This proposal is multi-disciplinary and multi-institutional in nature and is one of the five components of a program submission on the rational design of the craniofacial complex from Pittsburgh researchers supported by the Pittsburgh Tissue Engineering Initiative. The present proposal has identified strategies to address a significant problem in craniofacial orthopedics and aims to determine a working range of parameters of biomechanical forces used to engineer osteogenesis in sutures and on periosteal surfaces of intramembranous bones. Improvement in understanding of engineering osteogenesis by biomechanical stimuli may provide a model of osteogenetic mechanisms different from those in long bones. Therefore, this application also targets one of NIAMS's interest areas of biomechanical induction of osteogenesis in intramembranous bones. The magnitude, mode and rate of in vivo bone strain will be quantified to determine what parameters can maximize craniofacial osteogenesis by means of bone strain measurements. Following chronic loading with selected force parameters, periosteal and sutural bone formation will be quantified by both atomic force microscopy and computer-assisted histomorphometric analysis with vital-stained bone specimens on the cortical bone surfaces and in craniofacial sutures. In vivo bone strain measurements will be quantified with a combined analysis of in vitro biomechanical properties of newly formed cortical and sutural bone tissues by atomic force microscopy. The proposed studies are anticipated not only to determine responses of craniofacial bones to selected parameters of biomechanical stimuli, but also to correlate mechanical stresses adjacent to craniofacial sutures with the amount of sutural bone formation, thus aiming to maximize both sutural and periosteal osteogenesis in craniofacial bones.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZDE1-YA (32))
Program Officer
Lumelsky, Nadya L
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Columbia University (N.Y.)
Schools of Dentistry
New York
United States
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Jiang, Nan; Guo, Weihua; Chen, Mo et al. (2016) Periodontal Ligament and Alveolar Bone in Health and Adaptation: Tooth Movement. Front Oral Biol 18:1-8
Sun, Guoming; Mao, Jeremy J (2012) Engineering dextran-based scaffolds for drug delivery and tissue repair. Nanomedicine (Lond) 7:1771-84
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Moioli, Eduardo K; Clark, Paul A; Sumner, D Rick et al. (2008) Autologous stem cell regeneration in craniosynostosis. Bone 42:332-40
Othman, Hasan; Thonar, Eugene J; Mao, Jeremy J (2007) Modulation of neonatal growth plate development by ex vivo intermittent mechanical stress. J Biomech 40:2686-93
Stosich, Michael S; Mao, Jeremy J (2007) Adipose tissue engineering from human adult stem cells: clinical implications in plastic and reconstructive surgery. Plast Reconstr Surg 119:71-83;discussion 84-5
Moioli, Eduardo K; Clark, Paul A; Xin, Xuejun et al. (2007) Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering. Adv Drug Deliv Rev 59:308-24
Sundaramurthy, Sona; Mao, Jeremy J (2006) Modulation of endochondral development of the distal femoral condyle by mechanical loading. J Orthop Res 24:229-41

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