Biomimicry and Regenerative Therapeutics

4:00PM Biomimicry - Nature as Model, Measure and Mentor
Jeffrey Karp, PhD, Instructor in Medicine and Health Sciences and Technology, Harvard Medical School, Brigham and Women's Hospital; Director, Laboratory for Advanced Biomaterials and Stem-Cell-Based Therapeutics, BWH, jmkarp@partners.org

Moderator: Frederick J. Schoen, MD, PhD, Professor of Pathology and Health Sciences and Technology, Harvard Medical School; Director of Cardiac Pathology and Executive Vice-Chairman,Department of Pathology, Brigham and Women’s Hospital, CIMIT Site Miner, BWH, fschoen@partners.org

Nature has produced many amazing systems that scientists are beginning to use as inspiration for novel biomedical devices. One fascinating piece of natural engineering can be seen in the foot of the gecko, where each toe is sticky enough to support the lizard’s entire bodyweight. Researchers in the lab of Jeffrey Karp, PhD, of Harvard Medical School are attempting to mimic structures found in the gecko’s foot in order to create a biomimetic tissue adhesive. Such an adhesive would be very useful in the correction of hernias, in gastric bypass surgery, and in laparoscopic procedures. It would be quicker to apply than conventional sutures and would hopefully improve patient outcomes by making surgeries shorter. In the gecko’s foot, adhesion is the result of tiny nanofeatures that increase the surface area of the foot to such an extent that normally negligible contact forces (van der Waals forces) become significant. One challenge involved in translating gecko-style adhesion into the human body is the fact that water molecules gum up the nanofeatures and prevent the adhesive from sticking. To get around this problem, Karp’s team has come up with an adhesive that combines physical structures with chemical adhesives. Their adhesive consists of 1-um hairs coated with a very thin layer of glue. They found that their adhesive was significantly stickier than the glue alone. In a proof of concept experiment, they tested the adhesive in living rats and found that it caused only mild inflammation and exhibited good long-term stickiness.

Another project in the Karp lab is to create a device capable of destroying tumor cells circulating in the blood. Their device is based on leukocyte rolling, which occurs naturally in the blood stream. Leukocytes, or white blood cells, travel to sites of inflammation through the vascular system, and when they leave the blood stream to enter tissues, they first roll along the vascular endothelium in order to slow down. This rolling is facilitated by endothelial adhesion proteins called selectins, which bind and unbind to ligands on the leukocyte surface. Researchers in Karp’s lab are attempting to build a nanodevice in which cancer cells will roll and simultaneously receive a signal to undergo apoptosis, or cell death. They have already built an epoxy surface with covalently attached p-selectins (a class of selectins). Using microscopy, they have observed that living cells such as neutrophils roll along the epoxy surface. To target cancer cells, they plan to attach TRAIL (Tumor-necrosis-factor-Related Apoptosis-Inducing Ligand) to their surface, with the hope that TRAIL will induce cell death in tumors rolling along the surface. In the future, devices built to promote cell rolling may be used to treat cancer and to provide valuable diagnostic information. View this presentation

4:50PM Steering Stem Cells to Treat Osteoporosis
Robert Sackstein, MD, PhD, Associate Professor of Dermatology and of Medicine, Harvard Medical School; Head of the Translational Research Program of the Bone Marrow Transplantation Unit, Massachusetts General Hospital and the Dana-Farber Cancer Institute, rsackstein@partners.org

Moderator: Charles A. Vacanti, MD. Anesthesiologist-in-Chief, Leroy D. Vandam/Benjamin G. Covino, Professor of Anaesthesia, Harvard Medical School; Director, Laboratories for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital, cvacanti@partners.org

As the median age of the world population increases, degenerative diseases will become more common, and regenerative therapy will become increasingly important. Osteoporosis, a disease characterized by thinning of the bones, affects around 300 million people worldwide and may affect one billion people by 2050. In patients with osteoporosis, bone fractures are common and sometimes even lethal. Contrary to what one might think, the bones in one’s body are always changing and are always being renovated. Osteoporosis occurs when osteoclasts, cells that destroy bone, become more active than osteoblasts, cells that create bone. Osteoblasts develop from mesenchymal stem cells, and the number of mesenchymal stem cells in the body decreases with age. Certain researchers have attempted to boost the body’s supply of stem cells by locally injecting stem cells, but this technique leaves much to be desired. It can damage tissue, and it cannot be used to treat diseases in hard-to-reach organs or systemic diseases such as osteoporosis. In almost all cases, it would be safer and more effective to allow stem cells to reach their destinations via a vascular route.

Researchers in the lab of Robert Sackstein of Harvard Medical School are attempting to come up with a way to direct mesenchymal stem cells to the bone marrow. Their system is based on the fact that the bone marrow constitutively expresses e-selectins, a group of adhesion proteins. A potent ligand for e-selectins is HCELL, or hematopoietic cell E-/L-selectin ligand. HCELL can be made from the transmembrane glycoprotein CD44 by adding a few sugar molecules. Like most cells, mesenchymal stem cells express CD44 but do not express HCELL. Dr. Sackstein’s team has developed a method called glucosyltransferase-programmed stereosubstitution (GPS) that uses non-toxic enzymes to convert CD44 into HCELL. Mesenchymal stem cells subjected to GPS become tagged for absorption in the bone marrow. Dr. Sackstein’s group has found that injecting human HCELL-bearing mesenchymal stem cells into mice results in the homing of these cells to the bone marrow and in the subsequent deposition of human bone. The GPS method being developed in the Sackstein lab will hopefully lead to a regenerative therapy for osteoporosis. The technique could also be used, with modifications, to target stem cells to a variety of tissues, and its simplicity may someday enable it to be used in the third world.

View this presentation