McGowan Institute?
February 2005 | VOL. 2 | www.McGowan.pitt.edu
To investigate the complex process of inflammation and its relationship to regenerative medicine, the McGowan Institute established the Center for Inflammation and Regeneration Modeling (CIRM).
The human body has an inherent ability to repair many of its own organs and tissues following damage from either disease or trauma. One goal of medicine has been to facilitate this intrinsic self-renewing ability by relieving damaged tissues of their functional burden and providing what was empirically perceived to be the ideal environment for tissue healing.
During the last century, newer concepts emerged, including replacement of diseased tissues with synthetic materials — such as heart valves and artificial joints — and, more recently, transplanted organs and engineered tissues. In many cases, the patient has suffered such significant and irreparable tissue damage that the only option to restore function is an implant or organ transplant.
We believe that a large number of patients with organ failure would be better served by modalities of treatment that embrace the historic principle of medicine: optimizing the regenerative potential intrinsic to many organ systems. Through CIRM we study regenerative medicine to understand how we can facilitate the body’s ability to heal itself.
Why study inflammation?
To achieve this goal, we must understand and acknowledge the pivotal role of inflammation — first, in the initial damage process and then, in the various aspects of the healing response and tissue remodeling following injury.
Inflammation can be described as a process initiated by various insults to the organism and resulting in organ damage or dysfunction. Therapeutic approaches involving temporary organ support, which are designed to allow the injured organ to regain function, often themselves cause additional inflammation because of the technique or device used or the invasive procedure necessary to implement the therapy.
Despite enormous progress in studying the human immune system, a holistic understanding of the immune/inflammatory response is not yet in grasp. The lack of a comprehensive framework to investigate and understand this complex phenomenon hinders the design of optimal preclinical and clinical studies aimed at developing effective therapies in regenerative medicine. We study inflammation because this highly complex process is central to regeneration.
The Center
The Center for Inflammation and Regenerative Modeling was developed to address the need for a unified, systems framework to tackle the complexity of the inflammatory response — in the setting of regenerative medicine and beyond.
CIRM is headed by Dr. Yoram Vodovotz , Director and Associate Professor of Surgery and Dr. Gilles Clermont, Medical Director and Assistant Professor of Critical Care Medicine.
Integral parts of CIRM include its three cores: Modeling, Educational, and Data Analysis. This framework is designed to train interdisciplinary scientists in the emerging discipline of inflammation modeling, to characterize several scenarios of relevance to regenerative medicine, and to identify new therapeutic approaches.
Initial efforts in the field of inflammation modeling
The CIRM team includes clinicians, biologists, mathematicians, statisticians, and computer scientists engaged in a multidisciplinary effort to solve the puzzle of acute inflammation and organ failure in the setting of trauma and sepsis.
This team is carrying out an iterative program of model generation, verification, and calibration in both animals and humans, and subsequent hypothesis generation and testing in the setting of acute inflammation. Investigators have also incorporated mechanistic models of wound healing to create preliminary mathematical models of inflammation, organ damage and dysfunction, and wound healing.
CIRM has set three primary goals:
- To bring to bear on the problem of acute and chronic inflammation the interdisciplinary input and enthusiasm of clinicians, bench scientists, and modelers, from both research institutions and companies
- To facilitate the design of regenerative medicine approaches by elucidating the underlying inflammatory processes and the inflammatory impact of various therapies
- To understand and harness the intrinsic regenerative power of the human body by modeling not only specific organs but also the inflammatory communication network that binds them together
The McGowan Institute Scientific Retreat will be held on March 7-8, 2005 at the Nemacolin Woodlands Hotel. The meeting will provide unique opportunities for networking and collaboration amongst colleagues and new scientists, engineers and clinicians. Under the leadership of Timothy Billiar, M.D. the retreat program has been finalized and includes many distinguished speakers including:
- Elliot Chaikof, MD, PhD: Emory School of Medicine
- Toshiharu Shinoka, MD: Tokyo Women's Medical University
- Colonel Craig Shriver, M.D.. U.S. Army, Head of Surgery, Walter Reed Medical Center
We extend our appreciation to the Pittsburgh Tissue Engineering Initiative who is the senior sponsor of the Retreat. We also extend our thanks to Cook Myosite and RheoGene for serving as Retreat sponsors.
