Project Summary Local delivery of growth factors has been applied to treat various human diseases. However, many growth factor delivery systems cannot stably sequester bioactive growth factors for sustained delivery, primarily due to a lack of high-affinity and high-specificity molecular recognition. This deficiency leads to the rapid release of growth factors, thereby requiring supraphysiological levels of drug loading and delivery to achieve therapeutic efficacy. Unfortunately, such a delivery approach has been found to cause high toxicity and even cancer in patients. Therefore, the objective of this project is to study a novel transformative drug delivery platform based on non- covalent functionalization with bispecific aptamers. Different from traditional methods requiring co-valent functionalization, this innovative method does not require alterations to the manufacturing procedures or properties of existing biomaterials. Furthermore, growth factors can be loaded into off-the-shelf biomaterials when needed. To achieve the goal, we will: 1) design and evaluate bispecific aptamers; 2) evaluate growth factor loading and release; and 3) evaluate in vivo growth factor delivery. It is anticipated that bispecific aptamers can stably attach to delivery systems and sequester growth factors due to high binding affinities and specifities, allowing for local, sustained growth factor delivery. The success of this project will not only lead to the development of a technological platform for growth factor delivery, but also transform the way of functionalizing various materials at different scales in applications such as bioimaging, biosensing, cell engineering, etc.