Metals have provided the strength, durability, and other characteristics that bone implants require since the inception of orthopedics. The ability of metals to exist in the human body without significant side effects or risk of rejection are via cobalt-chromium super alloys, stainless steels, and titanium alloys – the most commonly used materials in today’s orthopedic devices.

A more recent innovation in metals technology heralds a new era for metals in medical implants: nano-structuring. Scientists from Los Alamos National Laboratory and several institutes in Russia worked together to develop a simple method to modify the internal structure of any metal at the nano-size scale. This is the scale of a cluster of a few hundred, or a few thousand atoms, which is the scale on which many biological processes occur. Modifying metals at this scale allows them to better match and integrate with human bone tissue. Recognizing the potential importance of this discovery, Manhattan Scientifics Inc. has exclusively licensed the patented nano-structuring technology from Los Alamos National Laboratory to make it available for orthopedic implant and other applications.

Understanding this breakthrough is best by comparing the size of the fundamental building blocks of metals with cells, one of the building blocks of the human body. Metals are built with crystals, also known as grains, whose size is typically between 20µm and 80µm, slightly smaller than the diameter of a human hair. Bone cells are smaller than metal grains, generally having dimensions between 4µm and 10µm. Therefore, when bone-forming osteoblast cells attach to the smooth surface of metals, multiple cells bind to a single grain. This is not ideal. Therefore, orthopedic device makers typically modify the metal surface to enhance bone-metal integration. They use chemical etching, bead blasting, or coatings to roughen the metal surface to create smaller scale features that enhance the ability of cells to mechanically-interlock and more firmly attach to the metal. In contrast, nano-structuring changes metals so completely that the fine scale interlocking ability is built in at any surface, as well as throughout the interior volume. The need for additional surface treatment is reduced or eliminated in nano-structured metals. In addition, having the fine scale features throughout the bulk of the metal remarkably improves other metal properties, including strength, cyclic load resistance, corrosion resistance, machinability, and forgability.

Nano-structuring metals also reduce the size of their constituent grains to a range between 0.02µm and 0.40µm. When bone forming osteoblast cells contact a nano-structured metal surface, they cover many grains simultaneously. This offers multiple advantages.

First, an intrinsic roughness corresponds to the grain size. The center of each grain can be likened to a hill, while the boundaries between each grain are like valleys. These topographical features enable sub-micron scale mechanical interlocking between the metal and bone cells. In addition, since the planes of atoms within each grain are oriented differently, each cell experiences not one, but many arrangements of atoms. The energy of each arrangement of surface atoms determines the metal surface energy. Nano-structured metals present a range of surface characteristics and energies to each cell. Furthermore, with smaller grains,

there also exists a much larger volume of metal associated with the boundary

regions between the grains. Atoms in or near grain boundaries possess

significantly higher energy than the bulk of atoms within the grains, because nano-structuring creates special grain boundary structures that have particularly high energies. Research is underway at multiple scientific institutions to understand how the energies of nano-structured metal surfaces and grain boundaries enhance cell attachment.

Researchers have published the results of studies in which they evaluated the growth of fibroblast [1,2] pre-osteoblast [3,4,5] and stem cells [6] on nano-structured titanium [7]. They consistently find that enhanced adhesion and proliferation of cells is, in some cases, by as much as a factor of 20.

Another advantage of nano-structuring is that it greatly increases the strength of metals, without altering their chemical composition. Therefore, increase in the strength of pure metals can go to levels comparable to, and even greater than, today’s high strength alloys. For example, the strength of commercially pure titanium (grade 4) can increase from its typical range of 400MPa to 700MPa, to a range between 1,200MPa to 1,400MPa. This increase allows orthopedic devices such as spinal devices or hip stems to be stronger and more compact. The superior properties and processing of nano-structured metals has been reported by researchers worldwide in the more than 6,000 scientific publications, addressing virtually every class of metal.