badylak-patents

![](0logo.gif)  
**[rexresearch.com](../index.htm)**

---

**Stephen BADYLAK**

**Regeneration Grafts**



---

**<http://www.mirm.pitt.edu/people/bios/Badylak1.asp>**

Stephen Francis Badylak, D.V.M., Ph.D., M.D.   
Affiliation:  University of Pittsburgh   
Title:  Research Professor, Department of Surgery   
Director of Tissue Engineering, McGowan Institute for
Regenerative Medicine   
Lab Contact Info:   
Stephen F. Badylak, DVM, MD, PhD   
McGowan Institute for Regenerative Medicine   
100 Technology Drive, Suite 200   
Pittsburgh, PA 15219   
Phone: (412) 235-5145   
Fax: (412) 235-5110   
badylaks@upmc.edu   
www.mirm.pitt.edu

---

[**http://www.dailymail.co.uk/pages/live/articles/technology/technology.html?in\_article\_id=563099&in\_page\_id=1965&ct=5**](http://www.dailymail.co.uk/pages/live/articles/technology/technology.html?in_article_id=563099&in_page_id=1965&ct=5)

**foxnews.com** ( Thursday, May 01, 2008 )   
http://www.foxnews.com/story/0,2933,353636,00.html

  

# 'Pixie Dust' From Pig's Bladder Regrows Man's Finger

  

***With the help of an experimental powder, a mans severed
finger has regrown to its original length in just four
weeks, reports Londons Daily Mail.***

\* ![](badylak1.jpg)\*

**[ Stephen Badylak**, a senior research scientist at
Purdue University, holds a piece of material harvested from
a pig's bladder. ]

Lee Spievack, of Cincinnati, who sliced almost half an inch
off the top of one of his fingers, described the powder as
pixie dust, according to the newspaper.

The pixie dust is actually extra-cellular matrix, bursting
with collagen and is made from a dried pigs bladder, the
newspaper reports.

The dust was designed to regenerate damaged ligaments in
horses, the Daily Mail said.

Collagen is known to give skin strength and elasticity. It is
thought that the dust kick-starts the body's natural healing
process by sending out signals that mobilize the body's own
cells into repairing the damaged tissue, according to the
newspaper.

Spievack said his finger even has a fingernail and
fingerprint.

Spievack injured his finger three years ago when it got
caught in the propeller of a model plane. He did not want a
skin graft, opting instead to try the pixie dust.

There are all sorts of signals in the body, said Dr.
Stephen Badylak of the McGowan Institute for Regenerative
Medicine at the University of Pittsburgh. We have signals
that are good for forming scar tissue and others that are good
for regenerating tissues.

"One way to think about these matrices is that we've taken
out many of the stimuli for scar tissue formation and left
those signals which were always there for constructive
remodeling."

Essentially, the powder directs tissues to grow fresh instead
of forming a scar.

Spievak has not lost any bone, nerves or tendon material.

---

**Video : <http://news.bbc.co.uk/2/hi/health/7354458.stm>**  
**BBC NEWS: <http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/7354458.stm>
(2008/04/30 )**

  

**The Man Who Grew a Finger**

**By Matthew Price**   
**BBC News, Ohio**

  

In every town in every part of this sprawling country you can
find a faceless sprawling strip mall in which to do the
shopping.

Rarely though would you expect to find a medical miracle
working behind the counter of the mall's hobby shop.

That however is what Lee Spievak considers himself to be.

"I put my finger in," Mr Spievak says, pointing towards the
propeller of a model aeroplane, "and that's when I sliced my
finger off."

It took the end right off, down to the bone, about half an
inch.

"We don't know where the piece went."

The photos of his severed finger tip are pretty graphic. You
can understand why doctors said he'd lost it for good.

Today though, you wouldn't know it. Mr Spievak, who is 69
years old, shows off his finger, and it's all there, tissue,
nerves, nail, skin, even his finger print.

**'Pixie dust'**

How? Well that's the truly remarkable part. It wasn't a
transplant. Mr Spievak re-grew his finger tip. He used a
powder - or pixie dust as he sometimes refers to it while
telling his story.

