Diversity Supplement to Tissue Engineering Strategies to Revitalize Allografts

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Abstract: The goal of this Diversity supplement is the training of Sandra Castillo Aguirre. Specifically, her training will be undertaken via the research plan proposed. The work focuses on nanomaterials for bone regeneration, specifically to enhance the revitalization of bone allografts. Delayed union or nonunion, graft remodeling and repair, and metabolic bone diseases present critical needs for development of new technologies to enhance skeletal healing. While recent data reveal that Wnt signaling is essential for postnatal bone regeneration, delivery of Wnt agonists to support or enhance these endogenous mechanisms are limited due to short duration of action and off-target effects. Thus, a critical technological gap exists in developing specific drug delivery approaches for osteoprogenitors to modulate bone regenerative processes. Therefore, this work seeks to develop bone-selective nanomaterials designed to control Wnt agonist delivery and enhance bone regeneration in allograft-mediated reconstruction of massive bone defects. Our objective within this program is to (1) establish polymer nanotherapeutic requirements for targeting of remodeling bone allografts, (2) determine the required dose and longevity of osteoregenerative drug delivery to achieve cellular recruitment and bone regeneration in vitro, and (3) establish the regenerative efficacy of the drug delivery system in critical-sized bone defects. We hypothesize that resorption site-specific stimulation of bone regeneration can be achieved via targeted polymer therapeutic delivery of osteoanabolic Wnt agonists. The rationale for this work is to identify translatable therapies to selectively deliver osteoanabolic drugs to enhance bone regeneration. The long-term impact of this work is the development of polymer nanotherapeutics to target drugs to bone with high efficacy and specificity to promote bone graft healing and to rigorously train an underrepresented minority researcher in the field of therapeutic biomaterials and orthopaedic research.