectional manner, and medium re-circulated.

Advantages:

The device is small in size, and of conventional culture plate format.

Provides the ability to grow larger biologic samples than microfluidic systems, while utilizing smaller medium volumes than conventional bioreactors. The bioreactor culture chamber is adapted to contain sample volumes on a milliliter scale (10 [mu]L to 1 mL, with a preferred size of 100 [mu]L), significantly larger than chamber volumes in microfluidic systems (on the order of 1 [mu]L). Typical microfluidic systems are designed to culture cells and not larger tissue samples.

The integrated medium reservoirs and bioreactor chamber design provide for, (1) concentration of biofactors produced by the biologic sample, and (2) the use of smaller amounts of exogenous biofactor supplements in the culture medium. The local medium volume (within the vicinity of the sample) is less than twice the sample volume. The total medium volume utilized is small, preferably 2 ml, significantly smaller than conventional bioreactors (typically using 500-1000 mL).

Provides for real-time monitoring of sample growth and function in response to stimuli via an optical port and embedded sensors. The optical port provides for microscopy and spectroscopy measurements using transmitted, reflected, or emitted (e.g., fluorescent, chemiluminescent) light. The embedded sensors provide for measurement of culture fluid pressure and sample pH, oxygen tension, and temperature.

Capable of providing external stimulation to the biologic sample, including mechanical forces (e.g. fluid shear, hydrostatic pressure, matrix compression, microgravity via clinorotation), electrical fields (e.g., AC currents), and biofactors (e.g., growth factors, cytokines) while monitoring their effect in real-time via the embedded sensors, optical port, and medium sampling port.

Monitoring of biologic sample response to external stimulation can be performed non-invasively and non-destructively through the embedded sensors, optical port, and medium sampling port. Testing of tissue mechanical and electrical properties (e.g., stiffness, permeability, loss modulus via stress or creep test, electrical impedance) can be performed over time without removing the sample from the bioreactor device.

The bioreactor sample chamber can be constructed with multiple levels fed via separate perfusion circuits, facilitating the growth and production of multiphasic tissues.

Application: Cartilage repair and methods for making tissue-engineered cartilage.

Development Stage: Electrospinning method is fully developed and cartilage has been synthesized.

Inventors: Juan M. Taboas (NIAMS), Rocky S. Tuan (NIAMS), et al.

Patent Status:

U.S. Provisional Application No. 60/701,186 filed 20 Jul 2005 (HHS Reference No. E-042-2005/0-US-01).

PCT Application No. PCT/US2006/028417 filed 20 Jul 2006, which published as WO 2007/012071 on 25 Jan 2007 (HHS Reference No. E-042-2005/0-PCT-02).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.