On a mission for the next-generation load-bearing implants

Although bacterial colonization of orthopedic implants is a leading cause of failure and clinical complexities for load-bearing metallic implants, traditional approaches, such as topical or systemic administration of antibiotics, may not efficiently prevent colonization, especially in the case of secondary infection, often resulting in surgical removal of implants, and severe cases, even limb amputation.

In International Journal of Extreme Manufacturing, Prof. Amit Bandyopadhyay's team proposed a simple yet very effective solution to this problem. They suggested fortifying titanium (Ti) implants with 3 wt.% copper (Cu) via multi-material additive manufacturing, which not only inherently protects the implant against bacterial infection but also enhances biocompatibility by adding tantalum (Ta) to facilitate early-stage osseointegration.

"A recent World Health Organization report stated the alarming fact that around 700 000 deaths occur annually due to antimicrobial resistance (AMR). If effective clinical remedies are not found, the number is projected to surge to as many as 10 million deaths per year by 2050—higher than 8.2 million deaths per year due to cancer, making AMR a substantial global economic burden," said Prof. Amit Bandyopadhyay, the Boeing Distinguished Professorship at the Washington State University, who is both the first and corresponding author of this study.

Moreover, the mortality rate for prosthetic joint infection (PJI) stands at a striking 87.3%, which is greater than that for colorectal and lung cancer and comparable to those for breast cancer (89%). Clearly, PJI has evolved into an urgent and critical clinical challenge that requires immediate attention.

Unfortunately, existing approaches to address these issues are not always sustainable, leading to recurring infections even after revision surgery. The mutual exclusivity of high infection rates, revision surgeries, and out-of-pocket costs associated with such procedures further complicate the problem. Thus, there is a pressing need for implants that are self-sufficient in preventing PJI and mitigating the complexities of revision surgeries.

Two critical challenges remain unaddressed in today's metallic material selection for these biomedical applications: infection control and enhanced biocompatibility. Currently, Ti6Al4V is the most popular metallic biomaterial for load-bearing implants. However, research has also shown that Ti6Al4V lacks biocompatibility compared to pure Ti, and as a result, healing time is delayed, affecting patients with compromised bone health. On the other hand, pure Ti shows excellent biocompatibility, but its mechanical properties are unsuitable for load-bearing applications.

"So the question is whether we can design an alloy composition between pure Ti and Ti6Al4V with biocompatibility similar to pure Ti while mechanical strength is close to or similar to Ti6Al4V. Furthermore, can that composition be additively manufactured explicitly to design patient-specific load-bearing implants as an alternative to Ti6Al4V?" Prof. Bandyopadhyay said.

The search to replace Ti6Al4V for better biocompatibility has led researchers to develop various multifunctional materials like Ti-Cu alloys, which can improve the chances of a successful implant, reduce healthcare costs, and increase value-of-product. However, most studies have only evaluated Ti implants alloyed with ≥ 5 wt.% Cu for bacterial resistance fabricated via powder metallurgy. Such high Cu content in the implant materials has raised increasing concerns among the scientific community.

Furthermore, these studies often overlook the potential cytotoxicity associated with elevated Cu levels or fail to evaluate strategies for comprehensively improving the early-stage osseointegration ability of the implants.

"Adding Cu may alleviate the issue of bacterial colonization and improve implant biocompatibility, but we must also consider the potential impact of Cu on bone response when implanted in vivo. A promising solution should be a functional material that is universally applicable but simultaneously addresses various drawbacks contributing to poor biocompatibility. Therefore, we are dedicated to exploring the extent of alterations and establishing an alternative to mitigate any compromise in biocompatibility." Prof. Bandyopadhyay commented.

To this end, Prof. Bandyopadhyay's team fabricated Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders via laser powder bed fusion (LPBF). Besides, a 10 wt.% Ta (10Ta) and 3 wt.% Cu (3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance.

Then, they investigated the additively manufactured implants to assess their resistance efficacy against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 hrs, and their dedication paid off with impressive results: their fabricated Ti3Al2V-10Ta-3Cu alloy displayed remarkable synergistic effect on improving both in vivo biocompatibility and microbial resistance. Notably, it demonstrated an antibacterial efficacy 80% higher than traditional CpTi and Ti6Al4V, marking a significant leap forward to more efficient individualized therapy for the next generation of load-bearing metallic implants.

"Our novel Ti3Al2V alloy exhibits excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics compared to its counterparts, CpTi and Ti6Al4V," Prof. Bandyopadhyay said. "This achievement is due to the deliberate reduction of the Vanadium (V) and Aluminum (Al) components from Ti6Al4V, as these elements do not add any significant biological properties to these alloys. Importantly, these improvements are realized without compromising any mechanical properties of these alloys."

Prof. Bandyopadhyay agrees that further device-level, longer-term in vivo studies with large animals are needed before these materials can be used for humans. Also, he would like to see continued efforts to advance compositional modification to reach >99% efficacy to prevent bacterial colonization. "But ultimately, we feel a material like Ti3Al2V-10Ta-3Cu could improve patients' postoperative quality of life and reduce the number of revision surgeries that arise from multiple scenarios, including bacterial infection," Prof. Bandyopadhyay said.