Brian J. Cole, MD, Receives OREF Clinical Research Award for Research on Osteochondral Allograft Transplantation

The 2025 Orthopaedic Research and Education Foundation (OREF) Clinical Research Award was presented to Brian J. Cole, MD, MBA, FAAOS, for his collaborative effort over the past 25 years to advance osteochondral allograft (OCA) transplantation to treat cartilage and bone defects in the knee. Dr. Cole and his team applied translational basic science and clinical research to study allograft procurement, processing, preservation, implantation, surgical technique, and decision making. What was once a niche procedure performed at select academic centers is now considered the most common, reliable, and reproducible method for joint restoration in patients who present with pain and dysfunction.

Knee cartilage and bone defects can cause significant pain, swelling, and reduced mobility and are often a result of localized cartilage loss or early-stage osteoarthritis. Cartilage defects of the knee are common and estimated to be present in 4.2 percent of the general population, 6.2 percent of patients aged 40 years or younger, and up to 36 percent of athletes. An OCA transplantation is a procedure where donor cartilage and bone replace damaged regions of a joint to restore its normal architecture. The procedure is unique in its ability to closely restore both the structural integrity and biological attributes of the native cartilage and bone in a single procedure without associated donor-site morbidity.

OCA transplantation is particularly suited for younger patients with limited areas of damage and is an option for individuals who want to remain active and are not candidates for knee replacement. Use of the procedure has surged during the past two decades, increasing 245 percent from 2005 to 2011 and an additional 160 percent from 2010 to 2016.

“When I finished my training in 1997, there was a paucity of solutions available to treat patients with articular cartilage or meniscal deficiency,” said Dr. Cole, who is endowed professor and acting chair of the Department of Orthopaedics at Rush University Medical Center and director and founder of the Rush Cartilage Restoration Center in Chicago. “While we had early exposure to cell-based cartilage transplantation and other commonly performed procedures such as articular cartilage debridement and microfracture, the orthopaedic community did not have a firm understanding of procedural outcomes or indications leading to unpredictable results. In 1998, our goal was to create a multidisciplinary approach to joint preservation and a comprehensive registry to track results from all procedures since some of the techniques were new, and we were early in the process of developing treatment algorithms without data to support evidence-based decision making.”

Dr. Cole and his team, Jorge A. Chahla, MD, PhD; Susanna G. Chubinskaya, PhD; Ron Gilat, MD; and Adam Yanke, MD, PhD, all associated with Rush University Medical Center, and Rachel M. Frank, MD, FAAOS, with the University of Colorado, Denver, spent nearly three decades studying virtually every aspect of the procedure. They aimed to enhance clinical understanding and technical precision for better results by addressing questions about graft preservation, handling, instrumentation, sizing, donor analysis, and patient outcomes. Enhanced outcomes include the ability to treat athletes at the highest level of sports participation.

Optimal preservation: cell viability and rewarming
“Preserving the cells is paramount to graft viability, and the process is highly time-sensitive,” Dr. Cole said. “One of our early landmark papers focused on determining how long a graft maintains a high rate of viable chondrocytes after donor-tissue procurement. Historically, the window from donor death to graft implantation was limited to 7 days. This created significant logistical challenges when considering the breadth and complexity of steps involved in obtaining a properly sized graft and logistically scheduling a surgical procedure.”

By studying the effects of time on OCA health during the cold preservation process, the team discovered that cell viability was >95 percent at 14 days, 75 to 98 percent at 21 days, and 65 to 90 percent at 28 days, suggesting cold-preserved OCA material should be implanted within 28 days of harvest. This discovery was awarded a Career Development Award in 2001 by OREF as a testament to the future impact of this work.

The graft must also be removed from cold preservation, raising the critical question of the optimal rewarming process. The team discovered that gradually rewarming the graft in stages (4 degrees Celsius to 25 degrees Celsius to 37 degrees Celsius) and reducing nitric oxide production through nitric oxide synthase inhibition at the time of implantation can minimize the loss of chondrocytes’ metabolic function. As a result, the gradual rewarming of fresh OCA grafts has now become the standard practice in surgical procedures, and the team is investigating further methods to enhance cell viability at the time of graft implantation.