Mr Speivak's brother Alan - who was working in the field of
regenerative medicine - sent him the powder.

For ten days Mr Spievak put a little on his finger.

"The second time I put it on I already could see growth. Each
day it was up further. Finally it closed up and was a finger.

"It took about four weeks before it was sealed."

Now he says he has "complete feeling, complete movement."

The "pixie dust" comes from the University of Pittsburgh,
though in the lab Dr Stephen Badylak prefers to call it extra
cellular matrix.

**Pig's bladder**

The process he has been pioneering over the last few years
involves scraping the cells from the lining of a pig's
bladder.

Please turn on JavaScript. Media requires JavaScript to play.

How it works in detail The remaining tissue is then placed
into acid, "cleaned" of all cells, and dried out.

It can be turned into sheets, or a powder.

It looks like a simple process, but of course the science is
complex.

"There are all sorts of signals in the body," explains Dr
Badylak.

"We have got signals that are good for forming scar, and
others that are good for regenerating tissues.

"One way to think about these matrices is that we have taken
out many of the stimuli for scar tissue formation and left
those signals that were always there anyway for constructive
remodelling."

In other words when the extra cellular matrix is put on a
wound, scientists believe it stimulates cells in the tissue to
grow rather than scar.

If they can perfect the technique, it might mean one day they
could repair not just a severed finger, but severely burnt
skin, or even damaged organs.

**Clinical trial**

They hope soon to start a clinical trial in Buenos Aires on a
woman who has cancer of the oesophagus.

The normal procedure in such cases is often deadly. Doctors
remove the cancerous portion and try to stretch the stomach
lining up to meet the shortened oesophagus.

In the trial they will place the extra cellular matrix inside
the body from where the portion of oesophagus has been
removed, and hope to stimulate the cells around it to re-grow
the missing portion.

So could limbs be re-grown? Dr Badylak is cautious, but
believes the technology is potentially revolutionary.

"I think that within ten years that we will have strategies
that will re-grow the bones, and promote the growth of
functional tissue around those bones. And that is a major step
towards eventually doing the entire limb."

That kind of talk has got the US military interested.

They are just about to start trials to re-grow parts of the
fingers of injured soldiers.

**Skin burns**

They also hope the matrix might help veterans like Robert
Henline re-grow burnt skin.

He was almost killed in an explosion while serving in Iraq.
His four colleagues travelling with him in the army Humvee
were all killed.

He suffered 35% burns to his head and upper body. His ears
are almost totally gone, the skin on his head has been burnt
to the bone, his face is a swollen raw mess.

So far he has undergone surgery 25 times. He reckons he has
got another 30 to go.

Anything that could be done in terms of regeneration would be
great he says.

"Life changing! I think I'm more scared of hospitals than I
am of going back to Iraq again."

Like any developing technology there are many unknowns. There
are worries about encouraging cancerous growths by using the
matrix.

Doctors though believe that within the so called pixie dust
lies an amazing medical discovery.

---

[**http://www.esquire.com/features/esquire-100/pigfinger1007**](http://www.esquire.com/features/esquire-100/pigfinger1007)  
[**http://www.esquire.com/features/esquire-100/pigfinger1007-2**](http://www.esquire.com/features/esquire-100/pigfinger1007-2)

---

   

**Badylak's Patents**

  

**Vascularization Enhanced Graft Constructs**   
**NZ536563**

*Abstract* --- A tissue graft construct for use in
repairing diseased or damaged tissues is provided. The tissue
graft construct comprises a tissue material comprising
submucosa selected from the group consisting of urinary
bladder submucosa and stomach submucosa, and extracts and
hydrolysates thereof, added endothelial cells, and at least
one additional preselected, exogenous population of cells, and
wherein the tissue graft construct is seeded in vitro with the
added cells. The preselected population of cells can be a
population of non-keratinized or keratinized epithelial cells
or a population of mesodermally-derived cells selected from
the group consisting of fibroblasts, smooth muscle cells,
skeletal muscle cells, cardiac muscle cells, multi-potential
progenitor cells, pericytes, osteogenic cells, and any other
suitable cell type, preferably selected based on the tissue to
be repaired. Methods for enhancing the vascularization in vivo
of these tissue graft constructs and for preparing these graft
constructs are also provided.

