Could dissolvable metal be the future of medical implants?

Researchers at North Carolina A&T State University reveal the conditions that allow tissue and bone cells to attach and grow on magnesium-based metals, a promising class of implant material.

 

In 2011 alone, more than 1 million procedures were performed to replace knees, hips, and shoulders with artificial “prosthetic” components, according to a 2014 report by the American Academy of Orthopaedic Surgeons. Key to the success of these surgeries is the interaction between the implanted material’s surface and the surrounding tissue. A 2014 PLOS One paper by researchers at the HBCU North Carolina A&T State University provides new insight on how the tissue–and subsequently bone cells–interact with magnesium-based (Mg-based) metals, a promising class of implant material.

The paper’s authors, master’s student Nan Zhao and bioengineering professor Donghui Zhu, belong to the NSF Engineering Research Center for Revolutionizing Metallic Biomaterials, which funded the study. The center aims to “transform current medical and surgical treatments by creating “smart” implants to improve treatments for orthopedic, craniofacial, neural and cardiovascular ailments” and to “revolutionize metallic biomaterials and smart coatings with built-in responsive biosensory capabilities which can adapt to biological changes.” North Carolina A&T is the center’s lead institution, with partner institutions including the University of Pittsburgh, the University of Cincinnati, and the Hannover Medical School in Germany.

The numbers of people requiring prosthetic devices are on the rise worldwide (the figure below shows that trend in Australia). Age, diet, active lifestyles, and environmental factors all contribute to the degeneration of joints and other body parts that either need to be replaced or reinforced. Also on the rise are the types of implanted biomedical devices that deliver medication, monitor body functions, or support failing organs. The pacemaker is one well-known example.

Many medical implants are made from metals, plastics, ceramics–materials that are relatively nonreactive, or inert–so they won’t corrode–and easy to mass-manufacture. Three inert metals, stainless steel, titanium, and cobalt-chrome alloys dominate the medical devices marketplace.

However, the permanence of  inert materials is not always desired. Some surgical procedures require the presence of artificial devices that can safely dissolve in the body after serving their function, eliminating the need for a second surgery to remove the implant. Also, the material can serve as temporary scaffolding for cell growth while the bone is naturally regenerated. For such applications, so-called biocompatible materials–typically biological polymers–are more popular.

As a biomaterial, Mg and its alloys combine the best of metals and biocompatible polymers. Like most metals, Mg is strong and stiff, properties desired in most prosthetics–it is also much lighter than the common implanted metals. And like biocompatible polymers, Mg degrades into products (like the Mg ion) that are (in theory) safely absorbed by the body, and are in some cases even beneficial to the healing process.

But under what conditions would bone cells attach and grow on an Mg-based implant? First, it is important to note, as North Carolina A&T researchers Nan Zhao and Donghui Zhu did in their PLOS One paper, that cells generally don’t interact directly with bare metal materials. Either the material is coated with a biomineral that stimulates biological interaction, or else extracellular-matrix (ECM) molecules, which provide structural support for bone cells, can adsorb onto the material surface–and that depends on the surface properties.

Conducting their experiments in vitro (that is, in a lab setting as opposed to inside the body), Zhao and Zhu varied the surface roughness of two Mg-based samples–a pure Mg metal and an Mg-based alloy–and studied the interaction with collagen, the most abundant ECM protein. Collagen molecules can attach to implant materials and grow into fibrils, which is the form they take in fibrous tissues, like skin, tendons, and ligaments.

The researchers discovered that the initial concentration of collagen molecules, the pH of the solution, the time they allow the collagen to assemble into fibrils, and material surface roughness all affect the final fibril structure, particularly thickness. Curiously, under certain conditions, rougher surfaces provided more surface area for collagen attachment, but their grooves and ridges hampered subsequent cell attachment.

Zhao and Zhu acknowledge the limitations of their in vitro study, which neglected the role of other ECM proteins and cellular conditions essential to collagen assembly. They also do not discuss in detail, as this report does, the cons of Mg-based implants: For example, they may degrade too rapidly and release H2 gas, which could detach the implant, or worse, enter the bloodstream, causing death.

But it’s still early days, and such kinks will more than likely be studied by this research team, and by others. After all, biodegradable magnesium could well be the future of orthopedic implants.