McGowan Institute researchers investigate numerous approaches to the constructive remodeling of many different tissues. Biosynthetic and natural scaffolds are being characterized and biomechanically tested, along with additives for stimulating cell adhesion and growth, and novel ways to process materials into three-dimensional structures.
Pioneer in Extracellular Matrix
The use of extracellular matrix for the repair of soft tissues was developed by Dr. Stephen Badylak, Director of the Pre-Clinical Studies Center at the McGowan Institute and Research Professor in the Department of Surgery.
| Esophagus and trachea reconstruction As pioneers in the development of extracellular matrix scaffolds, the results of prior research has led to the utilization of ECM scaffolds in over 300,000 patients. These scaffolds have been shown to significantly promote tissue remodeling in wounds. Under the leadership of Dr. Badylak, Institute researchers are now evaluating various extracellular matrix scaffolds as agents for the reconstruction of the esophagus and trachea. In preclinical trials, a damaged section of the esophagus was replaced with a specially-formed matrix constructed from porcine urinary bladder and seeded with esophageal endothelial cells. Within 90 days, the scaffold was replaced with functional, motile tissue. |
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| The ECM technology offers innovative solutions to unique and challenging needs. As an example, Surgeons at the Children's Hospital at Montefiore Medical Center, New York City separated Carl and Clarence Aguirre, Filipino twins who were joined at the head. The doctors used Durasis Dural Substitute, a SIS-based biomaterial from Cook Biotech Inc., to replace the dura mater on the heads of the boys. This product is the outcome of the prior research of Dr. Badylak on ECM that has been licensed to Cook Biotech. Dura mater is the tough, fibrous sheath that surrounds the brain and spinal cord. The photo shows the Twins leaving Children’s Hospital [Photo Credit- The Children's Hospital at Montefiore]. |  |
| The University of Pittsburgh and Dolphin Quest-Waikoloa, Hawaii recently joined forces to apply the latest advances in human regenerative medicine in an attempt to restore a bottlenose dolphin’s damaged dorsal fin. The procedure on Liko, a three-year-old male dolphin at Dolphin Quest on Hawaii’s Big Island, took place on July 30th and marked the first-ever marine mammal application of extracellular matrix tissue repair. Liko sustained a tear at the base of his dorsal (top) fin, likely in a game of “chase” with his dolphin cohorts. A dolphin's dorsal fin consists of soft, cartilage-like tissue. |  |
| Dr. Badylak Receives Clemson Award for Applied
Research Stephen Badylak, DVM, MD, PhD is the 2005 recipient of the prestigious Clemson Award for Applied Research. The selection is based on the work of the candidate that has resulted in significant utilization or application of basic knowledge in science to accomplish a significant goal in the biomaterials area. The achievement will be evidenced by the development of a useful device or material which has achieved widespread usage or acceptance, or expanded knowledge of biomaterials/host tissue relationships which have received widespread acceptance and resulted in improvements in the clinical management of disease. |
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| Under the leadership of Dr.
Savio L-Y. Woo, Director of the Musculoskeletal Research Center,
Institute researchers are investigating the use of functional
tissue engineering approaches, including the utilization of
antisense gene therapy and bioscaffolds to enhance the healing
of ligaments following injury. Basic research is underway is
underway to elucidate how mechanical demands on healing ligaments
influence matrix synthesis, composition, porphology, organization,
and ultimately ligament function. . In addition, a robotic/UFS
testing system is utilized to determine the kinematics of the
knee and in situ forces in ligaments to assess the effects
of injury and reconstruction as well as to make recommendations
for surgical greatment and rehabilitation following knee injuries.
1. Woo, S.L-Y., Jia, F., Zou, L., and Gabriel, M.: Functional Tissue Engineering for Ligament Healing: Potential of Antisense Gene Therapy, in Annals of Biomedical Engineering, 2nd Special Edition on Musculoskeletal Bioengineering, 32(3):342-351, 2004. 2. Musahl, V., Abramowitch, S., Gilbert, T., Tsuda, E., Wang, J.H-C., and Woo, S.L-Y.: The Use of Porcine Small Intestinal Submucosa to Enhance the Healing of the Medial Collateral Ligament – A Functional Tissue Engineering Study in Rabbits. J. of Orthopaedic Research, 22:214-220, 2004. 3. Woo, S.L-Y., Fox, R.J., Sakane, M., Livesay, G.A., Rudy, T.W., and Fu, F.H.: Biomechanics of the ACL: Measurements of In Situ Force in the ACL and Knee Kinematics. Knee, 5:267-288, 1998. 4. Woo, S.L-Y., Kanamori, A., Zeminski, J., Yagi, M., Papageorgious,
C. and Fu, F.H.: The Effectiveness of Anterior Cruciate Ligament
Reconstruction by Hamstrings and Patellar Tendon: A Cadaveric
Study Comparing Anterior Tibial Load vs. Rotational Loads.
J. of Bone and Joint Surgery, 84A(6):907-914, 2002. |
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Engineered Tissue Mechanics Laboratory
| The Engineered Tissue Mechanics Laboratory under the leadership of Dr. Sacks is addressing various heart related tissue-engineered and biomaterial projects. The research includes investigations on heart valve prostheses and biomechanical properties research, development of techniques to analyze muscle derived stem cells, and the calcification of fabricated heart valves. |  |
| McGowan Institute researchers
are developing ways to guide peripheral nerve regeneration.
A new method joins FDA-approved biodegradable polymers with
porous collagen-based beads, a combination that yields enhanced
cortical neuron adhesion and viability. The guides have multiple
channels to give extending axons a larger surface area to
adhere to, enhancing their elongation. In pre-clinical studies,
a nerve guide seeded with adipose-derived stem cells restored
some hind leg mobility in rats. The focus is on the use of
adipose-derived adult stem cells for both hard and soft tissue
regeneration. The use of liposuctioned fat as a source of
autologous stem cells is both exciting and attractive. Dr.
Marra’s
laboratory is isolating, characterizing, and differentiating
adipose-derived stem cells into osteoblasts, adipocytes,
chondrocytes, and neuronal progenitor cells for tissue engineering
applications. Dr. Marra is also Co-Director of the Adipose
Stem Cell Center at the University of Pittsburgh.
Bender, M.; Bennett, J.M.; Waddell, R.; Doctor, J.S.; Marra, K.G. “Multi-Channeled Biodegradable Polymer/CultiSpher Composite Nerve Guides,” Biomaterials, 2004, 25(7-8), 1269-1278. Waddell, R.; Marra, K.G., Collins,
K.; Leung, J.; Doctor, J.S. “Biodegradable Polymer/Collagen Conduits
for Nerve Regeneration,” Biotechnology Progress, 2003,
19(6), 1767-1774. |
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Tissue Engineered Solutions for Heart Disease
| Under the leadership of Dr. William Wagner, Institute researchers have created a cardiac “patch,” a biodegradable polymer scaffold seeded with hematopoietic adult stem cells that may ultimately be used to strengthen scarred heart muscle. Preclinical testing is yielding promising results. In other projects, researchers are using extracellular matrix scaffolds, progenitor cells, and growth factors to encourage myocardial remodeling, and developing heart valves and small diameter blood vessels in collaboration with industry partners. |  |