  
**WOUND HEALING POLYMERIC NETWORKS**  **CA2613540**

*Abstract*  --- A composition includes at least one
biologically active agent covalently attached to a first
polymerizing molecule that is adapted to undergo a free
radical polymerization. The first polymerizing molecule
retains the ability to undergo free radical polymerization
after attachment of the bioactive agent thereto. The first
polymerizing molecule is preferably biocompatible. The
polymerizing molecule can, for example, be
dihydroxyphenyl-L-alanine (DOPA) or tyrosine. The composition
can also include a second component synthesized by reacting at
least one core molecule having a plurality of reactive
hydrogen groups with at least one multi-isocyanate functional
molecule to create a conjugate including terminal isocyanate
groups. The conjugate molecule is reacted with a second
polymerizing molecule that is adapted to undergo a fre e
radical polymerization. The second polymerizing molecule
includes a reactive hydrogen to react with the isocyanate
groups of the conjugate. The second polymerizing molecule
retains the ability to undergo the free radical polymerization
after reaction with the conjugate. In several embodiments, th
e first polymerizing molecule and the second polymerizing
molecule are the sam e and dihydroxyphenyl-L-alanine (DOPA) or
tyrosine.

 **Decellularized Liver for Repair of Tissue and Treatment of
Organ Deficiency**  **US2008058956**

*Abstract* --- The present invention provides a
liver-derived devitalized mammalian parenchymatous tissue
composition which includes an interstitial structure of
connective tissue which can serve as a scaffold for tissue
repair or regeneration. The devitalized mammalian
parenchymatous tissue composition can further include the
basement membrane of the tissue.

**BIOHYBRID ELASTOMERIC SCAFFOLDS AND METHODS OF USE**  **WO2008008266**

*Abstract* --- Provided herein is a biohybrid
elastomeric scaffold comprising a synthetic polymeric
component and a biological polymeric component. The scaffold
can be fabricated to have many different forms, non-limiting
examples of which include a non-woven fibrous mesh or in a
porous composite. Methods of use of the biohybrid elastomeric
scaffolds in wound healing and tissue regeneration are also
provided.

  
**PERFORATED SUBMUCOSAL TISSUE GRAFT CONSTRUCTS**  **JP2007289734**

*Abstract* --- PROBLEM TO BE SOLVED: To provide a
perforated unitary multi-laminar tissue graft construct and a
method for preparing such construct.   
SOLUTION: This method includes: a step of overlapping strips
of submucosa tissue with other strips of submucosal tissue; a
step of compressing at least the overlapped portions of the
strips between two surfaces under conditions that allow or
promote dehydration of the compressed submucosa sheets; and a
step of perforating the resulting unitary tissue graft
construct. The perforated tissue graft compositions have
enhanced mechanical and remodeling properties relative to
non-perforated submucosal tissue grafts.

  
**ARTIFICIAL VASCULAR VALVES**  **JP2007222662**

*Abstract* --- PROBLEM TO BE SOLVED: To prepare tissue
valve formations from submucosal tissue and to provide a
method and an artificial tissue valve for replacing or fixing
damaged or diseased heart and vascular valves of a
warm-blooded vertebrate using these valve formations.   
SOLUTION: One method shows that sheets of submucosal tissue
are shaped into a tubular structure by spirally wrapping the
sheet of submucosal tissue 2 around a cylindrical mandrel 12
of the appropriate diameter and by compressing the overlapped
tissue under dehydrating conditions. The mandrel 12 is a
hollow cylinder made of plastic or metal having a plurality of
holes 16 formed in the cylinder wall. The compression of the
tissue can be achieved by forming a seal at one end of the
mandrel 12 and pulling a vacuum through the lumen of the
mandrel 12. The final seam of the spirally wrapped tissue can
be further secured by sutures, spot-welding with heat or
treating the seam with glutaraldehyde.

