Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

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Project Summary Defects in craniomaxillofacial (CMF) skeleton affect thousands of babies every year in the United States. For repairing moderate to severe bone deficiency, a surgical technique called distraction osteogenesis (DO) is fre- quently used to gradually lengthen abnormal bones in pediatric patients. In contrast to external devices, internal distraction devices (IDD) implanted directly to the bone are safer to wear for a period of several months, more comfortable to the patients without social discomfort, and, therefore, permit greater retention periods, which provide better long-term stability than external devices. However, their major disadvantage is that they require a second invasive operation under general anesthesia for device removal. Moreover, infections of distraction de- vices cause poor bone growth and complications that require additional revision surgeries. This project will pro- vide a promising solution of bioresorbable antimicrobial devices that eliminate the secondary surgeries and in- fection-induced complications, thus improving clinical outcome. The PI has engineered a new class of Mg alloy via coupling biocompatible nutrient elements Mg, zinc (Zn) and calcium (Ca) with novel alloy processing and surface treatment, which not only provide the needed mechanical and degradation properties, but also induce desirable cellular responses for bone growth and antimicrobial property. The PI has demonstrated antibacterial property and bioactivity of the new Mg alloys with nanostructured surfaces in vitro using pathogenic bacteria and relevant bone marrow cells. The objective of this project is to fabricate a model internal distraction device (IDD) using the crystalline Mg-Zn-Ca alloys coupled with nanostructured surfaces and verify the antibacterial property, bioactivity, biocompatibility, and mechanical properties in vivo. The central hypothesis is that the IDDs made of the bioresorbable alloys with nanostructured surfaces will reduce bacterial adhesion and viability in vivo while meeting the requirements of mechanical properties and bioactivity for distraction osteogenesis (DO), built on the PI’s prior results and positive effects of Mg, Zn, and Ca as essential nutrients for bone repair and immune system health. This project is innovative because the alloy design, processing, and nanostructured surface treatment synergize biological benefits with materials science tetrahedron to achieve integrated mechanical and biological properties. Further, the approach for creating infection-free IDDs is innovative because it does not rely on anti- biotics, and reduce the emergence of antibiotic-resistant bacteria. This project is significant because it will over- come the critical knowledge gap on the in vivo interactions of bioresorbable IDDs with bacteria, crucial bone cells and immune cells, and thus advance the new devices toward preclinical studies and clinical translation. This research will lead to new solutions for repairing CMF bone deformities in children and eliminating device-asso- ciated complications.