Abstract

Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response. Here, we present a surface engineering method of translating bioactive nanopatterns from polymeric in vitro studies to clinically relevant material for orthopedics: three-dimensional, large area metal. We use a titanium-based sol–gel whereby metal implants can be engineered to induce osteoinduction both in vitro and in vivo. We show that controlled disordered nanotopographies presented as pillars with 15–25 nm height and 100 nm diameter on titanium dioxide effectively induce osteogenesis when seeded with STRO-1-enriched human skeletal stem cells in vivo subcutaneous implantation in mice. After 28 days, samples were retrieved, which showed a 20-fold increase in osteogenic gene induction of nanopatterned substrates, indicating that the sol–gel nanopatterning method offers a promising route for translation to future clinical orthopedic implants.

Highlights

  • Arthroplasty is one of the greatest triumphs in modern surgery

  • We found that bone markers (osteopontin (OPN) and osteocalcin (OCN)) from STRO-1 enriched human skeletal stem cells (SSCs) seeded on the materials were significantly higher on pillars as compared to other substrates, Figure 2B

  • We have shown that the developed sol−gel is effective in transferring features in a nonstringent, high throughput manner onto the surface of titanium

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Summary

■ INTRODUCTION

Arthroplasty is one of the greatest triumphs in modern surgery. In particular, the success of total hip replacement and its costeffectiveness in improving quality of life has led to it being named the “operation of the century”.1−3 there are a number of factors placing an increasing demand on this procedure. Effective modification of orthopedic implants.[11−17] Cells sense surface texture via their adhesion receptor transmembrane, heterodimeric integrin. It is believed that this mechanism is responsible for the osteoinductive capacity of nanopatterned orthopedic devices Using a block copolymer mask, the size of features may be controlled by the molecular weight of the polymer components and the spacing of micelles may be controlled through solvent evaporation Despite this method exhibiting a high degree of control, the disorder scales directly with pitch during self-assembly, so it is facile, it does not enable translation of nanopatterns with the electron-beam precision we previously demonstrated upon two-dimensional polymer substrates. Through combining soft nanoimprint lithography with sol−gel processing, we have enabled a translational nanopatterning process capable of reproducing electron-beam-precise osteoinductive topographies upon nonplanar, large areas of clinically relevant, metal-based substrates

■ METHODS
■ CONCLUSIONS
Findings
■ REFERENCES
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