SOFT TISSUES REGENERATION
Repair of Avascular Meniscus Tears with Electrospun
Collagen Scaffolds Seeded with Human Cells
Jihye Baek, PhD,1,2 Sujata Sovani, MS,1 Nicholas E. Glembotski, BS,1 Jiang Du, PhD,3 Sungho Jin, PhD,2 Shawn P. Grogan, PhD,1 and Darryl D. D’Lima, MD, PhD1
The self-healing capacity of an injured meniscus is limited to the vascularized regions and is especially challenging in the inner avascular regions. As such, we investigated the use of human meniscus cell-seeded electrospun (ES) collagen type I scaffolds to produce meniscal tissue and explored whether these cell-seeded scaffolds can be implanted to repair defects created in meniscal avascular tissue explants. Human meniscal cells (derived from vascular and avascular meniscal tissue) were seeded on ES scaffolds and cultured. Constructs were evaluated for cell viability, gene expression, and mechanical properties. To determine potential for repair of meniscal defects, human meniscus avascular cells were seeded and cultured on aligned ES collagen scaffolds for 4 weeks before implantation. Surgical defects resembling ‘‘longitudinal tears’’ were created in the avascular zone of bovine meniscus and implanted with cell-seeded collagen scaffolds and cultured for 3 weeks. Tissue regeneration and integration were evaluated by histology, immunohistochemistry, mechanical testing, and magentic resonance imaging. Ex vivo implantation with cell-seeded collagen scaffolds resulted in neotissue that was significantly better integrated with the native tissue than acellular collagen scaffolds or untreated defects. Human meniscal cell-seeded ES collagen scaffolds may therefore be useful in facilitating meniscal repair of avascular meniscus tears.
Arthroscopic iliotibial band allograft labral reconstruction had promising outcomes at 2 years
At a minimum 2-year follow-up, recently published results showed promising results of arthroscopic iliotibial band allograft labral reconstruction of the hip using a front-to-back fixation technique.
From April 2011 to April 2012, researchers identified 152 hips that underwent arthroscopic iliotibial band allograft labral reconstruction. Surgeons performed the reconstructions using a modified front-to-back fixation method. All patients completed questionnaires to obtain their modified Harris Hip Score, Lower Extremity Function Score, VAS pain scores and patient satisfaction preoperatively and postoperatively.
Overall, 86.2% of hips had complete follow-up at a minimum of 2 years. Researchers noted 70 hips had concomitant procedures performed. At a mean of 17 months after labral reconstruction, results showed 13.7% of hips required revision procedures. Significant improvements were found in all outcome measures from preoperative levels to most recent follow-up in the remaining 113 hips, with the modified Harris Hip score improving by 34 points and the mean Lower Extremity Function Score improving by 27 points.
Results showed VAS pain score improved by 3 points at rest. This score improved by 4 points with average pain with daily activities and by 5 points with sport. Overall satisfaction was rated as a nine out of 10 among patients, according to results.
Graft choices for ACL reconstruction vary among surgeons, athletes
Orthopedic surgeons have several factors to take into account when choosing the appropriate graft for ACL reconstruction in athletes, including which grafts works best for each patient.
“Graft choice is a personal decision to be made by both the patient and the surgeon,” Patrick C. McCulloch, MD, associate professor in the Department of Orthopedic Surgery at Houston Methodist Hospital, toldOrthopedics Today. “There are pros and cons to each of the different choices, and that is where the patient and the doctor need to have a discussion where they weigh these and come to the right graft for a particular situation.”
In choosing the appropriate graft, orthopedic surgeons and patients have the options of using either an autograft or an allograft.
“The main advantage of autograft — of using your own tissue — is the fact that the healing response is probably a lot better and quicker from the time course then using cadaver grafts,” E. Lyle Cain Jr., MD, fellowship director at the American Sports Medicine Institute and founding partner of Andrews Sports Medicine and Orthopedics Center, said.
Among autograft choices, the most commonly used include patellar tendon and hamstring tendon, as well as the quadriceps tendon, according to Brett D. Owens, MD, professor in the Department of Orthopedic Surgery at Brown University Alpert Medical School.
“The other large family of options is on the allograft side, which there are a lot of options, primarily Achilles tendon allograft, patellar tendon allograft and then also hamstring and tibialis tendon allografts,” Owens said.
