High-dose irradiated allografts found to perform similar to standard grafts

New process promises greater sterility with the same properties of fresh frozen allograft.

Issue: February 2007

The recent tissue harvesting scandal and the small, albeit present, danger of contamination has magnified concerns over allograft safety.

Now early research indicates that a new sterilization process using high-dose radiation may produce safer grafts while maintaining tissue integrity. Researchers examining allografts sterilized by the Clearant Process (Clearant Inc.), a technique using a 50 kGy dose of gamma radiation, found comparable knee function and greater sterility with the new process compared to standard 18 kGy irradiated allografts.

"[We] want a safer graft," Fred D. Cushner, MD, of New York said. "The patients want a safer graft. We find the Clearant grafts similar to the other grafts available. The tissue handling is similar [and] they seem to be performing the same. The only difference is it's externally sterilized so we have a better level of comfort and it does carry the sterility label," he said during his presentation at the annual Insall Scott Kelly Institute meeting.

Similar to the processing of standard allografts, Clearant grafts undergo a screening process, antibacterial wash and terminal sterilization, which is unique to the process. While most allografts undergo low-dose irradiation (less than 25 kGy), Clearant-processed grafts receive a 50 kGy dose of radiation.

Irradiating the grafts at 50 kGy gives surgeons the benefit of a fully sterile product. "By using 50 kGy rather than 25 kGy, you can kill resistant spores," Cushner said. "You get complete inactivation of any lipid enveloped viruses and you get 10^-6 logs of inactivation, which can actually label the product sterile. Go look at your allografts. Not all of them are labeled sterile."

He noted that while gamma radiation kills nucleic acid and pathogens, the process also generates free radicals, which can decrease the mechanical strength of tissue. The Clearant Process' key to avoiding this problem is to minimize free radical formation.

"They reduce the temperature and control the Ph, and they use antioxidants to help to battle the free radicals," Cushner said.

Early results

In an ongoing, multicenter study, Cushner and his colleagues found that only six of 200 Clearant grafts implanted in patients failed during 1-year follow-up. One graft failed due to fixation and five failed from re-injury. Yet, he noted that female adolescent patients had a slightly higher failure rate; a finding mirrored in other allograft studies. "But, if you take those out, no significant failures were seen," Cushner said.

The preliminary results revealed one large effusion, which was resolved, and two burns at the incision site. The researchers also found no significant differences in the range of motion, functional hop and IKDC scores of knees implanted with the Clearant grafts and non-operative knees at 6- and 12-month follow-up.

Other early studies also show promising results using Clearant-processed allografts. Researchers at the Insall Scott Kelly Institute found no failures or complications in their first 30 cases using the grafts, Cushner said.

No differences

He also cited a study performed by Warren King, MD, which found no significant differences between patients that received Clearant grafts and fresh frozen tissue regarding range of motion, Lysholm scores and IKDC scores at a minimum 6-month follow-up. MRIs of the 25 patients implanted with Clearant allografts also showed excellent graft incorporation, Cushner said.

A 4-month postop H&E staining obtained from one patient also revealed fibroblast incorporation. "So certainly no concerns raised in this single-surgeon study and no increased laxity noted as well in the postoperative period," Cushner said.

Laboratory testing also showed that the 50 kGy-irradiated tissue provided more sterile and stronger grafts than low dose constructs. In a study to determine efficacy against Clostridium spores, researchers found that a 50 kGy dose produced a sterile environment while doses below 32.8 kGy were characterized as non-sterile. Compression testing also revealed that 50 kGy irradiated cancellous bone plugs withstood greater ultimate compressive stress compared to plugs irradiated at 18 kGy, the dosage for standard allografts. "Well the difference is that even your standard allograft usually gets exposed to some radiation, but it's not protected and that's why they look to be weaker," Cushner said.

He noted that more of the Clearant-processed bone blocks showed minimal damage and biomechanical failure, while more of the 18 kGy irradiated blocks showed moderate and severe damage. Mechanical testing with human bone-patellar ligament-bone grafts also showed greater tensile strength with Clearant processed grafts vs. 18 kGy irradiated tissue (P=.057).

While early clinical results and laboratory testing have yielded encouraging findings, Cusher said that additional study is needed. "Certainly, at this point, we're happy with the results. Further studies and long-term studies are needed, but at this point, we think they are safer and do not react different than a standard allograft."

For more information:
Cushner F, D. Allograft safety. Presented at the 9th Annual Insall Scott Kelly Institute Sports Medicine and Total Knee & Hip Symposium. Sept. 15-17, 2006. New York.
Fred D. Cushner, MD, orthopedic surgeon at Beth Israel Medical Center in New York and the director of the Insall Scott Kelly Institute, 210 East 64th Street, 4th floor, NY, NY, 10021; 212-434-4312. He is on the scientific advisory board for Clearant Inc.