McGowan Institute for Regenerative Medicine
deputy director Stephen Badylak, DVM, PhD, MD (pictured), professor in the Department of Surgery and director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute, and his research on the healing properties of extracellular matrix (ECM) were named by The Wall Street Journal
as heralding one of the latest scientific advances expanding the span of human life. In her article, “Living to 100 and Beyond,” author Sonia Arrison explains, “For as long as human beings have searched for the fountain of youth, they have also feared the consequences of extended life. Today we are on the cusp of a revolution that may finally resolve that tension: Advances in medicine and biotechnology will radically increase not just our life spans but also, crucially, our health spans.”
Dr. Badylak’s laboratory is a highly interdisciplinary environment. The major focus of the laboratory is the development of regenerative medicine strategies for tissue and organ repair or replacement. The use of mammalian ECM or its derivatives as an inductive template for constructive remodeling of tissue is a common theme of most research activities. The central and most important objective of all projects is clinical translation and improved patient care. Several current clinical studies of ECM include:
- Restoration of functional limb and digit tissue
- Esophageal repair
- Muscle tissue regeneration
By recruiting cells for regeneration, Dr. Badylak's team is investigating the possibility of regenerating digit tissue using ECM that promote and stimulate the body's regenerative capacity. The restoration of functional limb and digit tissue involves the orchestrated growth and differentiation of multiple tissue types in a spatially appropriate and site appropriate pattern. A logical and rational, albeit challenging, approach is the development of strategies and methods that can recapitulate the processes that occur during fetal development or the phenomenon of epimorphic regeneration that occurs in urodeles and many amphibian species. These processes involve the formation of epimorphine regeneration, a process which involves the accumulation of multipotential progenitor cells at the site of the remodeling ECM. These cells then, in response to local environmental tissue signals, proliferate, differentiate, and spatially organize into a functional tissue to replace the lost body part.
It should be noted that some of Dr. Badylak’s research has matured to the point that clinical trials are feasible, while the more complex applications are still the subject of research that may require many additional years of study.
In clinical trauma research, the U.S. Army's Institute of Surgical Research (ISR) is examining a variety of combat casualty care problems in trauma patients. ISR is recognized worldwide for its contributions to improved trauma survival. In partnership with the ISR, Dr. Badylak's ECM technology is being evaluated today to help partially ameliorate soldier limb and digit amputation wounds. The project has a digit extension goal of 1 centimeter in length. The study is led by Steven Wolf, MD, at ISR and is currently limited to injured military personnel.
In Buenos Aires, under the leadership of McGowan Institute for Regenerative Medicine faculty member Alejandro Nieponice, MD, PhD, research assistant professor in the Department of Surgery, the director of minimally invasive esophageal surgery at Fundación Favaloro, as well as a surgical associate and director of the Clinical Translation Unit at the Austral University Hospital in Buenos Aires, Argentina, a clinical translation program for regenerative medicine is running in partnership with the McGowan Institute. Dr. Nieponice has treated several patients with ECM for esophageal applications.
Hiatal hernia repair is a frequent procedure in western countries as treatment for reflux disease and ECM scaffolds are becoming routinely used to prevent recurrence. ECM has been successfully used where other options had previously failed, like closures of esophageal fistulae or repair of esophageal strictures.
Massive loss of musculotendinous tissue as a result of trauma inevitably leads to serious patient morbidity, surgical challenges for the repair of such injuries, and/or amputation of the affected limb if surgical approaches prove to be untenable. A loss of tissue mass in the gastrocnemius muscle, quadriceps, biceps or triceps, or hamstring muscle group can pose significant surgical challenges. Free muscle grafts, pedicle grafts, and the use of prosthetic materials have all been attempted when primary repair is impossible due to loss of tissue domain; the results of such efforts are typically much less than satisfactory. When autologous grafts are used, donor site morbidity compounds the post surgical problems for the patient and a diminished quality of life follows. Stated differently, existing treatment options for loss of large masses of muscle tissue domain have very limited therapeutic options. A regenerative medicine approach that could reconstitute functional musculotendinous tissue, and by implication include adequate vascularization and innervation, would represent a paradigm shift in the treatment of traumatic tissue injury. The proposed approach of a study led by Dr. Badylak involves the use of an "off the shelf" biologic scaffold material that would replace the missing soft tissue, initiate a stem/progenitor cell recruitment process, and facilitate site appropriate functional tissue restoration. The study is lead by Steven Wolf, MD, at ISR and is currently limited to injured military personnel.
Future clinical studies will follow ECM research projects focused on the development of bioscaffolds for liver and heart regeneration and regenerative medicine for temporomandibular joint (TMJ) disc reconstruction.
The Wall Street Journal (08/27/11)
Stephen Badylak Laboratory
Clinical Translation: Inductive Scaffold for Digit Extension
Clinical: Esophageal B. A.
Clinical Translation: ECM-Replacement of Lost Muscle Tissue
Bio: Dr. Stephen Badylak
Bio: Dr. Alejandro Nieponice