Nanoroughened Microstructured Orthopaedic Implant Surfaces Support Production of Factors that Induce Ectopic Osteogenesis in a Preclinical Osteoinduction Model — The International Society for the Study of the Lumbar Spine
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Nanoroughened Microstructured Orthopaedic Implant Surfaces Support Production of Factors that Induce Ectopic Osteogenesis in a Preclinical Osteoinduction Model (#1030)

Michael B Berger 1 , David J Cohen 1 , Michael L Levit 1 , Kyla B Bosh 1 , Marina Kapitanov 1 , Michelle B Gallagher 2 , Paul J Slosar 3 , Zvi Schwartz 1 4 , Barbara D Boyan 1 5
  1. Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA
  2. Medtronic Spine, Mequon, WI, USA
  3. San Francisco Spine Institute, San Francisco, CA, USA
  4. Periodontology , University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
  5. Biomedical Engineering, Georgia Institute of Technology, Atlanta , GA, USA

Introduction: There is a growing clinical need to create implants with material properties that promote accelerated osseointegration and reduced recovery time in compromised bone. We have shown that machined Ti-based implants possessing biomimetic surface topographies can direct osteoblast differentiation of multipotent bone marrow stromal cells (MSCs) in vitro and improve osseointegration in vivo in both animals and humans and that this process occurs through paracrine signaling and increased local factor production. This study examined the hypothesis that MSCs grown on nanotextured microstructured Ti6Al4V surfaces produce factors that support osteoinduction in vivo.

Methods: Ti6Al4V disks were grit-blasted and acid-etched, producing complex topography at the macro/micro/nanoscale (MMN; Medtronic). All cultures were grown on tissue culture polystyrene (TCPS) or MMN surfaces in MSC growth media (GM) absent of osteogenic growth media supplements.

Study 1: Athymic mice were divided into 4 groups: active demineralized bone matrix (aDBM) (LifeNet Health, Virginia Beach, VA), heat inactivated DBM (iDBM), iDBM+GM (fresh media), and iDBM+TCPS-CM proteins. TCPS-conditioned media was derived by culturing MSCs on TCPS surfaces for 14d and lyophilizing the conditioned media (CM). Gel capsules were implanted bilaterally into intramuscular pockets created in the hind limbs (N=8 capsules/group). Legs were harvested at D35. Mineralization was assessed by micro-CT.

            Study 2: Athymic mice were divided into 3 groups: iDBM, iDBM+rhBMP2 (R&D Systems) at a concentration similar to in vitro production of MSCs on MMN surfaces (MMN-CM concentration), and iDBM+MMN-CM proteins. MMN-CM was derived by culturing MSCs on MMN surfaces for 10d and lyophilizing the CM from D5-D10 to capture proteins produced after responding to surface properties and during differentiation/maturation. Gel capsules were implanted bilaterally into intramuscular pockets created in the hind limbs (N=8 capsules/group). Legs were harvested at 35D. Bone formation was assessed by micro-CT and histomorphometry (H&E Staining). Histology was scored according to ASTM 2529-13.  

Results: Micro-CT demonstrated robust ectopic bone formation in the aDBM group. iDBM, iDBM+GM, and iDBM+TCPS-CM demonstrated significantly little ectopic mineralization. In study 2, micro-CT revealed greater mineralized tissue in iDBM+MMN-CM groups compared to iDBM and iDBM+BMP2. Additionally, there was more live bone in the MMN-CM group compared to iDBM as quantified by quantitative histomorphometry. Scoring of histology slides according to ASTM 2529-13 demonstrated an average scoring rank of 3.125 (passing) for MMN-CM explants and a failing scoring rank of 1.375 for iDBM.

Conclusions: MSCs cultured on nanoroughened microtextured Ti6Al4V surfaces differentiate and produce local factors that can induce ectopic bone formation through a combination of paracrine signaling factors in addition to BMP2. Proteins comprising fresh GM, or TCPS-CM do not possess capabilities of increased osteogenesis in a mouse model. Nanotextured microstructured biomimetic surfaces induce local factor production, which increased bone formation in a mouse model compared to iDBM and iDBM+BMP2 treatment groups. This indicates that the surface topography has an osteoinductive effect via surface-dependent osteogenic differentiation of the MSCs, potentially supporting better osseointegration and may provide an alternative to expensive pharmacologic agents like rhBMP2 during implant placement in patients with compromised bone quality.

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