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Three-Dimensional Nano-Architected Scaffolds with Tunable Stiffness for Efficient Bone Tissue Growth

Maggi, Alessandro and Li, Hanqing and Greer, Julia R. (2017) Three-Dimensional Nano-Architected Scaffolds with Tunable Stiffness for Efficient Bone Tissue Growth. Acta Biomaterialia, 63 . pp. 294-305. ISSN 1742-7061. PMCID PMC5663471. doi:10.1016/j.actbio.2017.09.007.

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The precise mechanisms that lead to orthopedic implant failure are not well understood; it is believed that the micromechanical environment at the bone-implant interface regulates structural stability of an implant. In this work, we seek to understand how the 3D mechanical environment of an implant affects bone formation during early osteointegration. We employed two-photon lithography (TPL) direct laser writing to fabricate 3-dimensional rigid polymer scaffolds with tetrakaidecahedral periodic geometry, herewith referred to as nanolattices, whose strut dimensions were on the same order as osteoblasts’ focal adhesions (∼2μm) and pore sizes on the order of cell size, ∼10μm. Some of these nanolattices were subsequently coated with thin conformal layers of Ti or W, and a final outer layer of 18nm-thick TiO_2 was deposited on all samples to ensure biocompatibility. Nanomechanical experiments on each type of nanolattice revealed the range of stiffnesses of 0.7-100 MPa. Osteoblast-like cells (SAOS-2) were seeded on each nanolattice, and their mechanosensitve response was explored by tracking mineral secretions and intracellular f-actin and vinculin concentrations after 2, 8 and 12 days of cell culture in mineralization media. Experiments revealed that the most compliant nanolattices had ∼20% more intracellular f-actin and ∼40% more Ca and P secreted onto them than the stiffer nanolattices, where such cellular response was virtually indistinguishable. We constructed a simple phenomenological model that appears to capture the observed relation between scaffold stiffness and f-actin concentration. This model predicts a range of optimal scaffold stiffnesses for maximum f-actin concentration, which appears to be directly correlated with osteoblast-driven mineral deposition. This work suggests that three-dimensional scaffolds with titania-coated surfaces may provide an optimal microenvironment for cell growth when their stiffness is similar to that of cartilage (∼0.5-3MPa). These findings help provide a greater understanding of osteoblast mechanosensitivity and may have profound implications in developing more effective and safer bone prostheses. Statement of Significance: Creating prostheses that lead to optimal bone remodeling has been a challenge for more than two decades because of a lack of thorough knowledge of cell behavior in three-dimensional (3D) environments. Literature has shown that 2D substrate stiffness plays a significant role in determining cell behavior, however, limitations in fabrication techniques and difficulties in characterizing cell-scaffold interactions have limited our understanding of how 3D scaffolds’ stiffness affects cell response. The present study shows that scaffold structural stiffness affects osteoblasts cellular response. Specifically this work shows that the cells grown on the most compliant nanolattices with a stiffness of 0.7MPa expressed ∼20% higher concentration of intracellular f-actin and secreted ∼40% more Ca and P compared with all other nanolattices. This suggests that bone scaffolds with a stiffness close to that of cartilage may serve as optimal 3D scaffolds for new synthetic bone graft materials.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Maggi, Alessandro0000-0001-9438-7258
Greer, Julia R.0000-0002-9675-1508
Additional Information:© 2017 Acta Materialia Inc. Published by Elsevier Ltd. Received 16 June 2017, Revised 19 August 2017, Accepted 7 September 2017, Available online 18 September 2017. JRG and AM gratefully acknowledge the financial support of Amgen through AM’s graduate fellowship.
Funding AgencyGrant Number
Subject Keywords:Two-photon lithography; Scaffold; Micro fabrication; Mechanical characterization; Mineralization; Mechanics
PubMed Central ID:PMC5663471
Record Number:CaltechAUTHORS:20170919-085010063
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Official Citation:Alessandro Maggi, Hanqing Li, Julia R. Greer, Three-dimensional nano-architected scaffolds with tunable stiffness for efficient bone tissue growth, In Acta Biomaterialia, Volume 63, 2017, Pages 294-305, ISSN 1742-7061,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:81557
Deposited By: Tony Diaz
Deposited On:19 Sep 2017 16:12
Last Modified:22 Mar 2022 19:20

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