JAAOS® Technology Overview Simplifies cBMA Harvesting and Processing to Improve Fracture Healing

With the annual number of reported fractures in the United States projected to increase by at least 10 percent over the next decade due to a growing elderly population, it is crucial to optimize fracture healing for patients with delayed or impaired bone union. Biologic-based interventions, such as concentrated bone marrow aspirate (cBMA), provide a promising solution to improve recovery outcomes and reduce the costs associated with the burden of fracture care. However, determining the most appropriate of the available technologies to harvest and process human cells can be overwhelming.

Philipp Leucht, MD, PhD, orthopaedic trauma surgeon at NYU Langone Orthopedic Hospital and member of the AAOS Committee on Devices, Biologics, and Technology, along with his colleague Devan Mehta, MD, chief resident at NYU Langone Orthopedic Hospital, developed a technology overview for the May 15 issue of the Journal of the AAOS^® (JAAOS^®). The article, titled “Technology Behind Cell Therapy Augmentation of Fracture Healing: Concentrated Bone Marrow Aspirate,” focuses on the technology available to ensure proper preparation and use of cBMA to enhance fracture healing in patients.

“We wanted to approach this article differently, offering a comprehensive technology overview instead of focusing solely on the clinical evidence,” Dr. Leucht said. “Instead of navigating through numerous product guides and publications, the JAAOS article provides orthopaedic surgeons, particularly those less experienced in this area, with a greater understanding of the available systems to deliver high-quality, cutting-edge care.”

As a surgeon-scientist, Dr. Leucht has dedicated the past 20 years of his career to researching stem cell biology. His work delves into the nature of these cells, their decline with age, and potential rejuvenation methods. This foundational research has shaped his approach to fracture repair, focusing on the cellular biology involved. By reintroducing stem cells into fracture sites, whether through bone grafts or cBMA, he aims to enhance the healing process.

Importance of cBMA
Bone marrow aspirate is an autologous composition containing skeletal stem and progenitor cells (SSPCs) and growth factors vital for bone renewal and regeneration.

“The most precise way to pinpoint and isolate a stem cell is through flow cytometry; however, this technique cannot be used in the operating room,” Dr. Leucht explained. “Instead, we use a needle to aspirate the bone marrow and put the cells in a centrifugation system that separates cells (e.g., fat, liquid, red blood cells, platelets) by density, which concentrates the number of osteogenic cells per unit of volume.” The result is cBMA, which can either be applied or injected directly into a fracture site or combined with a graft or graft substitute for osteoconduction and mechanical support, in addition to the cBMA’s osteogenic and osteoinductive properties.

Dr. Leucht added, “The use of cBMA is a newer approach that allows orthopaedic surgeons to intervene earlier, addressing biological deficiencies in fractures and promoting bone union less invasively. Clinically, cBMA therapy is a potential alternative to the current ‘gold standard’ of autologous bone graft, especially since cBMA can be used alongside a graft expander such as cancellous chips, overcoming the limitations associated with autograft harvesting.”

Harvesting and processing techniques
The literature has presented various protocols for harvesting and preparing cBMA based on industry-sponsored studies or personal experiences and surgical abilities, as there is no standardized procedure. However, the overarching concepts behind the techniques of isolating and using cBMA are uniform, so this area is primed for future investigation. Various sites in the body (e.g., anterior and posterior iliac crests, ilium, proximal humerus, proximal tibia, distal femur, distal tibia, sternum, mandible, calcaneus) can be aspirated for bone marrow with a syringe that is heparin-loaded to prevent sample clotting.

To increase the odds for a greater yield of progenitor cells within a certain cohort, research suggests using the anterior or posterior iliac crest. Notably, the posterior iliac crest surpasses the anterior counterpart in both volume and 1.6 times greater yield of progenitor cells. Additionally, when compared to those from the proximal tibia, SSPCs from iliac crest bone marrow have a significantly higher osteogenic capability.

“It’s important to note that higher aspirate volumes do not equate to higher cell concentrations,” Dr. Leucht advised. “When you pull too much, you’re diluting the stem cell concentration with peripheral blood and you’re not going to concentrate anything meaningful.”

Instead, research supports using a small syringe (e.g., 10 ml) and obtaining small aspirates (1 to 4 ml), redirecting the needle into a new area to aspirate another milliliter and repeating the process until there is enough for the specific centrifuge being used. Although there is no set standard for the total volume of bone marrow aspirate required for cell-based therapies, various systems can process anywhere from 30 to 300 ml of bone marrow at once. He added, “With a solid number of stem cells in the initial aspirate, it is easier to concentrate that number by centrifugation.”

According to Dr. Leucht, there are two types of commercial centrifugation systems available:

• The first type of system relies on a manual buffy coat extraction protocol, and the user must manually extract and re-suspend different cellular layers as desired. Although this system allows for the surgeon to have control over the harvested material, human error can cause variation in extracted material. Additionally, manual extraction increases the risk of infection and contamination.
• The second type involves fully automated closed-loop systems in which the syringe containing bone marrow aspirate is connected to a device. Parameters, such as final volume, can be set by the user via computer, and the system uses an optical sensor to evaluate bone marrow aspirate and separate layers automatically after centrifugation.

Dr. Leucht typically recommends closed-loop systems. “This technique minimizes the risk for contamination and subsequent infection because the final product is delivered automatically in a syringe without any manual intervention,” he explained. In addition to a lack of standardized technology, patient factors, such as age and comorbidity, can also impact the viability and function of harvested SSPCs.

He advised on the importance of being clear and setting realistic expectations. “While the idea of cell therapy sounds impressive and promising, patients need to understand the realities,” Dr. Leucht said. “If a patient’s fracture hasn’t healed, it indicates that their body, by no fault of their own, isn’t healing properly. As a person ages, the chances of harvesting a sufficient number of cells diminishes. It can be a difficult truth to share, but it’s important for them to understand.”

Early research on cBMA demonstrates promising outcomes. However, it is important for future research to elucidate how patient factors such as age and comorbidities and a selection of protocol standardization and processing techniques impact the viability of cBMA.

Jennifer Lefkowitz is a freelance writer for AAOS Now.

References

1. Amin S, Achenbach SJ, Atkinson EJ, et al: Trends in fracture incidence: a population-based study over 20 years. J Bone Miner Res 2014;29(3):581-9.
2. Leucht P, Mehta D: Technology behind cell therapy augmentation of fracture healing: concentrated bone marrow aspirate. J Am Acad Orthop Surg 2024;32(10):e476-81.