Program information is available at www.mirm.pitt.edu/events/retreat2005agenda.htm
The National Institute of Biomedical Imaging and Bioengineering (NIBIB) has recognized the pioneering research of Dr. Stephen Badylak that led to the discovery of a bioengineered tissue scaffold that promotes wound healing. The bioengineered material that he initially discovered 20 years ago is now playing a crucial role in treating conditions ranging from incontinence to burns. His discovery has evolved into a significant advance in tissue engineering, laying the groundwork for a host of new medical treatments.
The material which is derived from the small intestines of pigs is increasingly used by surgeons to restore damaged tissues and support the body’s own healing process.
Physicians rely on the material, called small intestinal submucosa (SIS), for everything from reconstructing ligaments to treating incontinence. Today, SIS is most commonly used to help the body close hard-to-heal wounds such as second-degree burns, chronic pressure ulcers, diabetic skin ulcers, and deep skin lacerations.
“About half a dozen new tissue engineering companies have capitalized on our findings and have helped translate NIH-funded research into medical devices that are treating patients,” says Dr. Stephen Badylak, who helped to discover the healing properties of SIS about 20 years ago.
Dr. Badylak’s team found that the extracellular matrix (ECM) of the small intestine was the key to successfully creating a biologic scaffold for tissue repair. The ECM consists of structural and functional proteins including many types of collagen, growth factors, and support molecules. Additionally, the team discovered that the ECM not only serves as nature’s starting point for tissue healing, but also supplies the foundation for wound repair. For instance, the team learned that ECM-associated molecules generated during wound healing have potent functions, helping to resist infection and recruiting tissue-building molecules for the site of injury.
SIS, for example, which relies on an extracellular matrix, can be configured into sheets, gels, powders, and multilaminate forms for orthopedic use and hernia repair. In its early stages, scientists engineered SIS primarily from a mechanical perspective. Researchers were looking for a material shaped like a tube, the size of blood vessels, and strong enough to be sutured while also sustaining the contraction and expansion of a pulsating artery. Scientists have since realized that engineering SIS from a biochemical standpoint is paramount. For successful healing to occur, the graft tissue must foster a molecular environment that can speed up the body’s own healing process.
Dr. Badylak’s quest for improvements in the technology and to expand the applications is being pursued through currently funded NIBIB research, where he is trying to understand the biomolecular, immunologic, anatomical, and biomechanical processes of SIS.
See the summary of Dr. Badylak’s discovery on the NIBIB web site.
The research findings of Dr. Andrew Schwartz represents big step toward development of brain-controlled artificial limbs for people. According to research presented at the 2005 American Association for the Advancement of Science (AAAS) Annual Meeting, McGowan scientists have made significant strides to create a permanent artificial device that can restore deliberate mobility to patients with paralyzing injuries.
The concept is that, through thought alone, a person could direct a robotic arm – a neural prosthesis – to reach and manipulate a desired object.
As a step toward that goal, Dr. Schwartz and his colleagues report that a monkey outfitted with a child-sized robotic arm controlled directly by its own brain signals is able to feed itself chunks of fruits and vegetables. The researchers trained the monkey to feed itself by using signals from its brain that are passed through tiny electrodes, thinner than a human hair, and fed into a specially designed algorithm that tells the arm how to move.
The neural prosthesis moves much like a natural arm, with a fully mobile shoulder and elbow and a simple gripper that allows the monkey to grasp and hold food while its own arms are restrained.
Computer software interprets signals picked up by tiny probes inserted into neuronal pathways in the motor cortex, a brain region where voluntary movement originates as electrical impulses. The neurons’ collective activity is then fed through the algorithm and sent to the arm, which carries out the actions the monkey intended to perform with its own limb.
The Schwartz Lab is now working to develop a prosthesis with realistic hand and finger movements. Because of the complexity of a human hand and the movements it needs to make, the researchers expect it to be a major challenge.
Congratulations to the following faculty:
• Dr. Badylak and Dr. Woo: recipients of Carnegie Science Center Awards for Excellence; presentation April 27, 2005
Finalists in the Pittsburgh Business Times “Heroes of Health Care Awards”; presentation March 10, 2005
• Dr. Badylak (Innovation & Research Category
• Dr. Herberman (Lifetime Achievement Category)
• Dr. Kormos (Physician Category)