Although there are several allograft and autograft options available for ACL reconstruction, Owens noted a higher failure rate when allografts are used in young athletes. In a systematic review of eight overlapping meta-analyses, Randy Mascarenhas, MD, FRCSC, and his colleagues found lower re-rupture rates in autografts among multiple studies compared with allografts, but no significant differences in clinical outcomes between the two grafts. More specifically, Cain noted patella tendon graft is chosen by many orthopedic surgeons because it has tissue quality similar to the ACL.
“[The patellar tendon graft] already connects two pieces of bone, whereas other soft tissue grafts connect muscle to bone so it is a different tissue type,” Cain said.
He added, when the patellar tendon is matched with the bone tunnel on the femur and tibia, the bone heals within the bone faster compared with the healing rate of soft tissue.
This bone-to-bone healing with the patellar graft is advantageous for athletes who are interested in returning to activity as quickly as possible, according to Owens. The patellar tendon graft also provides fixation options “with the ability to put interfering screws in and not rely on suspensory fixation, which is sometimes used in hamstring grafts,” he said.
According to McCulloch, there have been reports that patients experienced anterior knee pain when a patellar tendon graft was used in ACL reconstruction.
“One of the concerns for people with patellar tendon grafts is that in the early studies, there was up to a 10% incidence of persistent anterior knee pain, which may be a particular concern for athletes who perform kneeling” McCulloch said.
However, Brian J. Cole, MD, MBA, professor in the Department of Orthopedic Surgery at Midwest Orthopedics at Rush, noted “the incidence of anterior knee pain is not categorically higher in patellar tendon grafts and can occur with any ACL surgery or knee surgery in general.”
“We are doing an analysis of failure rates and complications of ACL surgery in general and patients need to be stratified as to what their relative risk are related to graft choice,” Cole said.
Patients with patellar tendon graft also have reported a little bit more difficulty early on in rehabilitation compared with cadaver grafts, according to Cain.
“Our [graft] choice usually depends on the activity level of the person,” Cain said. “[For] lower-level athletes, weekend warrior and snow skiers, [sometimes] you can use hamstrings or sometimes you can use cadaver graft, whereas in the higher-level athletes, [most] people use patella tendon autograft for their primary choice because of the quicker healing and the tissue properties of the graft itself.”
Compared with patellar tendon grafts, hamstring grafts have donor site morbidity, but Owens noted less knee pain.
“Hamstring grafts also have donor site morbidity primarily with some hamstring weakness,” Owens said. “There can be a little less of an issue with anterior knee pain. The biggest concerns of the hamstring graft are about the fixation strength and the healing.”
Mark E. Steiner, MD, section chief of sports medicine at New England Baptist Hospital, noted allografts in general have less pain and are easier for rehabilitation compared with autografts, but also have an increased risk of re-injury, particularly in college and high school athletes, and pose a theoretical risk of infection transmitted by the graft.
“We should differentiate soft tissue allografts from what are called [bone-patella tendon-bone] BPTB or patellar tendon allografts,” Steiner said. “BPTB allografts have stiffer fixation and possibly better results.”
According to McCulloch, patients may view the various advantages and disadvantages of graft options differently, and should have a say in the choice of graft.
“To an elite level professional athlete, the idea that if they use a patellar tendon graft they will have a stiff and strong graft with the lowest risk of re-rupture, but at the expense of potentially having some anterior knee discomfort and perhaps a little harder rehab in the first few weeks may be a reasonable tradeoff,” McCulloch said. “To someone who is over 40 years old and does not play competitive team sports, they may be perfectly happy choosing an allograft tendon because the allograft tendon has a high success rate and may allow them to get back to work sooner and have no donor site morbidity.”
Steiner noted successful implantation of the graft may be more important than the type of graft used.
“The most important feature of a successful ACL reconstruction is the placement of the graft and the fixation of the graft, more important than the type of graft,” Steiner told Orthopedics Today. “All these grafts are at least 1.5 times as strong as the native ACL to start with, so it is how these are put in that are most important.”
Differences in sports, gender
Several studies have shown the preference for use of patellar tendon autograft among team physicians. In a study published in Arthroscopy, Brandon J. Erickson, MD, Cole and their colleagues found 136 (99.3%) National Football League (NFL) and National Collegiate Athletic Association Division I football team orthopedic surgeons chose autografts, of which 86.1% chose BPTB autografts to treat ACL tears in their starting running back.
