Minimize waste of fresh cartilage graft tissue during the COVID-19 pandemic
Click Here to Manage Email Alerts
Logistical considerations surrounding COVID-19 testing have become part of the weekly routine of orthopedic surgeons.
While the restrictions of COVID-19 regulations can cause frustration, these must be adhered to given there are mortality rates as high as 20% in COVID-19-positive patients undergoing elective surgery, a study by Shaoqing Lei and colleagues showed. This has particular implications for surgeons who perform cartilage restoration. Although it is rare for patients scheduled for osteochondral allograft (OCA) or the second stage of autologous chondrocyte implantation (ACI) to become COVID-19-positive in the immediate preoperative period, if this occurs, it poses a problem when coordinating delivery of the expensive tissues used for these two procedures. COVID-19 vaccinations are now becoming available. However, surgeons will continue to face these concerns for the better part of this year until mass vaccination of the general population occurs.
Recently, there has been an increase in use of living cell/tissue-based procedures to manage cartilage defects that are time-critical. ACI involves the harvest of autologous chondrocytes, ex vivo expansion of these cells and their subsequent implantation during a second procedure. According to a study by Seth K. Williams, MD, and colleagues, most, but not all, fresh OCAs must be implanted within 28 days of when these are harvested from recently deceased patients, with a 14-day initial testing period to further narrow this window of possible transplantation. Therefore, it is paramount that surgeons have knowledge of their providers’ OCA shelf life.
In addition to OCA being in limited supply, these procedures are costly. A study by Kyle R. Sochaki, MD, and colleagues showed implant-related costs exceeded $10,000 for OCA, as well as ACI.
Surgical cancellation dilemma
The last-minute cancellation of cartilage restoration surgery, and loss of graft tissue in particular, when a positive COVID-19 test result is received raises some important questions:
Could this situation have been prevented with different testing strategies or graft manufacturing protocols?
Can the graft be returned and reprocessed for use elsewhere or does it need to be discarded?
Who is responsible for the cost of the graft in these situations?
Optimizing all the logistical factors surrounding cartilage restoration in the environment of the COVID-19 pandemic can be challenging, but it is of utmost importance to avoid wasting these valuable grafts. Herein, we discuss these questions and offer solutions from experts within the cartilage restoration community.
Considerations for minimal graft loss
There are three key processes that may influence whether time critical grafts can be used. These include the processes for prevention of and testing for COVID-19 in the perioperative period; optimizing the manufacturing, release and delivery of grafts; and post-graft release procedures (Table).
Prevention
Lei and colleagues reported perioperative mortality of about 20% in COVID-19-positive patients. Therefore, surgery for these patients is reserved for emergent, life-threatening situations. While cartilage restoration can be time-sensitive when tissue grafts are involved, Francesca Vannini, MD, PhD, and colleagues found it would be unacceptable to proceed with surgery for this relatively elective surgery. Additionally, every effort should be made to ensure the safety of the surgical team. Cartilage restoration typically occurs at outpatient centers where the required personal protective equipment needed to interact with COVID-19-positive patients is less readily available.
To avoid this situation, many institutions have developed protocols for testing patients preoperatively, usually within 1 week prior to the surgery. Having a blanket protocol for all elective surgery is a disservice to the surgeon who performs surgery that involves grafted tissues. Ideally, if a case were to be canceled due to the patient testing positive for COVID-19, the test results would be received early enough for the case to be canceled before the graft would need to be discarded. Therefore, testing that takes place the week leading up to surgery provides minimal time in the case of a positive test result to cancel or repurpose cartilage grafts. However, COVID-19 testing of patients that is done too early provides more time for the patient to become infected between the day of the test and the day of surgery. A balance between the two competing problems should be established.
A number of centers have transitioned to a protocol for patients scheduled for OCA or ACI procedures to be tested 2 weeks before surgery, to quarantine themselves leading up to surgery and then undergo a rapid test on the day of surgery. This could potentially reduce the risk of graft wasting. However, this has limitations, which include higher cost and poor patient compliance. Overall, testing strategies to minimize graft wasting should be utilized, keeping in mind that patient safety takes priority.
Manufactured optimization
Autologous cultured chondrocytes on porcine collagen membrane (MACI) is performed by taking a cartilage biopsy. These cells are expanded in the laboratory and then embedded into a collagen membrane. The timing of embedding the cells is determined by the proposed date of surgery because the cells can be cryogenically preserved during the weeks leading up to the date the cells are needed. Once the membrane is assembled, it has approximately 6 days before it expires. Therefore, surgical cancellations within this timeframe prevent the use of the membrane. Fortunately, the manufacturer typically has additional cells from the expansion on hand to allow for a new membrane to be produced. However, if there are not enough cells for a new membrane, the process must start from the beginning with a new biopsy.
