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Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

Award Number: R03DE028631
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	2	4/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	2	11/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	2	9/16/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $236,830 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	001	2	1/5/2021	SUPPLEMENT FOR EXPANSION	$84,252
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	002	2	2/23/2021	NON-COMPETING CONTINUATION	$15,258
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	2	11/19/2020	NON-COMPETING CONTINUATION	$137,320
														Subtotal = $236,830

Issue Date FY: 2020 ( Subtotal = $152,727 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	1	11/29/2019	NEW	$152,727
														Subtotal = $152,727

Grand Total All Awards = $389,557

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Nutrient-Derived Alloys with Nanostructured Surfaces for Distraction Osteogenesis

Award Number: R03DE028631

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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