  
**Composition and Method for Production of Transformed Cells**
 **US2007202599**

*Abstract* --- A composition useful for the production
of transformed eukaryotic cells is described. The composition
comprises submucosal tissue and a nucleic acid sequence. The
nucleic acid sequence is typically recombinant DNA including
gene(s) encoding for one or more biofunctional proteins. The
submucosal tissue component of the present composition
comprises the tunica submucosa of vertebrate intestine
delaminated from the tunica muscularis and at least the
luminal portion of the tunica mucosa. Injection or
implantation of the composition into a host induces the
formation of transformed cells capable of expressing gene(s)
encoded by the nucleic acid sequence.

  
**EXTRACELLULAR MATRIX BASED GASTROESOPHAGEAL JUNCTION
REINFORCEMENT DEVICE**  **WO2007084278**

*Abstract* --- Provided are medical devices for
implantation in patients having suffered the loss of or damage
to at least part of their esophagus. The medical device
connects the esophagus or remaining part thereof with the
stomach to form a gastro-esophageal junction that promotes
healing and encourages new host tissue growth while
distributing the load arid decreasing tension at the
anastomotic site. The medical device comprises extracellular
matrix shaped into a conformation that more closely
approximates the geometry of the native gastro-esophageal
junction than does direct attachment of the stomach to the
shortened esophagus. Molds useful in manufacturing the medical
device and methods of use of the device are also described
herein.

 **Extracellular Matrix Based Gastroesophageal Junction
Reinforcement Device**  **US2007166396**

*Abstract* --- Provided are medical devices for
implantation in patients having suffered the loss of or damage
to at least part of their esophagus. The medical device
connects the esophagus or remaining part thereof with the
stomach to form a gastro-esophageal junction that promotes
healing and encourages new host tissue growth while
distributing the load and decreasing tension at the
anastomotic site. The medical device comprises extracellular
matrix shaped into a conformation that more closely
approximates the geometry of the native gastro-esophageal
junction than does direct attachment of the stomach to the
shortened esophagus. Molds useful in manufacturing the medical
device and methods of use of the device are also described
herein.

**Enhanced Submucosal Tissue Graft Constructs**  **US6087157**

*Abstract* --- An improved tissue graft construct
comprising submucosa of a warm-blooded vertebrate and a
preselected group of eukaryotic cells are described. The
improved tissue graft constructs can be used in accordance
with the present invention to enhance the repair of damaged or
diseased tissues in vivo.

 **SUBMUCOSA AS GROWTH SUBSTRATE FOR CELL**  **JP2007105031**

*Abstract* --- PROBLEM TO BE SOLVED: To provide a cell
culture method which promotes proliferation and tissue
differentiation of eukaryotic cells in vitro.   
SOLUTION: Cell growth of cell/tissue culture is improved by
using submucosal tissue of warm-blooded vertebrate as the
substrate of in vitro cell/tissue proliferation. A collagen
substrate environment similar to an environment found in vivo
is provided to cells in vitro by a submucosal tissue cell
growth substrate. The submucosal tissue promotes proliferation
and differentiation of eukaryotic cells when the cells are
brought into contact with submucosal tissue under conditions
inducive to cell proliferation.

**BIOMATERIAL DERIVED FROM VERTEBRATE LIVER TISSUE**  **ES2263185T**

*Abstract* ---  A tissue graft composition
comprising liver basement membrane is described. The graft
composition can be implanted to replace or induce the repair
of damaged or diseased tissues.