MACI production can be optimized during the COVID-19 pandemic to minimize the risk of having to subject the patient to an additional surgery to reobtain the biopsy. Additionally, communication between the surgeon and the MACI manufacturer is of utmost importance. Knowing the testing protocol can impact when the cells are embedded into the membrane. For example, if a patient is tested 5 days before surgery, delaying MACI production until the patient is confirmed to be COVID-19-negative would be ideal. This would still provide ample time for processing and shipping, while eliminating the risk of unnecessary wastage.
Manufactured optimization: OCA
OCA scheduling is less flexible than ACI scheduling because it is less predictable when a graft will become available. Patients typically provide a treatment time window that would be ideal for them before the search for a match begins. Once matched, grafts typically have 28 days from harvest to implantation for optimized cell viability, according to Williams and colleagues. Usually, 1 to 2 weeks of this timeframe are used for processing and testing, which leaves a 2- to 3-week timeframe in which the surgery can take place. If surgery is canceled during this timeframe, it leaves few options for the patient other than rescheduling and restarting the graft search process. Again, communication between the surgeon and manufacturer can minimize the risk of these grafts being wasted. Having a graft prepared with as much time left in this timeframe as possible would be beneficial. For example, if a graft with 3 weeks of viability remaining is ready, the patient can be tested at that point. Even if the patient is found to be COVID-19-positive, the surgery can be scheduled after the patient undergoes the standard 2-week quarantine and the graft would still be viable.
This requires more flexibility on the part of the surgeon and patient. However, it would reduce the risk of unnecessary graft wastage. In general, medial and lateral tibial condyles require that surgery be scheduled 4 to 6 weeks in advance, while patella and tibial plateau graft procedures are scheduled 10 to 12 weeks in advance.
MACI, OCA post-graft release options
Due to the individualized nature of the MACI implant, there is unfortunately not much use for the graft when a case is canceled after the graft has been shipped. Knowing the increased risk of graft wastage during the COVID-19 pandemic, increased emphasis should be placed on chondrocyte expansion. While wasting a MACI graft would result in unnecessary spending and resources, having additional cells can prevent the patient from a subsequent biopsy. These additional cells can be cryogenically preserved until a time when the patient is better suited for surgery.
OCAs are typically shipped 2 days prior to surgery. If a patient tests positive for COVID-19 in this timeframe, the most important step is to ensure that the box has not been opened. If it has been opened, the graft must be used at that facility. If it has not been opened, the supplier will typically attempt to facilitate a transfer of the graft to another facility. Once the box has been opened, however, a transfer is no longer allowed. The graft itself is not returned to the manufacturer as it would not be able to be re-processed before its expiration date. The financial loss in the instance when the graft cannot be used is usually divided between the facility and the graft supplier, but this depends on graft company. One additional consideration for both OCA and ACI procedures is to donate the unusable tissue for educational purposes to be implanted by surgical trainees in the laboratory.
Conclusion
Optimization of the logistical aspects of MACI and OCA surgery is paramount during the COVID-19 pandemic to avoid graft wastage. Testing strategies should prioritize patient safety, but also attempt to identify positive cases before graft release. Communication between the surgeon and graft companies can help optimize processing. Knowing options for return and reprocessing of grafts can minimize graft wastage in worst-case scenarios.
References:
COVIDSurg Collaborative. Lancet. 2020;doi:10.1016/S0140-6736(20)31182-X.
D'Apolito R, el al. J Arthroplasty. 2020;doi:10.1016/j.arth.2020.04.057.
Lei S, et al. E Clinical Medicine. 2020;doi:10.1016/j.eclinm.2020.100331.
Sochacki KR, et al. Cartilage. 2020;doi:10.1177/1947603520967065.
Vannini F, et al. Int Orthop. 2020;doi:10.1007/s00264-020-04741-4.
Williams SK, et al. J Bone Joint Surg Am. 2003;doi:10.2106/00004623-200311000-00008.
For more information:
Jack Farr, MD, can be reached at OrthoIndy, 1260 Innovation Pkwy., Suite 100, Greenwood, IN 46143; email: jfarr@orthoindy.com.
Andrew S. Gudeman, MD, an orthopedic surgery PGY 2 resident at Indiana University School of Medicine, can be reached at 340 W. 10th St., Fairbanks Hall, Suite 6200, Indianapolis, IN 46202; email: asgudema@iu.edu.
Iain R. Murray, FRCS, PhD, a clinical fellow in orthopaedic sports medicine at Stanford University, and Seth L. Sherman, MD, associate professor of orthopedic surgery at Stanford University Medical Center can be reached at 450 Broadway St., Redwood City, CA 94063. Murray’s email: imurray@stanford.edu. Sherman’s email: shermans@stanford.edu.
Collapse
Read more about
Click Here to Manage Email Alerts