[Federal Register Volume 72, Number 207 (Friday, October 26, 2007)]
[Notices]
[Pages 60863-60865]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-21100]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

[[Page 60864]]


ACTION: Notice.

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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; 
[email protected].

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.

[[Page 60865]]

    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; 
[email protected].

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; 
[email protected].

    Dated: October 22, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-21100 Filed 10-25-07; 8:45 am]
BILLING CODE 4140-01-P