Laser Sintered Porous Ti–6Al–4V Implants Stimulate Vertical Bone Growth ALICE CHENG, 1,2 DAVID J. COHEN, 3 ADRIAN KAHN, 4 RYAN M. CLOHESSY, 3 KAAN SAHINGUR, 3 JOSEPH B. NEWTON, 3 SHARON L. HYZY, 3 BARBARA D. BOYAN, 1,3,6 and ZVI SCHWARTZ 3,5 1 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA; 2 Department of Biomedical Engineering, Peking University, Beijing, China; 3 Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA; 4 Department of Oral Surgery, University of Tel-Aviv, Tel Aviv, Israel; 5 Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; and 6 School of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, USA (Received 15 January 2017; accepted 4 April 2017) Associate Editor Sean S. Kohles oversaw the review of this article. Abstract—The objective of this study was to examine the ability of 3D implants with trabecular-bone-inspired poros- ity and micro-/nano-rough surfaces to enhance vertical bone ingrowth. Porous Ti–6Al–4V constructs were fabricated via laser-sintering and processed to obtain micro-/nano-rough surfaces. Male and female human osteoblasts were seeded on constructs to analyze cell morphology and response. Im- plants were then placed on rat calvaria for 10 weeks to assess vertical bone ingrowth, mechanical stability and osseointe- gration. All osteoblasts showed higher levels of osteocalcin, osteoprotegerin, vascular endothelial growth factor and bone morphogenetic protein 2 on porous constructs compared to solid laser-sintered controls. Porous implants placed in vivo resulted in an average of 3.1 ± 0.6 mm 3 vertical bone growth and osseointegration within implant pores and had signifi- cantly higher pull-out strength values than solid implants. New bone formation and pull-out strength was not improved with the addition of demineralized bone matrix putty. Scanning electron images and histological results corrobo- rated vertical bone growth. This study indicates that Ti–6Al– 4V implants fabricated by additive manufacturing to have porosity based on trabecular bone and post-build processing to have micro-/nano-surface roughness can support vertical bone growth in vivo, and suggests that these implants may be used clinically to increase osseointegration in challenging patient cases. Keywords—Biomaterials, Gender differences, Guided tissue regeneration, Osteoblasts, Osseointegration, Surface proper- ties. INTRODUCTION Dental implant success remains a challenge for compromised patients such as the elderly, smokers, diabetics and patients undergoing irradiation therapy of the head and neck. 17 Implants with porosity are now being introduced as a way to enhance bone formation in compromised patients. 2 Histological studies in the rabbit have also indicated blood vessel formation in concavities of implants, suggesting that porosity may also enhance vascularization. 21 Titanium and its alloys are still the preferred materials for bone interfacing implants based on their ability to osseointegrate, as well as their corrosion resistance and mechanical properties. 8,11 Although tantalum-coated porous implants have been intro- duced into the market, they have shown only compa- rable but not superior performance to solid implants. 15 In addition, these and other porous implants made using traditional manufacturing techniques cannot be manufactured in one piece, requiring additional pro- cessing. Selective laser sintering (SLS) is a form of additive manufacturing that is able to create high resolution, patient-specific titanium–aluminum–vanadium (Ti– 6Al–4V) constructs and bone-interfacing implants in one step. By increasing porosity, compressive moduli of the constructs decreased to better mimic the natural modulus of bone. 5 Previous studies have shown that human osteoblasts exhibit higher expression of factors favoring osteoblastic differentiation and maturation, including osteocalcin, vascular endothelial growth factor (VEGF) and bone morphogenetic proteins Address correspondence to Barbara D. Boyan, School of Engi- neering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, USA. Electronic mail: bboyan@vcu.edu Alice Cheng and David J. Cohen contributed equally to this work. Annals of Biomedical Engineering (Ó 2017) DOI: 10.1007/s10439-017-1831-7 Ó 2017 Biomedical Engineering Society