ORIGINAL RESEARCH Laser-Sintered Constructs with Bio-inspired Porosity and Surface Micro/Nano-Roughness Enhance Mesenchymal Stem Cell Differentiation and Matrix Mineralization In Vitro Alice Cheng 1,2 • David J. Cohen 3 • Barbara D. Boyan 1,3 • Zvi Schwartz 3,4 Received: 16 June 2016 / Accepted: 28 July 2016 Ó Springer Science+Business Media New York 2016 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 con- tribute 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 pro- cessed 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. Keywords Additive manufacturing Á Stem cells Á Bone regeneration Á Orthopedic implants Á Dental implants Introduction Additive manufacturing of metals, the industrial term for ‘‘3D printing,’’ has been credited with huge potential for the future of orthopedic and dental implants; implants can be customized and fabricated to be porous for mechanical and biological fixation. The use of additive manufacturing to develop materials with non-traditional architecture can reduce material waste with potential financial savings [1, 2]. Large animal studies point toward the success of these implants for clinical use [3, 4]. A recent study by researchers in Italy showed a 97.4 % 3-year implant clinical survival rate for direct metal laser-sintered dental implants used to support maxillary overdentures, the first long-term clinical study of its kind [5]. Varying porosity of three-dimensional (3D) implants also offers the ability to increase surface area for bone-to-implant contact, promote blood vessel formation and tailor a mechanical modulus that more closely mimics bone than conventional solid implants [6–9]. Our laboratory previously manufactured 3D titanium– aluminum–vanadium (Ti–6Al–4V) constructs with Electronic supplementary material The online version of this article (doi:10.1007/s00223-016-0184-9) contains supplementary material, which is available to authorized users. & Barbara D. Boyan bboyan@vcu.edu 1 Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive NW, Atlanta, GA 30313, USA 2 Department of Biomedical Engineering, Peking University, Peking University Hospital Building A503, Haidian District, Beijing 100871, China 3 Department of Biomedical Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, USA 4 Department of Periodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA 123 Calcif Tissue Int DOI 10.1007/s00223-016-0184-9