Synthetic systems that provide structural support while activating endogenous cells to form functional bone tissues have been considered as an optimal therapeutic strategy for treating critical bone defects. Currently, autografts and allografs are the primary choice of implants, but both suffer from various drawbacks such as donor site morbidity, scarcity, immunorejection, or disease transmission. In contrast, synthetic bone grafts with intrinsic osteoinductivity and osteogenicity could provide an easy-to-manufacture, cost-effective, and widely available therapeutic strategy for treating bone defects/failures. In the proposed study, we will investigate the efficacy of a fully synthetic bone grafts being developed in our laboratory to form in vitro and in vivo bone tissues. The biomimetic bone graft described here is developed by using principles of biomineralization, which leads to formation of a synthetic bone-like extracellular matrix that recapitulates various static and dynamic physicochemical cues of the native tissue including the dynamic dissolution/formation of mineral phase. Using this graft, we will: (1) determine the role of various physicochemical cues from the matrix and the mineral environment on osteogenic differentiation of stem cells in vitro, (2) elucidate the mechanism by which the biomineralized grafts exhibits osteogenicity and osteoinductivity, and (3) in vivo bone formation ability of the grafts by using posterolateral fusin as a model system. The grafts are designed to provide the structural and mechanical integrity required for bone grafting, while activating endogenous cells to promote bone formation. Such an endogenous cell-driven strategy in regenerative medicine has the potential to circumvent the limitations of existing approaches associated with cost, space, and time. Such an approach involving synthetic grafts devoid of any growth factors will also confine the bone formation to the implant site and overcome major side effects associated with growth factor-containing grafts. Though the proposed study is focused on bone tissue formation and repair, the biomimetic approach can be applied to study other cells/systems, thus having a far-reaching impact.

Public Health Relevance

The proposal focuses on in vivo harnessing of osteoconductive and osteoinductive properties of a biomimetic synthetic bone grafts to direct osteogenic differentiation of progenitor cells and contribute to bone tissue repair. Successful completion of the proposed study will lead to development of an easy-to-manufacture, cost- effective bone repair strategy that could be a bona fide alternative to autografts. Additionally, this study will provide insights into the role of microenvironmental cues on pathological calcification enabling better drug developments for treating ectopic calcifications.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Musculoskeletal Tissue Engineering Study Section (MTE)
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Wang, Fei
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University of California San Diego
Engineering (All Types)
Schools of Arts and Sciences
La Jolla
United States
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Shih, Yu-Ru; Kang, Heemin; Rao, Vikram et al. (2017) In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism. Proc Natl Acad Sci U S A 114:5419-5424
Aung, Aereas; Theprungsirikul, Jomkuan; Lim, Han Liang et al. (2016) Chemotaxis-driven assembly of endothelial barrier in a tumor-on-a-chip platform. Lab Chip 16:1886-98
Wen, Cai; Kang, Heemin; Shih, Yu-Ru V et al. (2016) In vivo comparison of biomineralized scaffold-directed osteogenic differentiation of human embryonic and mesenchymal stem cells. Drug Deliv Transl Res 6:121-31
Aung, Aereas; Bhullar, Ivneet Singh; Theprungsirikul, Jomkuan et al. (2016) 3D cardiac ?tissues within a microfluidic device with real-time contractile stress readout. Lab Chip 16:153-62
Kang, Heemin; Shih, Yu-Ru V; Nakasaki, Manando et al. (2016) Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts. Sci Adv 2:e1600691
Seale, Nailah M; Varghese, Shyni (2016) Biomaterials for pluripotent stem cell engineering: From fate determination to vascularization. J Mater Chem B 4:3454-3463
Kar, Mrityunjoy; Vernon Shih, Yu-Ru; Velez, Daniel Ortiz et al. (2016) Poly(ethylene glycol) hydrogels with cell cleavable groups for autonomous cell delivery. Biomaterials 77:186-97
Shih, Yu-Ru; Phadke, Ameya; Yamaguchi, Tomonori et al. (2015) Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment. Acta Biomater 19:1-9
Rao, Vikram; Shih, Yu-Ru V; Kang, Heemin et al. (2015) Adenosine Signaling Mediates Osteogenic Differentiation of Human Embryonic Stem Cells on Mineralized Matrices. Front Bioeng Biotechnol 3:185
Davey, Shruti Krishna; Aung, Aereas; Agrawal, Gaurav et al. (2015) Embedded 3D Photopatterning of Hydrogels with Diverse and Complex Architectures for Tissue Engineering and Disease Models. Tissue Eng Part C Methods 21:1188-96

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