Non-Technical: This award by the Biomaterials Program in the Division of Materials Research to Stevens Institute of Technology is to develop human tissue-like materials that could be used in place of animal testing for drug evaluation. The regulation of osteoblasts by osteocytes for new bone formation is a major target for development of new drugs for treating 10 million osteoporosis patients, and cancer patients with bone metastases which result in 350,000 deaths every year in the U.S. For these diseases, this project will provide a more clinically relevant method of evaluating drugs than animal testing, as the latter is known to poorly predict drug response in humans. This study will, therefore, offer an important new insight in addressing pharmaceutical industry's need to lower the number of costly drug failures that occur during clinical trials. With regard to broader impacts, this project will bring the excitement of discovery, collaboration, and entrepreneurship to: 1) graduate students through interdisciplinary activities; 2) undergraduate students via summer research experiences; and 3) high school students through the American Chemical Society's Summer Research Internship Program for Economically Disadvantaged High School Students. Students will be challenged to develop business plans that can translate discoveries to entrepreneurial opportunities at levels appropriate for their educational stages. This innovation theme is important in our geographical area where biomedical research plays a key role in propelling the regional, national, and global economies.
With this award, the investigators will reconstruct in vitro the 3-dimensional (3D) lacunocanalicular network structure of cortical human bones. In order to mimic the network's multi-scale 3D geometrical features, a biomimetic approach will be used to hierarchically assemble microbeads and nanoparticles with primary osteocyte cells harvested from human bones within a microfluidic perfusion culture chamber. The biomimetic approach will enable: (1) long-term culture of primary human osteocytes which has not been possible to date; and (2) ex vivo investigation of biomaterial effects on the cellular response of osteocytes for the first time. The specific objectives of the project are to: (1) investigate the effects of biphasic calcium phosphate and hydroxyapatite nanoparticles on extracellular matrix production by human primary osteocytes and remodeling of their lacunocanalicular space; and (2) reproduce the physiological role of the reconstructed osteocyte network in incorporating neighboring osteoblasts into the cellular network and regulating the spatiotemporal transition of the osteoblasts to osteocytes, as mechanisms by which new bone tissue is formed during homeostatic bone remodeling.
