This K99/R00 Mentored Research Career Development Award application is being submitted to the National Institute on Dental and Craniofacial Research (NIDCR). The candidate, Dr. Vuk Uskokovic, is a physical chemist and nanotechnologist who seeks to obtain additional training in the area of cell culture experimentation and other biological methods of analysis through this award.
His aim i s to develop research skills in the area of multifunctional and nanostructured biomaterials for reparation of hard tissues. The goals of this proposal would enhance Dr. Uskokovic's knowledge of fabrication of smart biomaterials for simultaneous time-controlled drug release and regeneration of diseased hard tissues. Proposed is the synthesis of calcium phosphate/polymer composite particles that encapsulate clinmadycin, a drug used in the treatment of osteomyelitis, as well as testing of the antimicrobial properties and osteinductive performance of the given material in vitro. The central hypothesis of the proposed study is that stoichiometry and the particle size of calcium phosphates can be used to tune the kinetics of the release of the encapsulated drug. Dr. Uskokovic will conduct his training and research activities under the guidance of an expert mentoring team that includes Drs. Tejal Desai, Grayson Marshall, Stefan Habelitz, Wu Li, and Peter Loomer. He will receive additional consulting from Drs. Mauro Ferrari, Antoni Tomsia, and Charles Hoover. Given that bioengineering and biomaterials research approaches to regeneration of oral and craniofacial tissues has been selected as one of the prioritized goals by the NIDCR (Objective I-5, Goal 1, NIDCR Strategic Plan 2009-2013), the goals of the current application will address highly actual oral, dental and craniofacial health problems. Training Dr. Uskokovic through this Pathway to Independence Award on top of his expertise in materials science and engineering and support by the UCSF Dental School, the most funded one by the NIH in the past 15 years, also complies with all three objectives of Goal 2 of the NIDCR Strategic Plan. Dr. Uskokovic will conduct a study which will involve: a) Synthesis of multifunctional therapeutic and osteoinductive calcium phosphate nanoparticles by means of co-precipitation from ultrasonically agitated emulsions;b) Drug release studies in bacterial and cell cultures. With respect to the proposed hypothesis, the central aim of this study is to derive fundamental correlations between the dissolution rate and drug delivery efficiency of calcium phosphate based carriers and their chemical composition and microstructure. This K99/R00 award is conceived to lead to an R01 grant, the writing of which will begin before the end of the award period.

Public Health Relevance

This research training program will enable the candidate, Dr. Vuk Uskokovic, to obtain expertise in cell culture experimentation and biological methods of characterization and testing, and thus complement his background in materials science and engineering of nanosized particles applicable for biomedical purposes. The material that will present the focus of Dr. Uskokovic's research will be clindamycin-containing calcium-phosphate/polymer composite, and he will be testing the hypothesis that the drug release rates could be controlled by varying stoichiometry and size of the calcium phosphate particles.
The research aim i s to build a time-tunable drug release carrier for the simultaneous prolonged antibiotic performance and regeneration of diseased hard tissues.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Career Transition Award (K99)
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NIDCR Special Grants Review Committee (DSR)
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Frieden, Leslie A
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University of California San Francisco
Schools of Dentistry
San Francisco
United States
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Uskokovi?, Vuk; Desai, Tejal A (2014) In vitro analysis of nanoparticulate hydroxyapatite/chitosan composites as potential drug delivery platforms for the sustained release of antibiotics in the treatment of osteomyelitis. J Pharm Sci 103:567-79
Uskokovi?, Vuk; Desai, Tejal A (2014) Does translational symmetry matter on the micro scale? Fibroblastic and osteoblastic interactions with the topographically distinct poly(?-caprolactone)/hydroxyapatite thin films. ACS Appl Mater Interfaces 6:13209-20
Uskokovi?, Vuk; Desai, Tejal A (2014) Simultaneous bactericidal and osteogenic effect of nanoparticulate calcium phosphate powders loaded with clindamycin on osteoblasts infected with Staphylococcus aureus. Mater Sci Eng C Mater Biol Appl 37:210-22
Stevanovi?, Magdalena; Uskokovi?, Vuk; Filipovi?, MiloŇ° et al. (2013) Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative, and antimicrobial activities. ACS Appl Mater Interfaces 5:9034-42
Uskokovi?, Vuk; Desai, Tejal A (2013) Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. I. Preparation and drug release. J Biomed Mater Res A 101:1416-26
Uskokovi?, Vuk (2013) Revisiting the Fundamentals in the Design and Control of Nanoparticulate Colloids in the Frame of Soft Chemistry. Rev J Chem 3:271-303
Ignjatovi?, Nenad; Ajdukovi?, Zorica; Savi?, Vojin et al. (2013) Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones. J Mater Sci Mater Med 24:343-54
Uskokovi?, Vuk (2013) Entering the era of nanoscience: time to be so small. J Biomed Nanotechnol 9:1441-70
Uskokovi?, Vuk; Hoover, Charles; Vukomanovi?, Marija et al. (2013) Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(D,L-lactide-co-glycolide) powders for the treatment of osteomyelitis. Mater Sci Eng C Mater Biol Appl 33:3362-73
Desai, Tejal A; Uskokovi?, Vuk (2013) Calcium phosphate nanoparticles: a future therapeutic platform for the treatment of osteomyelitis? Ther Deliv 4:643-5

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