Controlled Growth Factor Delivery By Mechanical Stimulation
- PDF / 114,088 Bytes
- 4 Pages / 612 x 792 pts (letter) Page_size
- 43 Downloads / 189 Views
Controlled Growth Factor Delivery By Mechanical Stimulation
Kuen Yong Lee, Martin C. Peters, Kenneth W. Anderson, and David J. Mooney Dept. of Biologic & Materials Sciences, Chemical Engineering, and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, U.S.A.
ABSTRACT Growth factor delivery using polymer matrices is one exciting approach to replace or regenerate tissues. Most growth factor delivery systems, however, have been designed to operate under static conditions, regardless of dynamic environments in the body. Considering the dynamic environment of our body (e.g., bone, muscle, and blood vessel), mechanical stimulation is an important signal that could be readily exploited. We hypothesize that polymer matrices, which release growth factors in response to mechanical stimulation, could provide a novel approach to engineer tissues in mechanically stressed environments. We report here a model system, comprised of alginate hydrogel and vascular endothelial growth factor (VEGF), which upregulates the release of the growth factor in response to mechanical stimulation and subsequently promotes granulation tissue formation in animals. This approach may find a number of potential applications in tissue engineering, as well as in drug delivery.
INTRODUCTION Controlled growth factor delivery from polymer matrices has found numerous advantages in cell transplantation and tissue engineering [1]. These advantages include high efficiency, precise dose control, reduced toxicity, and convenience to the patient compared to the conventional methods such as intravenous bolus injection and tissue injection [2]. Most growth factors are inherently instable when administered via bolus injection or tissue injection, probably due to the proteolytic degradation by digestive enzymes in the body, and the administration often must be repeated. In contrast, controlled delivery systems using polymer matrices can potentially maintain the bioavailability of protein growth factors for prolonged time periods. Extracellular matrices of tissues are regarded as depots of various growth factors, which are released to cells in the surrounding tissue to affect a variety of physiologic processes. Many synthetic and naturally derived polymers can be similarly used as depots and delivery vehicles of protein growth factors [3]. A potential limitation of current delivery systems, however, is that they have been designed to operate under static conditions, irrespective of dynamic environments in the body. Many researchers have attempted to develop delivery systems, actively responding to external stimuli such as temperature, pH, ultrasound, electric or magnetic fields [4]. However, mechanical signals have not been systematically exploited yet as an external stimulation for controlled growth factor delivery, regardless of its simple but critical function in the body (e.g., compression in cartilage and bone, tension in muscle and tendon, and shear force in blood vessels). In this context, we hypothesize that the interaction of growth factor
Data Loading...
