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Making Materials for the Future W. M. Keck Biomedical Materials Research Lab

Activities

The following briefly outlines our activities in key research areas.

Materials and structures for next generation load bearing implants

Musculoskeletal disorders are recognized as among the most significant human health problems that exist today, afflicting one out of seven Americans. In spite of enormous magnitude of this problem, there is still a lack of bone replacement material that is appropriate for restoring lost structure and function, particularly for load bearing applications. A typical example is total hip replacements (THR) in which a dense metal is used with significantly higher density, stiffness and strength than natural bone, which is a porous material. Typical lifetime of a THR is between seven to twelve years and this lifetime has remained almost constant over the past fifty years, even though significant research and development has gone towards understanding the problem. First major problem concerning metallic implants is the mismatch of Young’s modulus between bone (10–30 GPa) and metallic materials (110 GPa for Ti and 210 GPa for Co-Cr-Mo). The second problem with metallic implants lies in the interfacial bond between the tissue and the implant due to bio-inert nature of metals. Our hypothesis is that use of porous materials in implants can reduce the stiffness mismatches due to porosity and achieve stable long-term biological fixation due to bone-tissue in-growth into interconnected porosity from the surface to the inside. However, the influence of both open and closed porosity in properties of metallic implants particularly physical such as density, mechanical such as compressive strength and modulus and biological such as bone tissue in growth and mineralization are still unknown. Our activities are focused on development of new materials and structures for next generation of load bearing materials using novel processing science and characterization tools. Funding for this research is coming from the W. M. Keck Foundation, the National Science Foundation, the Office of Naval Research and the M. J. Murdock Charitable Trust.

Nanoscalse resorbable ceramics in tissue engineering and drug delivery

Calcium phosphate (CaP) based ceramics are used in hard tissue engineering because of their excellent biocompatibility. There is a need for the development of biodegradable ceramic materials with controlled degradation kinetics that will act as a scaffold and support bone remodeling. Our aim is to elucidate strength loss mechanism in CaP based material and scaffold to develop bone graft for specific application. Fundamental information on controlled degradation behavior of CaP based materials to identify optimal material composition can help us design and tailor resorbable tissue engineered bone replacement based on application needs. The objective of this research is to test our hypothesis, which is chemistry and microstructure in CaP based ceramics can modify strength loss in these materials. Our preliminary data indicate that a minimum amount of trace elements (dopants) can have significant effects on physical and mechanical properties of CaPs. Cell-materials interactions can also be influenced by the presence of trace elements. We are conducting a series of studies including synthesis of nanoscale CaPs with single and multi element dopants, characterize their chemical, physical and mechanical properties, and in vitro and in vivo strength loss behavior in rat and rabbit models. We envision that this study will lead to the development of CaPs with tailored degradation kinetics that can be used in spinal fusion, maxillo- and cranio-facial implants and small scale bone defect applications. Funding for this research is coming from the National Institute of Health, the National Science Foundation, the M. J. Murdock Charitable Trust, the W. M. Keck Foundation, the Office of Naval Research.

Surface modification for improving cell materials interactions

Metals are used extensively in load bearing implants. Among various metals, Ti is probably the most widely used for dental and orthopedic implants due to low toxicity, superior corrosion resistance, favorable mechanical properties and good biocompatibility. Since Ti is a bioinert material, biomedical devices made of Ti gets encapsulated after implantation into the living body by fibrous tissue that isolates them from the surrounding tissues. Release of Ti ions from the implant remains another concern. Our research is focused on improving biocompatibility of Ti and its alloys via surface modification. Our hypothesis is that surface modified Ti will show faster osseointegration and reduce healing time in vivo. Our research is focused on two different approaches to cell materials interactions via surface modification – (1) growing in situ oxide layer on Ti and (2) depositing a functionally and compositionally gradient coating on Ti, and studying the influence of surface properties on mechanical and biological responses. Infection is another factor often associated with surgery. Infections may even cause removal of prosthesis or significant delay in healing. This is often due to the accumulation of microbial plaque or biofilm on implants, screws or plates, which contribute to recurrent infections as well as causing bone loss or prevention of bone deposition that ultimately is required to anchor the implant. Our surface modification research is also focused on understanding the influence of surface modification on antimicrobial activities to reduce post surgical infections. Funding for this research is coming from the National Institute of Health, Office of Naval Research and the W. M. Keck Foundation.

Micromachined ultrasonic transducers in biomedical imaging and therapeutics

The flexibility and non-invasive nature of ultrasonic imaging compared to other medical diagnosis techniques has made it an important diagnostic tool in medicine since early 70’s. Some of its most popular applications include routine pregnancy scans and heart scans (echocardiograms). Until recently, ultrasound system typically used a one dimensional linear array of transducers to focus the acoustic beam into a tomographic plane to obtain two dimensional (2D) images on these planes. In 2D imaging, many critical questions are often left out for speculation as a result of 2D cross-sectional representation of a 3D volume. More recent development of ultrasound imaging system has been focused on the 3D imaging using two dimensional arrays of transducers. The development has led to the commercialization of some two dimensional ultrasound probes. Current commercial 2D transducer probes that costs >20x higher than a typical current transducer product are also limited to arrays with element pitch of 200 to 300 microns and operating frequencies of <5MHz. The significant barriers for further development are the complexity, cost of manufacturing, and limited performance of these systems. Moreover, forward looking 2D array transducer for catheter based imaging probes has not yet been achieved commercially in which the transducer array should be less than 2 mm in diameter. Our group has been involved with first generation research on MEMS-based piezoelectric micromachined ultrasonic transducers (pMUTs) for the past eight years that can offer solutions to the problems in the areas of 3D medical ultrasonic imaging. pMUT, is a micromachined multilayered membrane resonator, typically in the order of 10’s of micrometers, which can be used as sound radiating element in biomedical imaging and therapeutics. Funding for this research is coming from the Office of Naval Research.