Avoiding detrimental effects of thermal energy
When power instruments are used for drilling during surgery, thermal energy or heat from the instruments can have a detrimental impact on cell viability. To minimize the impact of thermal energy, the team made numerous discoveries. Highlights include:

• Using bipolar radiofrequency energy (RFE) on human articular cartilage specimens increased the depth and width of chondrocyte death. As a result, knee preservation surgeons now avoid or minimize using RFE devices near cartilaginous surfaces during arthroscopic and open procedures.
• Thermal chondroplasty performed with a 37-degree Celsius lavage solution resulted in less depth of chondrocyte death and smoother cartilage surfaces than when a 22-degree Celsius solution was used, underscoring the importance of controlling the temperature of lavage solution.
• During OCA plug preparation, chondrocyte viability is improved when the graft is submerged in saline relative to traditional bulb irrigation (72 percent whole plug chondrocyte viability with graft submersion versus 61 percent whole plug chondrocyte viability with bulb irrigation, P = 0.003; unpublished data). The current best practice is to harvest the OCA plug with the allograft fully submerged in saline under drill mode to maximize efficiency and minimize thermal damage.

Removal of immunogenic elements
A concern with the use of allograft tissue is the potential for an antibody-based immunogenic response, which may develop postoperatively and compromise graft integrity and longevity. To address this, the team explored techniques to remove immunogenic elements from the bone marrow by cleansing the graft in the OR. Based on their work, methods such as pulse lavage with irrigation fluid and high-pressure carbon dioxide are now used to clean the graft thoroughly.

The team hypothesized that cells within bone, particularly those attached to articular cartilage, may contribute to inflammation and related complications. By examining the healing process over time, they identified a potential link between immunogenicity and the presence of these cells within bone. Based on these findings, they recommend thorough cleaning of bone to mitigate adverse effects and to improve surgical outcomes.

Augmentation with orthobiologics
The team looked at ways to improve how donor bone heals within the recipient socket, specifically using growth factor therapy, mainly concentrated bone marrow aspirate (cBMA) taken locally from the bone marrow of patients at the time of surgery that is spun down and concentrated to help improve graft integration. Their studies showed that patients whose plugs were soaked in cBMA had less pain at 1 year postoperatively with fewer cysts identified by CT scan at 6 months. In a separate laboratory collaboration, they found that deep cleaning of OCA with high-pressure carbon dioxide better removes moisture and increases graft porosity, leading to greater cBMA saturation and uptake, optimizing graft biology and subsequent bone integration.

“While we’ve made remarkable advancements in the proper handling, procurement, and preservation of grafts, as well as in augmenting the instrumentation and the healing response, there is still much work to be done to understand the direct impact on clinical outcomes, as this requires time,” Dr. Cole explained. “One of the achievements I’m most proud of is our ability to consult with a patient, listen to their story, and predict with reasonable probability how likely they are to respond to this procedure. Although no outcome in orthopaedic surgery is guaranteed, we narrowed the variability in outcomes through this evidence-driven process. We now know that individuals ranging from recreational to professional athletes stand to benefit from OCA transplantation when properly indicated and all comorbidities are addressed properly. Receiving the OREF award is an incredible honor, not just for me but for the hundreds of authors who contributed to this work. It’s a privilege to be part of a multidisciplinary effort that transforms patient care, and the award reaffirms the meaningfulness of the work and fuels our passion for discovery and innovation.”

Jennifer Lefkowitz is a freelance writer for AAOS Now.

For a list of disclosures, funding, and conflicts of interest, email media@aaos.org.

References

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3. McCormick F, Harris JD, Abrams GD, et al: Trends in the surgical treatment of articular cartilage lesions in the United States: an analysis of a large private-payer database over a period of 8 years. Arthroscopy 2014;30(2):222-6.
4. Williams JM, Virdi AS, Pylawka TK, et al: Prolonged-fresh preservation of intact whole canine femoral condyles for the potential use as osteochondral allografts. J Orthop Res 2005;23(4):831-7.
5. Pylawka TK, Virdi AS, Cole BJ, et al: Reversal of suppressed metabolism in prolonged cold preserved cartilage. J Orthop Res 2008;26(2):247-54.
6. Cole B, Yanke A: Osteochondral allograft reaming significantly affects chondrocyte viability. In press. AJSM 2025.
7. Allahabadi S, Haneberg EC, Elias TJ, et al: Osteochondral allografts: pearls to maximize biologic healing and clinical success. Arthrosc Tech 2023;12(12):e2281-7.
8. Atzmon R, Chang W, Chan C, et al: The effect of pressurized carbon dioxide lavage on osteochondral allograft preparation: a comparative study. Submitted for publication. 2024.