 **Wound healing polymeric networks**  **US2007014755**

*Abstract* --- A composition includes at least one
biologically active agent covalently attached to a first
polymerizing molecule that is adapted to undergo a free
radical polymerization. The first polymerizing molecule
retains the ability to undergo free radical polymerization
after attachment of the bioactive agent thereto. The first
polymerizing molecule is preferably biocompatible. The
polymerizing molecule can, for example. be
dihydroxyphenyl-L-alanine (DOPA) or tyrosine. The composition
can also include a second component synthesized by reacting at
least one core molecule having a plurality of reactive
hydrogen groups with at least one multi-isocyanate functional
molecule to create a conjugate including terminal isocyanate
groups. The conjugate molecule is reacted with a second
polymerizing molecule that is adapted to undergo a free
radical polymerization. The second polymerizing molecule
includes a reactive hydrogen to react with the isocyanate
groups of the conjugate. The second polymerizing molecule
retains the ability to undergo the free radical polymerization
after reaction with the conjugate. In several embodiments, the
first polymerizing molecule and the second polymerizing
molecule are the same and dihydroxyphenyl-L-alanine (DOPA) or
tyrosine.

 **Stent with reduced thrombogenicity**  **EP1704835**  
  

*Abstract* --- A tissue graft construct and method
for repairing the inner linings of damaged or diseased
vertebrate vessels are described. The method comprises the
steps of positioning a tissue graft construct within a blood
vessel at a site in need of repair. The tissue graft construct
comprises a stent (3) covered with submucosal tissue (4)
wherein the stent (3) is formed for receiving the distal end
of a catheter (1) having an inflatable balloon (2).

  
 **STOMACH SUBMUCOSA DERIVED TISSUE GRAFT**  **DE69734218T**

*Abstract* --- A tissue graft composition comprising
stomach submucosal tissue delaminated from both the luminal
portion of the tunica mucosa and the smooth muscle layers of
the muscularis externa of a stomach of a warm blooded
vertebrate is described. The graft composition can be or
implanted into a host to replace or support damaged or
diseased tissues.

  
**Artificial vascular valves**  **EP1671604**

*Abstract* --- A method for preparing vascular valves
from submucosal tissue is described. The artificial vascular
valves of the present invention are useful for replacing
damaged or diseased valves of a warm-blooded vertebrae.

  
**Large area submucosal tissue graft constructs**  **DK0821590T**

*Abstract* --- A unitary heterolaminar tissue graft
construct is prepared by fusing partially overlapped strips or
sheets of submucosa tissue. The submucosa components are fused
by compressing at least the overlapped positions of said
strips between two surfaces under conditions that allow or
promote dehydration of the compressed submucosa sheets. Three
dimensional graft constructs can be prepared by using
complementary non-planar compressive surfaces.

 **Vascularization enhanced intestinal submucosa tissue graft
constructs**   
**NZ536611**  
  

*Abstract* --- An intestinal submucosa tissue graft
construct for use in repairing diseased or damaged tissues in
non-human animals is provided. The graft construct comprises
vertebrate intestinal submucosa tissue, added endothelial
cells, and at least one additional preselected, exogenous
population of cells, which enhances initiation of the
formation of vessel-like structures in the graft. The
preselected population of cells can be a population of
non-keratinized or keratinized epithelial cells or a
population of mesodermally derived cells selected from the
group consisting of fibroblasts, smooth muscle cells, skeletal
muscle cells, cardiac muscle cells, multi-potential progenitor
cells, pericytes, osteogenic cells, and any other suitable
cell type, preferably selected based on the tissue to be
repaired. Methods for enhancing the vascularization in vivo of
these intestinal submucosa tissues graft constructs and for
preparing these grafts constructs are also provided.

**CONDITIONED MATRIX COMPOSITIONS FOR TISSUE RESTORATION**  **EP1644011**

*Abstract* --- The invention provides a composition
conditioned for the remodeling, restoration, repair, or
replacement of tissue within a host. The composition is
conditioned by culturing cells on the matrix and/or by
exposing the cultured cells or matrix to one or more
stressors.

  
**BLADDER RECONSTRUCTION METHOD AND TISSUE GRAFT FOR**  **JP2005349213**  
  

*Abstract* --- PROBLEM TO BE SOLVED: To provide a
method of replacing a surgically removed bladder defect part
in order to promote regrowth of endogenous urinary bladder
tissue.

SOLUTION: The damaged bladder tissue is surgically replaced
with a tissue graft structure made of submucosal tissue of a
warm blooded vertebrate formed in the bladder-like shape. The
submucosal tissue includes a lumen part of the mucosa layer
and a mucosal lower layer separated from a muscular coat.

