This Career award to University of Delaware is funded by the Biomaterials program in the Division of Materials Research. With this project, the PI will develop biomaterials that closely resemble the structural organizations and multi-scale responsiveness of the natural extracellular matrices, but with controlled architectures and improved mechanical properties. Main focus of the proposed study will be: 1) design of mechano-responsive hydrogels by covalent cross-linking of polyethylene glycol with nanoparticles exhibiting sacrificial bonds and hidden length on their surfaces to mimic the modular domain structures present in functional proteins; 2) synthesis of mechano-responsive elastomers by recapitulating the molecular architecture of natural elastin whereby the hydrophobic domain of the native elastin is replaced with a synthetic polymer that is capable of elastic recoil, while the hydrophilic domain will be replaced with specific peptide sequences with potential structural directing capability; and 3) characterization of mechanical properties of these dynamic and modular biomaterials by microscopic and macroscopic methods. Although smart biomaterials have been designed to respond to external stimuli such as pH, temperature, reagents, electrical or magnetic fields, synthetic polymers with the ability to respond rapidly and reversibly to mechanical stresses over prolonged periods of time in the human body have yet to be developed. Given the fact that most tissues in the body are subjected to mechanical stimuli, and cells within the tissues have sophisticated machinery that actively responds to the mechanical force, it is critical that this form of signaling will be considered in the design of polymeric matrices in this project.
The proposal aims to educate several graduate and undergraduate students in biomaterials and integrates them with PI's research interest in mechano-responsive biomaterials. Developing a new graduate level course in biomedical engineering to teach biomaterials/biomedical concepts to students and stimulate their interest in these areas is also part of this project. The educational component is closely integrated with the proposed research activities with the goals of inspiring high school students to pursue biomaterials/biomedical careers; and providing research opportunities for under-represented minority students with hands-on experiences in biomaterials research. The interdisciplinary nature of the proposed research and education activities will also equip graduate students with up-to-date information, experimental skills, and creative thinking that are all indispensable in the growing field of biomedical engineering. The ultimate goal is to establish research and education programs that will not only advance the field of biomedical engineering by generating biomaterials with unprecedented mechanical properties and responsiveness but also to inspire and educate the next generation of biomedical engineers and scientists.
Normal 0 false false false EN-US X-NONE X-NONE The goal of the CAREER project is to develop smart, responsive materials for biomedical applications. Over the past few decades, smart materials that dramatically change their shape and properties in response to environmental factors, such as temperature, pH, light, and other chemical and electrical signals have been extensively investigated. One universal stimulus present in the biological world is mechanical force, and materials that respond to mechanical loading conditions present in the human body have not been engineered. The CAREER award has enabled the development of two types of novel materials that are mechanically robust and mechanically responsive. The first type of material is a soft and pliable hydrogel that, when compressed or stretched, releases medications on demand. This is achieved by mimicking the reversible folding/unfolding of domain structures in proteins found in the human body. In our system, the mechanical forces applied to the hydrogel are transmitted to nanoscale drug depots integrated in the hydrogel networks, resulting in an accelerated release of the entrapped anti-inflammatory drug molecules. The second type of material is a hybrid polymer that mimics the composition, structure and organization of natural elastin. The hybrid polymers are constructed by linking peptides, identified from the natural elastin, with FDA-approved synthetic polymers in an alternating fashion using an efficient chemical reaction. The modular nature of the synthesis allows facile adjustment of the peptide sequence and the polymer composition to modulate the structural and the mechanical properties of the hybrid polymers. When the peptide sequence is derived from the crosslinking regions of elastin, the crosslinked hybrid polymer can be easily stretched and readily bounces back when force is removed. On the other hand, when the peptide sequence is derived from the hydrophobic regions of elastin, the hybrid polymers organize themselves into nanosized spherical particles. Our hybrid polymers offer a versatile platform for mechanistic understanding of the structure and properties of elastin. In summary, our innovation has led to the development of reliable synthetic and engineering methodologies for producing unique mechano-responsive biomaterials that not only capture the modular structures of natural polymers, but also exhibit more improved mechanical properties than the existing synthetic biomaterials. The mechano-responsive materials developed in this project have the ability to convert mechanical forces to biochemical signals to mediate cellular functions during wound healing and tissue repair, offering powerful alternative treatment methods for patients suffering from debilitating diseases. These materials are currently being tested as alternative treatments for osteoarthritis and vocal fold scarring. Our work has been summarized in various publications (13 total) in scientific journals. This award has supported 2 postdoctoral researchers (both female), 2 PhD students (1 female) and 6 undergraduate students (2 female, 2 underrepresented minority). Discoveries made from this project have been integrated in multiple hands-on lab demonstrations to K-12 students. Results collected from this project have also been incorporated in graduate/senior undergraduate level biomaterials courses at the University of Delaware.
