SUPPLEMENT ARTICLE Nanotechnology and Bone Healing Edward J. Harvey, MD, MSc, FRCSC,* Janet E. Henderson, PhD,† and Srikar T. Vengallatore, PhD‡ Summary: Nanotechnology and its attendant techniques have yet to make a significant impact on the science of bone healing. However, the potential benefits are immediately obvious with the result that hundreds of researchers and firms are performing the basic research needed to mature this nascent, yet soon to be fruitful niche. Together with genomics and proteomics, and combined with tissue engineer- ing, this is the new face of orthopaedic technology. The concepts that orthopaedic surgeons recognize are fabrication processes that have resulted in porous implant substrates as bone defect augmentation and medication-carrier devices. However, there are dozens of applications in orthopaedic traumatology and bone healing for nanometer-sized entities, structures, surfaces, and devices with characteristic lengths ranging from 10s of nanometers to a few micrometers. Examples include scaffolds, delivery mechanisms, controlled modification of surface topography and composition, and biomicroelectromechanical systems. We review the basic science, clinical implications, and early applications of the nanotechnology revolution and emphasize the rich possibilities that exist at the crossover region between micro- and nanotechnology for developing new treatments for bone healing. Key Words: nanotechnology, bioengineering, scaffold, fracture, bone, biomicroelectromechanical (J Orthop Trauma 2010;24:S25–S30) INTRODUCTION The current literature is often confusing when trying to understand what ‘‘nanosized’’ refers to because authors often wander back and forth across nano-, micro-, and macroconcepts in the same manuscript. To bring nanosized into perspective, Figure 1 1 shows the relative sizes of many body structures. The narrowest definition of nanotechnology refers to the science of manipulation of single atoms, rather than groups of atoms, and as such is probably practiced by only a select few laboratories in the world. A broader definition of nanotechnology with far more relevant applications to the health sciences includes structures at the grouped atom level up to approximately 100 nm. DNA is 2.5 nm wide and a cell membrane is 8 to 10 nm. Bone-forming osteoblasts are typically 25 mm in size. The ability to control and manipulate materials at the level of atoms and molecules (with characteristic length scales of 1–100 nm) and integrating such exquisitely tailored materials within larger (micro- and macroscale) systems for engineering and medical applications are two of the defining signatures of nanoscience and nanotechnology. Orthopaedic surgeons have long recognized the need for readily available, cost-effective bone substitutes to repair large defects. Synthetic tissue grafts are needed to overcome the limitations of traditional allografts and autografts that include the risk of rejection, infection, pain, and limited availability. 2 Bioresorbable and porous scaffolds, seeded with appropriate cells and osteogenic factors, could provide a template for native tissue regeneration. Some are applicable to the traumatologist. These include nanoparticle-composite bone tissue-engineering scaffolds with enhanced mechanical properties, nanofibrous scaffolds that modulate cellular function, and nanoparticles that deliver osteogenic genes or growth factors. Missing from this list is the use of protein manipulation at the implant– osteoblast interface to promote bone healing. Most of these processes will eventually be monitored by biomicroelectro- mechanical systems (bioMEMS) or bioNEMS, which are micro-/nanosized implants under development for real-time biologic monitoring and treatment delivery. 3 Nanostructured Scaffolds for Bone Repair The high failure rates 2,4,5 associated with the use of allograft bone are costly in terms of revision procedures and patient recovery. The significant limitations associated with the use of autograft and allograft bone to repair large skeletal defects have prompted intense investigation in the develop- ment of biomimetic substitutes for bone tissue engineering. Native bone is a complex composite material with structures that range from the nano- to microscale. Type I collagen fibrils and hydroxyapatite crystals are the two major components of bone and are individually less than 50 nm in diameter. They are bundled together in 500-nm fibrils, which are further grouped into fibers and that form the structured lamella around Haversian canals (3–7 mm) in cortical bone. The functional Accepted for publication November 10, 2009. From the *Orthopaedic Trauma, McGill University, and J.T.N. Wong Labs for Bone Engineering, Montreal, Quebec, Canada; †Medicine and Surgery, Orthopedic Research, RI-McGill University Health Centre, and J.T.N. Wong Labs for Bone Engineering, Montreal, Quebec, Canada; and ‡Advanced Materials for Micro/Nanosystems, Department of Mechanical Engineering, McGill University, Montreal, Quebec, Canada. A portion of this work was funded by the Canadian Institutes of Health Research, (CIHR), Fonds de la recherche en sante ´ du Que ´bec (FRSQ), the Canadian Orthopaedic Foundation (COF), and the National Science and Engineering Research Council of Canada (NSERC). Dr. Harvey is a Chercheur Clinicien-Senior of the FRSQ and ST Vengallatore holds a Canada Research Chair in Advanced Materials for Micro- and Nanosystems. Reprints: Edward J. Harvey, MD, MSc, FRCSC, Division of Orthopaedic Surgery, MUHC–Montreal General Site, 1650 Cedar Avenue, Room B5. 159.5, Montreal, Quebec, Canada H3G1A4 (e-mail: edward.harvey@ much.mcgill.ca). Copyright Ó 2010 by Lippincott Williams & Wilkins J Orthop Trauma  Volume 24, Number 3 Supplement, March 2010 www.jorthotrauma.com | S25