Helping the Body to Heal Itself

New Program Advances Research in Tissue Engineering

Tissue engineering is a rapidly growing field that seeks to restore the function of injured or diseased tissue by either stimulating the body to repair itself or regenerate new tissue, or by replacing damaged tissues with healthy cells and tissues grown outside the body. By harnessing the body’s ability to heal itself, tissue engineering promises to vastly improve treatment options for numerous injuries and illnesses.

Hospital for Special Surgery recently created the Tissue Engineering, Regeneration, and Repair Program to advance understanding of how to apply tissue engineering techniques to treat patients plagued by injuries to the musculoskeletal tissues, which include cartilage, meniscus, ligaments, tendons, bone, and skin. Directed by Senior Scientist Peter Torzilli, PhD, the goal of the Program is to understand the fundamental processes underlying the development, damage, degeneration, and healing of musculoskeletal tissues and to use this information to develop new strategies to prevent, repair, regenerate, or replace the injured tissues.

Laboratory of Soft Tissue Research Anchors New Program
Dr. Torzilli has been at HSS for 30 years studying the function, repair, and replacement of soft tissues. In 1992, he co-founded the Laboratory of Soft Tissue Research with Surgeon-in-Chief Emeritus Russell F. Warren, MD, and Director of Orthopaedic Research Jo A. Hannafin, MD, PhD. Over the years, discoveries emanating from the laboratory have advanced progress toward better treatments for soft tissue injuries that promise to reduce patients’ pain and restore their mobility. Today, the Laboratory is an integral part of the new Tissue Engineering, Regeneration, and Repair Program and is rapidly expanding to explore how scientists can use normal and synthetic biological pathways, gene therapy, and biomaterials to repair, restructure, or replace damaged soft tissue.

Improving Treatment, ACL Injuries
For the past 15 years, Dr. Hannafin’s work has been focused on improving treatment for injuries to the anterior cruciate ligament (ACL), a major supporting structure in the center of the knee. As a surgeon, Dr. Hannafin has seen first-hand the serious impact of injuries to this crucial ligament. “Losing this ligament causes instability to the knee and can lead to the development of other problems, including meniscus tears, cartilage degradation, and ultimately the development of early arthritis,” explained Dr. Hannafin.

Recently, Dr. Hannafin received a $1.3 million grant from the National Institutes of Health to fund her investigation of signal transduction pathways in the ACL, which promises to increase our understanding of how to stimulate its repair or regeneration. “The problem with the ACL is that when it tears, it commonly shrivels up and eventually disappears,” explained Dr. Hannafin. “My work is focused on understanding the biologic and biomechanical signaling pathways in the cells of the ACL that signal them to produce the enzymes that cause this involution,” she continued. “Understanding this process may enable us to intervene to prevent the involution of the ACL and ultimately allow us to successfully repair the ligament. Understanding these signal transduction pathways may also improve our ability to optimize the function and healing of ACL grafts.”
 
Wound Healing Expert Recruited
An important step in the Tissue Engineering, Regeneration, and Repair Program’s growth was the recent recruitment of Marjana Tomic-Canic, PhD, from New York University School of Medicine. As the Director of the new Laboratory of Tissue Repair, Dr. Tomic-Canic is working to understand the molecular mechanism of wound healing and its pathogenesis in the skin, which has broad application to the healing of musculoskeletal tissues.

“During embryogenesis, parts of skin (dermis), cartilage, and bone all derive from the same origin,” explained Dr. Tomic-Canic. “These tissues also share similar composition that consists of matrix and cells. Therefore, cellular processes that guide their repair mechanisms have many common properties and similar therapeutic approaches may be applicable.” For example, tissue-engineered scaffolds are currently being used in patients with chronic ulcers to enable them to “grow” skin to close the wounds. Similarly, Assistant Scientist Suzanne Maher, PhD, who heads the Laboratory for Functional Tissue Engineering, is investigating the use of scaffolds made of hydrogels, to repair damaged cartilage by providing a matrix in which embedded growth factors stimulate the proliferation and migration of healthy cells to the affected areas.

Building for the Future
Since the goal of tissue engineering is to restore or replicate normal tissue functioning in compromised individuals, it is necessary for tissue engineering researchers to understand the origin, development, and maintenance of normal tissue. In order to accomplish this, Special Surgery’s Tissue Engineering, Regeneration, and Repair Program is planning to expand in the areas of developmental biology, mesenchymal (adult) stem cells, and cell-matrix signaling. Dr. Torzilli explained that, “Study in these areas will enhance our ability to develop strategies to repair, regenerate, and replace tissues by helping us address critical questions like: How do tissues develop and grow and how do mechanical forces affect these processes? How can we direct stem cells toward a particular developmental pathway to yield specific types of differentiated cell populations? How do cells and matrix communicate in such a way that cells are prompted to produce a specific kind of tissue?”

An Interdisciplinary Approach
Drs. Torzilli, Hannafin, Tomic-Canic, and Maher are joined by Scott A. Rodeo, MD, who is focused on tendon-to-bone healing, as well as Chris Chen, PhD and Chisa Hidaka, MD, both of whom are investigating cartilage repair and regeneration. By bringing together interdisciplinary teams of scientists, physicians, and engineers, the Tissue Engineering, Regeneration, and Repair Program exemplifies Special Surgery’s commitment to collaborative medicine, which promises to accelerate the pace of discovery and more rapidly translate breakthroughs into improved treatments for patients.

Dr. Torzilli is particularly excited about the Program’s collaboration with Special Surgery’s immunologists to explore how mechanical forces and the inflammatory process interact to affect orthopedic problems, an emerging area of research he has termed “mechanoimmunology.” “We are becoming increasingly cognizant of different influences in the musculoskeletal system,” explained Dr. Torzilli. “Every tissue in the body is to some degree altered by the mechanical load it experiences,” he continued. “Changing the shape of a tissue may profoundly impact the way that it responds to inflammation and other processes. Understanding this interaction has the potential to dramatically improve our ability to prevent and treat arthritis and many other musculoskeletal illnesses.”

Nurturing the Next Generation of Tissue Engineering Researchers
In addition to conducting research, the Tissue Engineering, Regeneration, and Repair Program strives to mentor students in the scientific, medical, and engineering principles necessary to advance their careers. “By giving promising young students the chance to see what it is like to work in a laboratory and learn about research by actually doing it, the Program is helping to develop the next generation of tissue engineering researchers,” explained Dr. Peter Torzilli, the Program’s Director.

Over the past year, Karla Wyatt, a Biomedical Engineering (BME) student working toward her Master of Science degree at City College, has been interning in the Program. Originally from Syracuse, New York, Karla earned her B.S. in Electrical Engineering from North Carolina Agricultural and Technical State University. Under Dr. Torzilli’s guidance, Karla has been investigating the effects of tensile strength on the degradation of Type I Collagen, a process which occurs during the onset of arthritis.

“The opportunity to combine my engineering background with my interest in medicine was what initially attracted me to the Program,” explained Karla. “Having the chance to see first-hand how scientists use biological and mechanical techniques to understand disease has been by far the best part of my experience,” she added. Karla intends to pursue her interest in tissue engineering and is currently applying to Biomedical Engineering MD-PhD joint degree programs.

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