  
**SCAFFOLD FOR CELL GROWTH AND DIFFERENTIATION** **US2004175366**  
  

*Abstract* --- The present invention provides a
devitalized mammalian parenchymatous tissue composition which
includes an interstitial structure which can serve as a
scaffold for tissue repair or regeneration. The devitalized
mammalian parenchymatous tissue composition can further
include the basement membrane of the tissue.

 **BONE TRANSPLANTATION COMPOSITION**  **JP2005161062**  
  

*Abstract* --- PROBLEM TO BE SOLVED: To provide a
restoring guidance method for a damaged bone or a diseased
bone. SOLUTION: In order to restore and guide the damaged bone
or the diseased bone, a process to transplant the effective
dose of a powdery biodegradable bone transplantation
composition to a damaged or diseased sector is provided. The
above-mentioned bone transplantation composition comprises a
submucosa exfoliated from a luminal part of the intestines
section of a vertebrate, or its digests. It is a powdery
material which is compressed into a given three-dimensional
shape before a transplantation. It is transplanted to the
damaged bone or the diseased bone.

**Tubular submucosal graft constructs**   
**AU2004216679**

**Biomaterial derived from vertebrate liver tissue**   
**US2005019419**

*Abstract* --- A tissue graft composition comprising
liver basement membrane and a method of preparation of this
tissue graft composition are described. The graft composition
can be implanted to replace or induce the repair of damaged or
diseased tissues.

**Conditioned compositions for tissue restoration**   
**US2005025838**

*Abstract* --- The invention provides a composition
conditioned for the remodeling, restoration, repair, or
replacement of tissue within a host. The composition is
conditioned by culturing cells on the matrix and/or by
exposing the cultured cells or matrix to one or more
stressors.

**Gastric submucosal tissue as a novel diagnostic tool**   
**US2004157283**

*Abstract* ---  A cell culture growth substrate
comprising submucosal tissue of a warm-blooded vertebrate and
a method for culturing fastidious organisms is described.
Submucosal tissue used in accordance with the present
invention supports the proliferation of cells when said cells
are contacted with submucosal tissue under conditions
conducive to cell proliferation.

**Biomaterial derived from vertebrate liver tissue**   
**US2004157323**

*Abstract* --- A tissue graft composition comprising
liver basement membrane is described. The graft composition
can be implanted to replace or induce the repair of damaged or
diseased tissues.

**Method for repair of liver tissue**   
**US2004187877**

*Abstract* --- A method for inducing the repair of
damaged or diseased liver tissue in vivo is provided. The
method comprises the step of administering to the patient a
graft composition comprising basement membrane tissue of a
warm-blooded vertebrate in an amount effective to induce the
repair of the liver tissue at the site of administration of
the graft composition.

**Method for repair of body wall**   
**US2004191226**

*Abstract* --- A method for inducing the repair of
damaged or diseased body wall tissues is provided. In one
embodiment, damaged or diseased body wall tissue is replaced
with basement membranes of a warm-blooded vertebrate to
promote regrowth of body wall tissues to form a multilaminate
structure.

**Composition and method for production of transformed cells**
  
**US2005003537**

*Abstract* ---A composition useful for the production of
transformed eukaryotic cells is described. The composition
comprises submucosal tissue and a nucleic acid sequence. The
nucleic acid sequence is typically recombinant DNA including
gene(s) encoding for one or more biofunctional proteins. The
submucosal tissue component of the present composition
comprises the tunica submucosa of vertebrate intestine
delaminated from the tunica muscularis and at least the
luminal portion of the tunica mucosa. Injection or
implantation of the composition into a host induces the
formation of transformed cells capable of expressing gene(s)
encoded by the nucleic acid sequence.