Nathan A. Mall, MD, Cole and their colleagues also found 26 (87%) National Basketball Association (NBA) team physicians chose autograft for primary ACL reconstruction, with 81% using BPTB autografts, 12% quadruple hamstring autografts, 4% double hamstring autograft with or without allograft augmentation and 4% quadriceps tendon autograft with bone block. However, results showed allograft was chosen more frequently in the revision setting vs. autograft (57% vs. 43%).
“When we looked at the surgeons who take care of the professional soccer players in the United States and Canada by surveying the Major League Soccer (MLS) team physicians, we found their preference was to use a patellar tendon autograft about 70% of the time,” McCulloch said. “The other 30% usually still used an autograft, but they selected a hamstring autograft.”
Cole said there are regional differences of grafts chosen for athletes with orthopedic surgeons in the United Kingdom commonly using hamstring grafts for professional soccer players, while surgeons on the west coast of the United States tend to use allografts. Cole added that mainstream American sports associations, such as the NFL, MLS and NBA, tend to use patella tendon autograft.
“The important message is there is more than one way of getting it right and you are separating on percentages differences,” Cole told Orthopedics Today. “There is no absolute correct answer, there is just research that suggests potential differences based on age, sport, gender and things of that nature between these grafts, and that is the bell curve.”
When it comes to gender, female athletes experience a higher rate of ACL tears vs. male athletes when performing the same sport, such as soccer and basketball, according to McCulloch.
“The reasons are multifactorial, but [studies] have shown that women have more quad dominance, meaning relatively weaker hamstring to quadriceps strength,” he said. “In fact, programs focusing on improving hamstring strength have been shown to decrease ACL rates in women.”
He continued, noting that due to studies showing hamstring strength does not completely return to normal 2 years after harvest, some orthopedic surgeons are less likely to use hamstring autografts among elite female athletes “out of concern that it may cause some residual weakness in the hamstring which could put them at risk longer term.”
Owens noted most high-volume ACL surgeons who treat athletes tend to be a little more aggressive with their graft choice among their athletic patients compared with non-athletic patients. Steiner also noted athletes should be considered for autografts, specifically patellar tendon autograft which has higher return to sport success than hamstring autograft, while non-athletes should be considered for allografts due to the greater re-injury rate in athletes with allografts. However, Cole noted graft choice should not be solely based on whether the patient is an athlete.
“As a surgeon, if you have an excellent experience with a certain graft choice based upon your specific decision-making criteria, then that remains an experiential decision by the surgeon to achieve his or her highest success rates,” Cole said.
He added, “There are different buckets that people choose and there is no absolute correct answer, but there is a way to look at existing literature to make the best decision in the interest of the patient.”
Risk factors for failure
According to Steiner, re-rupture of the ACL after primary reconstruction can lead to diminished chances of returning to higher level sport.
“A big risk or negative outcome is the loss of more time out of sports and loss of confidence in the knee,” Steiner said. “Athletes after revision reconstruction do not do as well as those after [a] primary reconstruction.”
“To an elite-level athlete, going through ACL reconstruction one time is a traumatic thing and may be costly to their career and to their finances,” McCulloch said. “The idea of having it potentially re-rupture is an appalling complication that should be avoided at all costs.”
However, Cole noted incomplete rehabilitation can contribute to re-rupture of the ACL, and McCulloch said technical error on the part of the orthopedic surgeon also can contribute to ACL reconstruction failure.
“If the graft is not placed in the appropriate position, it may either be subject to undue stress causing it to fail early or to provide poor stability to the knee causing the knee to still be at risk for a recurrent instability event,” McCulloch said.
How an athlete performs in sport activities and returning to sport following ACL reconstruction can also cause risk factors for re-rupture.
“There are certain biomechanical factors in the way that athletes land from the jump and the way they cut and twist and pivot, and those are the things that we try to modify throughout the years with certain prevention programs to try to effect the way mechanically that the knee is stressed during athlete activity,” Cain said.
Independent risk factors for re-rupture include age and being male, with higher failure rates associated in male patients younger than 25 years of age, according to Cole.
“Other risk factors for failure [are] concomitant or associated ligament injury, meniscal injury, alignment,” Cole told Orthopedics Today.
Advice for orthopedic surgeons
Cole said it is most important for orthopedic surgeons to perform a successful ACL reconstruction the first time.
“There are a lot of ways to have a successful outcome independent of the graft choice and statistically that is what should happen,” Cole said.
However, to accomplish a successful operation, orthopedic surgeons need to be comfortable operating with all grafts, according to Steiner.
