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Laser-Sintered Constructs with Bio-inspired Porosity and Surface Micro/Nano-Roughness Enhance Mesenchymal Stem Cell Differentiation and Matrix Mineralization In Vitro

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Abstract

Direct metal laser sintering can produce porous Ti–6Al–4V orthopedic and dental implants. The process requires reduced resources and time and can provide greater structural control than machine manufacturing. Implants in bone are colonized by mesenchymal stem cells (MSCs), which can differentiate into osteoblasts and contribute to osseointegration. This study examined osteoblast differentiation and matrix mineralization of human MSCs cultured on laser-sintered Ti–6Al–4V constructs with varying porosity and at different time scales. 2D solid disks and low, medium and high porosity (LP, MP, and HP) 3D constructs based on a human trabecular bone template were laser sintered from Ti–6Al–4V powder and further processed to have micro- and nanoscale roughness. hMSCs exhibited greater osteoblastic differentiation and local factor production on all 3D porous constructs compared to 2D surfaces, which was sustained for 9 days without use of exogenous factors. hMSCs cultured for 8 weeks on MP constructs in osteogenic medium (OM), OM supplemented with BMP2 or collagen-coated MP constructs in OM exhibited bone-like extracellular matrix mineralization. Use of bio-inspired porosity for the 3D architecture of additively manufactured Ti–6Al–4V enhanced osteogenic differentiation of hMSCs beyond surface roughness alone. This study suggests that a 3D architecture may enhance the osseointegration of orthopedic and dental implants in vivo.

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Acknowledgments

The authors would like to thank Aiza Humayan for assistance with cell culture. AB Dental (Ashdod, Israel) generously donated the implants and substrates used in this study. Research reported in this publication was supported by AB Dental and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number AR052102. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive NW, Atlanta, GA, 30313, USA

    Alice Cheng & Barbara D. Boyan

  2. Department of Biomedical Engineering, Peking University, Peking University Hospital Building A503, Haidian District, Beijing, 100871, China

    Alice Cheng

  3. Department of Biomedical Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA, 23284, USA

    David J. Cohen, Barbara D. Boyan & Zvi Schwartz

  4. Department of Periodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Zvi Schwartz

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  1. Alice Cheng
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Correspondence to Barbara D. Boyan.

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Conflict of Interest

BDB is an paid consultant for Titan Spine LLC and an unpaid consultant for Institut Straumann AG. ZS is a paid consultant for AB Dental. AC and DJC declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All animal procedures were performed in compliance with the 1991 Guiding Principles in the Care and Use of Animals, approved by the Council of the American Physiological Society. No human subjects used in this study.

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Cheng, A., Cohen, D.J., Boyan, B.D. et al. Laser-Sintered Constructs with Bio-inspired Porosity and Surface Micro/Nano-Roughness Enhance Mesenchymal Stem Cell Differentiation and Matrix Mineralization In Vitro. Calcif Tissue Int 99, 625–637 (2016). https://doi.org/10.1007/s00223-016-0184-9

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  • DOI: https://doi.org/10.1007/s00223-016-0184-9

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