**Vascularization enhanced graft constructs**   
**US2004006395**

*Abstract* --- A tissue graft construct for use in
repairing diseased or damaged tissues is provided. The tissue
graft construct comprises a matrix composition selected from
the group consisting of urinary bladder submucosa and stomach
submucosa, and extracts and hydrolysates thereof, added
endothelial cells, and at least one additional preselected,
exogenous population of cells which enhance initiation of the
formation vessel-like structures in the graft construct. The
preselected population of cells can be a population of
non-keratinized or keratinized epithelial cells or a
population of mesodermally-derived cells selected from the
group consisting of fibroblasts, smooth muscle cells, skeletal
muscle cells, cardiac muscle cells, multi-potential progenitor
cells, pericytes, osteogenic cells, and any other suitable
cell type, preferably selected based on the tissue to be
repaired. Methods for enhancing the vascularization in vivo of
these tissue graft constructs and for preparing these graft
constructs are also provided.

**Vascularization enhanced graft constructs**   
**US2003216812**

*Abstract* --- A tissue graft construct for use in
repairing diseased or damaged tissues is provided. The tissue
graft construct comprises a matrix composition selected from
the group consisting of liver basement membrane and extracts
and hydrolysates thereof, and processed collagen from
vertebrate non-submucosal sources, added endothelial cells,
and at least one additional preselected, exogenous population
of cells which enhance the initiation of vessel-like
structures in the grant. The preselected population of cells
can be a population of non-keratinized or keratinized
epithelial cells or a population of mesodermally derived cells
selected from the group consisting of fibroblasts, smooth
muscle cells, skeletal muscle cells, cardiac muscle cells,
multi-potential progenitor cells, pericytes, osteogenic cells,
and any other suitable cell type, preferably selected based on
the tissue to be repaired. Methods for enhancing the
vascularization in vivo of these tissue graft constructs and
for preparing these graft constructs are also provided.

**Vascularization enhanced graft constructs**   
**US2003216811**

*Abstract* --- An intestinal submucosa tissue graft
construct for use in repairing diseased or damaged tissues is
provided. The graft construct comprises vertebrate intestinal
submucosa tissue, added endothelial cells, and at least one
additional preselected, exogenous population of cells which
enhances initiation of the formation of vessel-like structures
in the graft. The preselected population of cells can be a
population of non-keratinized or keratinized epithelial cells
or a population of mesodermally derived cells selected from
the group consisting of fibroblasts, smooth muscle cells,
skeletal muscle cells, cardiac muscle cells, multi-potential
progenitor cells, pericytes, osteogenic cells, and any other
suitable cell type, preferably selected based on the tissue to
be repaired. Methods for enhancing the vascularization in vivo
of these intestinal submucosa tissue graft constructs and for
preparing these graft constructs are also provided.

**VASCULARIZATION ENHANCED GRAFT CONSTRUCTS**   
**WO03092604**

*Abstract* --- A tissue graft construct for use in
repairing diseased or damaged tissues is provided. The tissue
graft construct comprises a matrix composition selected from
the group consisting of liver basement membrane and extracts
and hydrolysates thereof, and processed collagen from
vertebrate non-submucosal sources, added endothelial cells,
and at least one additional preselected, exogenous population
of cells which enhance the initiation of vessel-like
structures in the grant.. The preselected population of cells
can be a population of non-keratinized or keratinized
epithelial cells or a population of mesodermally derived cells
selected from the group consisting of fibroblasts, smooth
muscle cells, skeletal muscle cells, cardiac muscle cells,
multi-potential progenitor cells, pericytes, osteogenic cells,
and any other suitable cell type, preferably selected based on
the tissue to be repaired. Methods for enhancing the
vascularization in vivo of these tissue graft constructs and
for preparing these graft constructs are also provided.

**COMPOSITION AND METHOD FOR INHIBITING HYPERSENSITIVITY**
  
**WO03059284**

*Abstract* --- The present invention is directed to
methods, compositions, and devices for preventing or
inhibiting undesired sensitization reactions of the skin or
mucosa caused by a component of a transdermal or transmucosal
drug delivery system. A method is provided wherein a matrix
composition is administered to intact skin or mucosa of a
vertebrate in combination with a transdermal or transmucosal
drug delivery system to inhibit sensitization of the skin or
mucosa by a component of the delivery system. The invention is
also directed to a pharmaceutical composition comprising the
transdermal or transmucosal drug delivery system, a
therapeutically effective amount of a drug, and a
therapeutically effective amount of a sensitization inhibitory
composition comprising a matrix composition, and to a delivery
device for administration of such a composition.