“I would suggest that the surgeon be able to perform all ACL reconstructions with all the grafts and to respond to the patient’s choice because the differences in outcomes are small between the different grafts,” Steiner said. “Surgeons should be mindful of the patient’s desires and be able to perform ACL reconstruction with all of these different grafts.”
Cain noted the availability of multiple graft options also helps when an athlete has already experienced previous surgery or injury to the area.
“Someone may have already had a patella injury or may have had previous patella tendon surgery where you cannot use that graft,” Cain said. “You have to adapt and have some experience and confidence with several different graft types.”
“The main thing is for surgeons to have their own rationale for why they use certain grafts in certain people and be able to explain that, and hopefully back it up with data, so they can explain to the patients the benefits of each graft and potentially answer any questions the patients may have,” he added.
- Erickson BJ, et al. Arthroscopy. 2014;doi:10.1016/j.arthro.2014.02.034.
- Mall NA, et al. Am J Orthop. 2014;43:267-271.
- Mascarenhas R, et al. Arthroscopy. 2015;doi:10.1016/j.arhtro.2014.07.011.
- For more information:
- E. Lyle Cain Jr., MD, can be reached at the Andrews Sports Medicine and Orthopaedic Center, 805 St. Vincent’s Dr., Ste. 100, Birmingham, AL 35205; email: firstname.lastname@example.org.
- Brian J. Cole, MD, MBA, can be reached at Midwest Orthopedics at Rush, 1611 W. Harrison St., Chicago, IL 60612; email: email@example.com.
- Patrick C. McCulloch, MD, can be reached at Houston Methodist Hospital, Smith Tower, 6550 Fannin St., Houston, TX 77030; email: firstname.lastname@example.org.
- Brett D. Owens, MD, can be reached at Brown University Alpert Medical School, 222 Richmond St., Providence, RI 02903.
- Mark E. Steiner, MD, can be reached at New England Baptist Hospital, 125 Parker Hill Ave., Boston, MA 02120; email: email@example.com.
- A sports season does not go by without reports of ACL tears in athletes of all ages. Surgical reconstruction is the best alternative if they want to return to the same or near the same level of play. Despite increased interest in quadriceps tendon, hamstrings and allografts, bone-tendon-bone (BTB) probably remains the best option in this young, active age group. Regardless of the graft choice, the failure rate is higher in this active population compared with patients in the older than 25 years age group.
- In numerous studies, including two of our own, we demonstrated an increased failure rate of BTB allograft over BTB autograft in ACL reconstruction. More accurate tunnel placement has been analyzed recently. A more anatomic tunnel location in the ACL footprint is recommended. This brings its own set of problems with femoral tunnel shortening. Conversion to a two-incision approach, especially in revisions, can avoid some of these problems. Femoral tunnel can be drilled independent of tibial and remain anatomic. The athlete should be counseled as to the pros and cons of graft choices, anterior knee pain, later arthritis, sensation, failure rate and disease transmission.
- For the younger more active athlete, a BTB autograft with interference screw fixation would be my graft construct of choice. I would have no reservations in converting to a two-incision technique. Although the allograft is simpler with less morbidity, the BTB autograft has the best chance for long-term success and return to sport.
- Gene R. Barrett, MD, is an associate professor of orthopedic surgery in the Department of Orthopedic Surgery and Rehabilitation at the University of Mississippi Medical Center in Jackson, Miss.
- The literature is fairly clear on the advantages of autograft over allograft reconstruction of the ACL in young athletes. From a standpoint of early incorporation and lower risk of rerupture, this has been shown in two large multicenter studies in both primary and revision ACL reconstruction. The push toward allograft reconstruction previously has been because of the ability to eliminate donor site morbidity and have a more rapid early recovery.
- In my practice, we believe we can achieve rapid recovery and less donor site morbidity by using hamstring autografts. In comparison to BTB autograft, a hamstring typically provides more intra-articular graft volume and has incorporation rates similar to BTB. Our experience has been more rapid recovery and easier transition back into competition in our collegiate athlete population. Historically, the challenge with using hamstrings for ACL reconstruction was graft fixation methods. I believe these problems have been solved.
- My current technique involves both interference and suspensory fixation of a quadruple stranded graft. I do not use intra-articular sutures in the graft or fold it more than once. In revision cases, I still prefer autograft tissue and will harvest from contralateral extremity if necessary.
- A. Brent Bankston, MD, is the head team physician at Louisiana State University and associate professor of Louisiana State University Orthopedic Surgery, Baton Rouge, La