Musculoskeletal diseases affect approximately 110 million adults in the United States, and metallic orthopedic implants are widely used to treat these conditions. However, failure of osseointegration and implant- related infections significantly reduce the long-term success of the implants. Current management strategies focus on implant modifications to promote osteogenic property or introduce antimicrobial function. However, none of these modifications can simultaneously address both issues and it is particularly difficult to enhance osseointegration while controlling peri-operative and/or post-operative infections/reinfections caused by bacteria from biofilms formed on the implant surface or pathogen-invaded osteoblasts. This project will use chitosan-based polycationic surface modifications to enhance osteogenic activity of osteoblast, activate the antibiotic susceptibility f bacteria, and prevent invasion of bacteria into osteoblasts. We have demonstrated that treating titanium with sulfuric acid (H2SO4) creates a roughened/porous surface that significantly improve osteogenic activity. Unfortunately, a rough surfaces can also promote bacterial aggregation, leading to implant-related infections and/or device failure. However, after we covalently bonded chitosan onto the H2SO4-treated surface, the resulting chitosan-bonded rough surface showed greatly enhanced osteogenic activity of cells, completely prevented invasion of bacteria into the pre-attached osteoblasts, and significantly activated the antibiotic susceptibility of adherent bacteria. Building on these pilot results, in this proposed project we wll further develop the new technology by establishing optimal surface- modification techniques for maximizing the osteogenic/bacteria-resistant performance of the materials. To achieve this, the specific aims of the proposed research are to (1) fabricate new chitosan-based titanium surfaces with a wide range of polycation levels, and evaluate the physical/mechanical properties of the new materials. Polycation levels will be controlled by the content of surface-bonded chitosan, post-acetylation (to reduce cation level) and post-quaternization (to increase cation level) of the bonded chitosan;and (2) evaluate in vitro the bacteria-resistant and osteogenic performance of the new materials. Osteogenic and bacteria- resistant performance will be tested at each polycation level. The 5 samples with the best overall performance will be further evaluated in two bacteria-osteoblast co-culture models. If found to be feasible and efficacious in this R21 study, the new osteogenic and bacteria-resistant technology can significantly improve the quality of orthopedic devices through promoting bony cell growth at the tissue-prosthetic device interfaces and controlling implant-associated infection. This improvement will benefit millions of patients. In addition, the new technology can be used with a broad range of other implantable medical devices to improve the long-term success of the implants, making an even greater positive impact on health.

Public Health Relevance

Implant-related infections and failure of osseointegration are significant clinical challenges of orthopedic devices. This project aims to develop new prosthetic device materials that simultaneously resist bacterial infection and promote bone growth. The new technology can potentially lead to the next generation orthopedic device materials to significantly improve the long-term success of prosthetic implants, and may also be needed to develop a broad range of other implant materials to improve tissue integration and reduce the risk of device- related infections, making an even greater positive impact on public health.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Grants (R21)
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Musculoskeletal Tissue Engineering Study Section (MTE)
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Panagis, James S
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University of Massachusetts Lowell
Schools of Arts and Sciences
United States
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Ghimire, Niranjan; Foss, Berit L; Sun, Yuyu et al. (2016) Interactions among osteoblastic cells, Staphylococcus aureus, and chitosan-immobilized titanium implants in a postoperative coculture system: An in vitro study. J Biomed Mater Res A 104:586-594
Foss, Berit L; Ghimire, Niranjan; Tang, Ruogu et al. (2015) Bacteria and osteoblast adhesion to chitosan immobilized titanium surface: A race for the surface. Colloids Surf B Biointerfaces 134:370-6
Ghimire, Niranjan; Luo, Jie; Tang, Ruogu et al. (2014) Novel anti-infective activities of chitosan immobilized titanium surface with enhanced osteogenic properties. Colloids Surf B Biointerfaces 122:126-133