**COMPOSITION AND METHOD FOR INHIBITING HYPERSENSITIVITY**
  
**WO03059221**

*Abstract* --- The present invention is directed to
methods, compositions, and devices for preventing or
inhibiting undesired sensitization reactions of the skin or
mucosa caused by a component of a transdermal or transmucosal
drug delivery system. A method is provided wherein an
intestinal submucosa composition is administered to intact
skin or mucosa of a vertebrate in combination with a
transdermal or transmucosal drug delivery system to inhibit
sensitization of the skin or mucosa by a component of the
delivery system. The invention is also directed to a
pharmaceutical composition comprising the transdermal or
transmucosal drug delivery system, a therapeutically effective
amount of a drug, and a therapeutically effective amount of a
sensitization inhibitory composition comprising an intestinal
submucosa composition, and to a device for administering such
a composition.

**BIOMATERIAL DERIVED FROM VERTEBRATE LIVER TISSUE**   
**WO03059061**

*Abstract* --- A tissue graft composition comprising
liver basement membrane and a method of preparation of this
tissue graft composition are described. The graft composition
can be implanted to replace or induce the repair of damaged or
diseased tissues.

**Reduction of stent thrombogenicity**   
**US2003065379**

*Abstract* --- A tissue graft construct and method for
repairing the inner linings of damaged or diseased vertebrate
vessels is described. The method comprises the steps of
positioning a tissue graft construct within a blood vessel at
a site in need of repair. The tissue graft construct comprises
a stent (3) covered with submucosal tissue (4) wherein the
stent (3) is formed for receiving the distal end of a catheter
(1) having an inflatable balloon (2).

**Enhanced submucosal tissue graft constructs**   
**US7175841**

Abstract --- An improved tissue graft construct comprising
submucosa of a warm-blooded vertebrate and a preselected group
of eukaryotic cells are described. The improved tissue graft
constructs can be used in accordance with the present
invention to enhance the repair of damaged or diseased tissues
in vivo.

**Tissue regenerative composition**  **US2004043006**  
  
*Abstract* --- A matrix, including epithelial basement
membrane, for inducing repair of mammalian tissue defects and in
vitro cell propagation derived from epithelial tissues of a
warm-blooded vertebrate.

---

**Biomaterial derived from vertebrate liver tissue**  **US6793939**

*Abstract* --- A tissue graft composition comprising liver
basement membrane is described. The graft composition can be
implanted to replace or induce the repair of damaged or diseased
tissues.

**Purified submucosa graft material**   
**US2004078076**

*Abstract* --- A graft prostheses (11), materials and
method for implanting, transplanting, replacing, or repairing
a part of a patient. The graft prosthesis includes a purified,
collagen-based matrix structure delaminaetd from a submucosa
tissue source. The submucosa tissue source is purified to
remove contaminants, thereby making the purified and
delaminated structure biocompatible and suitable for grafting
on and/or in a patient.

**Gastric submucosal tissue as a novel diagnostic tool**   
 **US6696270**

*Abstract* --- A cell culture growth substrate
comprising submucosal tissue of a warm-blooded vertebrate and
a method for culturing fastidious organisms is described.
Submucosal tissue used in accordance with the present
invention supports the proliferation of cells when said cells
are contacted with submucosal tissue under conditions
conducive to cell proliferation.

  
**Method for vocal cord reconstruction**  **US6918396**  
  

*Abstract* --- A method for surgical repair of
damaged or diseased head and neck tissues is described. In one
aspect of the invention tissue graft constructs comprising
vertebrate submucosa or vertebrate basement membrane materials
are used to repair and promote growth of endogenous vocal cord
tissue.

---

**Artificial vascular valves**   
**AU5181101**

**Tubular submucosal graft constructs**   
**AU2816101**

  


---

---