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Modular peptides promote human mesenchymal stem cell differentiation on biomaterial surfaces
Authors:Jae Sam Lee  Jae Sung Lee  William L. Murphy
Affiliation:1. Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA;2. Department of Pharmacology, University of Wisconsin-Madison, Madison, WI 53706, USA;3. Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA;1. The G. W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA;2. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA;3. School of Biology, Georgia Institute of Technology, Atlanta, GA, USA;4. The Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA;5. School of Engineering, Virginia Commonwealth University, Richmond, VA, USA;1. Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona, Spain;2. Centre for Research in NanoEngineering (CRNE) – UPC, C/Pascual i Vila 15, 08028 Barcelona, Spain;3. Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330–714, Republic of Korea;4. Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330–714, Republic of Korea;5. Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330–714, Republic of Korea;6. Institute for Bioengineering of Catalonia (IBEC), C/Baldiri Reixac 10, 08028 Barcelona, Spain;3. From the Nagahama Institute for Biochemical Science and;4. Biochemical Production and Development Center, Oriental Yeast Co., Ltd., 50 Kano-cho Nagahama, Shiga 526-0804, Japan,;12. the Bioindustry Division, Oriental Yeast Co., Ltd., 3-6-10 Azusawa, Itabashi-ku, Tokyo 174-8505, Japan,;5. Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan,;6. the Institute of Molecular Biotechnology, Austrian Academy of Sciences, A-1030 Vienna, Austria, and;1. Division of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong, People''s Republic of China;2. Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong, People''s Republic of China;3. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People''s Republic of China;4. Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong, People''s Republic of China;1. Center for Biomaterials, Korea Institute of Science & Technology, Seoul, 130-650, Republic of Korea;2. Department of Biomolecular Science, University of Science and Technology (UST), Seoul, 136-791, Republic of Korea;3. Department of Pharmacology and Dental Therapeutics, and Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea;1. Department of Orthopaedic Surgery, National University of Singapore, Kent Ridge, Singapore 119074, Singapore;2. School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
Abstract:Molecular design strategies in biomedical applications often involve creating modular “fusion” proteins, in which distinct domains within a single molecule can perform multiple functions. We have synthesized a new class of modular peptides that include a biologically active sequence derived from the growth factor BMP-2 and a series of hydroxyapatite-binding sequences inspired by the N-terminal α-helix of osteocalcin. These modular peptides can bind in a sequence-dependent manner to the surface of “bone-like” hydroxyapatite coatings, which are nucleated and grown on a biodegradable polymer surface via a biomimetic process. The BMP-2-derived sequence of the modular peptides is biologically active, as measured by its ability to promote osteogenic differentiation of human mesenchymal stem cells. Our study indicates that the modular peptides described here are multifunctional, and the characteristics of this approach suggest that it can potentially be applied to a range of biomaterials for regenerative medicine applications.
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