Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

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Project Summary Distraction Osteogenesis (DO) is a technique for repairing moderate to severe congenital and acquired cra- niomaxillofacial (CMF) skeletal deformities. Distraction devices are frequently used to secure and elongate the bones where an osteotomy is created purposely, and allow the body's natural osteogenic processes to produce new bone to fill the expanding gap at 1-3 mm/day. In contrast to external devices, internal distraction devices (IDD) are implanted directly to the bone, are more comfortable to wear for a long period of several months without social discomfort, and permit greater retention periods, which lead to better long-term stability than external devices. However, the major disadvantage of IDD is that they require a second invasive operation under general anesthesia for device removal, because current IDDs are made out of non-degradable titanium (Ti) alloys. IDDs of degradable polyesters such as poly-L-lactic acid (PLLA) and derivatives have been attempted, but clinically abandoned because their inherently lower mechanical strength than that of metals caused premature collapse of device. Moreover, distractors normally protrude through the skin for turning and thus face a higher risk for infections. Infection-induced poor bone growth and complications require systemic administration of antibiotics and often additional revision surgeries. This project will provide a promising solution of bioresorbable antimicro- bial devices that eliminate the secondary surgeries and infection-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 anti- microbial 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 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 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 mechan- ical and biological properties. This project is significant because it will overcome the critical knowledge gap on the in vivo interactions of bioresorbable IDDs with bacteria, crucial bone cells and immune cells, demonstrate load-bearing capacity of bioresorbable IDDs, and thus advance the new devices toward clinical translation. This research will lead to new solutions for repairing CMF bone deformities and reducing complications.