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Yuchen Wang successful defends thesis

Wednesday, January 10, 2018

Recent PhD graduate Yuchen Wang successfully defended her thesis in January and is now employed at PaxVax as a Research Scientist. Yuchen’s research project was titled, "Development of Controlled Release Systems for Fracture-Targeted Therapeutic Delivery.”

Abstract:

Fracture healing is a major clinical challenge, with a 10-20% impaired healing rate, resulting in significantly prolonged hospitalization, decreased quality of life, and substantial healthcare costs. Currently, myriad therapeutics that target various mechanisms and signaling pathways have been developed to augment fracture healing. Apart from bone morphogenic protein (BMP) implants, there are currently no FDA approved fracture healing enhancement drugs on the market. A major challenge of the bench side to bedside translation is efficient drug delivery. This motivates the goal of this dissertation, which is to develop successful drug delivery systems that can overcome critical barriers to realize clinical translation. Drug delivery barriers to bone fracture enhancement therapies include short half-life in vivo, non-specific accumulation in healthy tissue, as well as associated side effects. The studies herein provide strategies for local and systemic drug delivery. Specifically, the local delivery system in this thesis consists of polymer-based hydrogels loaded with siRNA/nanoparticle (NP) complexes. The local drug delivery system takes advantages of the NP’s ability to protect siRNA and facilitate cell uptake, and the hydrogel’s ability to localize and sustain the encapsulated content at the fracture site. Results showed controlled release of siRNA/NPs complexes from hydrogels through hydrolytic degradation. Localization of NPs at fracture was associated with degradation rates of hydrogels such that hydrogels with the slowest degradation rates yielded longer localization at fracture. Hydrogels that delivered siNRA/NP for ~ 1 month were implanted in a murine fracture model, and in vivo gene silencing efficiency indicated potent and expedited healing. In the systemic drug delivery system, polymeric NPs with bone-targeting peptides conjugated onto the NP corona were used to realize bone targeting efficacy. Potent fracture-targeting efficiency was observed, and NPs accumulated at fractures for ~ 7 days. NPs loaded with a small molecule GSK-3β inhibitor and showed fracture site-specific β-catenin agonism, enhanced bone mechanical properties, and faster healing rates. Taken together, the two drug delivery strategies explored here establish solid platforms for design of next generation drug delivery systems to fracture.

Maureen Newman will be recognized for her research at 2018 Annual ORS Conference

Tuesday, January 2, 2018

Maureen Newman will be honored for her work titled, "Development of Bone-Targeted Polymer Conjugates of Wnt/β-Catenin Agonists to Stimulate Fracture Healing" during the spotlight session at the 2018 Annual Orthopaedic Research Society (ORS) Conference on March 10th, 2018 in New Orleans, Louisiana.