Advances in 3D Printing and Bioprinting May Transform Orthopaedics

Editor’s note: This article is part two of a two-part series on 3D printing in orthopaedics. Part one described the benefits of 3D printing in established, FDA-approved settings. This article describes novel, as-yet-unapproved potential uses of 3D printing in several orthopaedic scenarios.

In addition to the ability to construct complex or one-off orthopaedic devices, 3D printing has the potential to transform the field of orthopaedic surgery. 3D printing is already used in the manufacturing of a variety of FDA-approved drug-delivery products, and it is also being investigated for a variety of potential orthopaedic uses.

Any of these novel uses are experimental or only available through the FDA Investigational Device Exemption (IDE for devices) or Investigational New Drug Exemption (IND for drugs or biologics) programs. Clinicaltrials.gov currently lists 89 active clinical trials involving 3D-printed products, demonstrating the active interest in novel clinical applications of this technology. The use of 3D-printed scaffolds is of special interest for orthopaedic applications. There are two broad types of cell-delivery scaffolds for tissue regeneration: 3D-printed scaffolds with subsequent cell seeding and 3D cells with bioprinted scaffolds with cells incorporated during the printing process.

The medium for printing involves inert materials that permit either the simultaneous printing or later addition of cells to the printed tissue. Examples of these inert materials include hydrogels, microcarriers, tissue spheroids, cell pellets, tissue strands, and decellularized matrix components. The additive printing process allows control of both the macro and micro architecture of the final structure, allowing it to function similar to in vitro tissues.

The complex structures created by 3D bioprinters can be used for a host of medical indications. 3D-bioprinted tissues can be used in preliminary in silico testing of drugs. For example, 3D-printed cardiac tissue could be used to assess the effect of a new drug on cardiac contractility. Ultimately, this technology might someday be able to print entire organs, such as functioning kidneys for organ transplantation. 3D bioprinting of relevant orthopaedic structures, such as a meniscus for a meniscus-deficient knee, could one day be an option. Major challenges yet to be overcome include a mechanism to allow capillary and blood vessel ingrowth into the printed tissue and methods to avoid potential immunologic reaction to an implant. It is also difficult for bioprinted cells to survive the pressures involved in the printing process. These issues were recently reviewed in a study from Wixted et al published in the Journal of the AAOS^®.

Two areas of distinct interest to orthopaedic surgeons are the 3D printing of bone and cartilage. Although surgical options exist to restore articular cartilage, the options fail to reconstruct the complex structure of that tissue. 3D printing might overcome that failure. In vivo animal studies have shown excellent preliminary results. In a study published in Cartilage, Wu et al summarized those early published results, reporting that human clinical trials of certain bioprinted products are appropriate.

Similarly, bone also possesses a unique microarchitecture, and 3D bioprinting could aid in the multitude of situations where new bone formation is required. The scaffold material is most commonly calcium phosphate, which can allow resorption of the calcium scaffold and complete replacement with native bone. Again, early in vivo animal results have been encouraging.

Even more striking is the possibility of 4D printing. This process involves printing structures that can repair or change shape with time in response to conditions such as temperature, pH, or magnetic field. One example in development is a photothermally responsive bone scaffold, which is moldable after exposure to near infrared radiation but changes to a more rigid bone-like analog when subsequently cooled to body temperature.

Regulation of these complex processes will prove challenging. FDA currently regulates 3D printers through the 510(k) process as devices through the Center for Devices and Radiological Health. Approval of the creation of complex tissue structures will most likely be by a Biologics Licensing Agreement through the Center for Biologics Evaluation and Research at the FDA, a historically difficult pathway for new orthopaedic products. Although establishing the safety of such complex innovations will prove challenging, the advantages may well transform current orthopaedic practices.

Stephen Weber, MD, FAAOS, is an orthopaedic surgeon and assistant professor of orthopedics at the Johns Hopkins School of Medicine. He is a former FDA medical officer and a member of the AAOS Devices, Biologics, and Technology Committee.

References

1. Wixted CM, Peterson JR, Kadakia RJ, et al: Three-dimensional printing in orthopaedic surgery: current applications and future developments. J Am Acad Orthop Surg Glob Res Rev 2021;5(4):e20.00230-11.
2. Wu Y, Kennedy P, Bonazza N, et al: Three-dimensional bioprinting of articular cartilage: a systematic review. Cartilage. 2021;12(1):76-92.