Biomimicry and Regenerative Therapeutics

Regenerative medicine holds great hope for patients in the future, and two accomplished researchers discussed their work in the field at the March 25 Forum at the Beth Israel Deaconess Medical Center.

Jeffrey Karp, PhD, spoke on “Biomimicry: Nature as Model, Measure and Mentor.” He is an instructor in medicine and health, science and technology at Harvard Medical School and Brigham and Women’s Hospital; and director, Laboratory for Advanced Biomaterials and Stem Cell-based Therapeutics, BWH.

Moderator for his presentation was Frederick 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; and CIMIT site miner at BWH.

Presenting on the topic of “Steering Stem Cells to Treat Osteoporosis,” was Robert Sackstein, MD, PhD, associate professor of dermatology and of medicine, Harvard Medical School; head, the Translational Research Program of the Bone Marrow Transplantation Unit, Massachusetts General Hospital; Bone Marrow Transplant Physician at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute.

Moderator was Charles 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.

Dr. Karp discussed his work in the field of biomedical adhesives using nano and microscale approaches. Much of his study is based on understanding the mobility of the gecko, a form of lizard. He said geckos attach to smooth vertical surfaces and support their weight on a single toe. Dr. Karp indicated this principle could be useful in understanding that evolved designs in nature offer opportunities for advances in biomedical engineering.

He also discussed the creation of materials to capture cells mimicking the vascular endothelium’s ability to initiate cell rolling in viscous shear flow. Surface engineering through covalent immobilization of selectins can achieve long-term precise control over cell rolling, which may be useful for capturing and separating cells for diagnostic and therapeutic applications.

Dr. Sackstein discussed the notion that successful clinical implementation of stem cell-based regenerative therapeutics depends on the ability to deliver stem cells to sites where they are needed. His lab has developed a platform technology called "glycosyltransferase-programmed stereosubstitution,” or GPS, for custom-modifying CD44 glycans to create HCELL (hematopoietic cell E-/L-selectin ligand) on the surface of living cells. He suggested GPS technology could have major implications in therapy of generalized bone diseases such as osteoporosis, and may also be exploited for stem-cell based regenerative therapeutics for non-skeletal diseases.

Biomimicry - Nature as Model, Measure and Mentor

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.            

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