This award by the Biomaterials program in the Division of Materials Research to Stevens Institute of Technology is to explore the inkjet printing of drug-eluting, bioresorbable micropatterns onto the surface of orthopaedic implants, as a novel means of preventing bacterial infection of the implants. Infection occurs because a small number of bacteria adhere preferentially to abiotic implant surfaces and form biofilms, in which the bacteria are protected from host defense and antibiotics. The project seeks to establish a new paradigm by which future implant surfaces are engineered to prevent bacteria attachment and biofilm formation and, at the same time, to promote their osteointegration function. This research is important and timely, since hospital-acquired bacterial infection during implantation procedures has emerged as the dominant mode of implant failure. During inkjet printing, evaporative assembly mechanisms are used to create nanocomposite micropatterns which consist of calcium phosphate and antibiotic nanocrystals (~100 nm) dispersed in a biodegradable polymer matrix. Inks are formulated to tailor nanocomposite morphology for: 1) steady antibiotic release as a mechanism of killing opportunistic bacteria that will come in contact with implant surfaces and thus preventing biofilm formation; and 2) optimization of the osteoconductive property of calcium phosphate nanocrystals for rapid and direct new bone formation. Microfluidic co-culture tools are used to project the ability of micropatterns to prevent biofilm formation while enhancing the formation of 3D bone tissue-like structures on the titanium alloy surface. Results from this project are used to define the criteria for designing implant surfaces for optimum infection-prevention and wound-healing functions. The project also supports the interdisciplinary training of one doctoral and twelve undergraduate students with the excitement of discovery, collaboration, and entrepreneurship in developing a new generation of infection-preventing biomedical devices.
This project explores the inkjet printing of drug-eluting, bioresorbable micropatterns onto the surface of orthopaedic implants, as a novel means of preventing bacterial infection of the implants. While our ability to produce orthopaedic implants has tremendously improved over past several decades, hospital-acquired bacterial infection during implantation procedures has emerged as the dominant mode of implant failure. Infection occurs because a small number of bacteria adhere preferentially to implant surfaces and form biofilms, which protect the bacteria from host defense and antibiotics. Consequently, infected implants must be surgically removed with tremendous patient trauma and additional healthcare burden of over $3B in the U.S. every year. Despite the severity of this infection problem, progress has been limited due to the lack of our understanding of the complex interplay among host tissues, bacteria, and biomaterials. This research seeks to provide a new scientific understanding for designing infection-preventing implant by establishing a highly cross-disciplinary research frontier that cuts across biomaterials, device infection, and microfluidics. The inkjet-printed micropattern concept, as an example of this new paradigm, offers a transformative solution to the infection problem by eliminating the formation of biofilm by bacteria while promoting rapid and strong bone formation on the implant surfaces. The project also supports the interdisciplinary training of one doctoral and twelve undergraduate students with the excitement of discovery, collaboration, and entrepreneurship in developing a new generation of infection-preventing biomedical devices. This theme is extremely important to the Northern New Jersey area, where the biomedical device industry plays a key role in the regional, national, and global economies.
The goal of this project was to explore the possibility of creating drug-eluting, bioresorbable micropatterns that can be used to promote bone tissue formation and prevent biofilm formation on orthopaedic implant surfaces. The key methodology was to use a microfluidic 3-dimensional bone tissue mode to evaluate the efficacy of infection-preventing biomaterials. As illustrated in the attached images, we demonstrated: (1) the drug-eluting functions of inkjet-printed micropatterns with antibiotic- and calcium-containing nanoparticles dispersed in a bioresorbable polymer matrix and (2) the micropatterns’ efficacy in immediately and completely killing bacteria while enhancing the calcified extracellular matrix production of bone forming cells. These findings strongly suggested that the micropatterning concept is promising as a new approach for preventing bacterial infection associated with orthopaedic implants while accelerating wound healing via new bone formation. These findings are important since hospital-acquired bacterial infection during implant surgery is the leading cause of orthopaedic implant failure with tremendous patient trauma and additional healthcare burden of >$1B in the U.S. every year. This project provided: (1) interdisciplinary training to four doctoral students including three females, (2) research experiences to three undergraduate students including two female students and a winner of the prestigious Barry Goldwater Scholarship, and (3) four high school students including two from economically disadvantaged minority backgrounds.
