Analysis of the efficacy of arthroscopic allograft meniscus transplantation

  The meniscus is an important structure for maintaining knee function because it stabilizes the knee joint, absorbs shock, distributes stress, lubricates the joint, and improves cartilage nutrition. Therefore, the meniscus should be preserved and repaired as much as possible after an injury. However, not all meniscus injuries can be repaired. For example, meniscus free edge (white-white zone) injuries cannot be repaired due to lack of blood supply, and old meniscus injuries, severe degeneration or fragmentation are also difficult to repair. For such patients, meniscectomy is still the common treatment method. Although it can temporarily alleviate the symptoms and has good recent efficacy, it disrupts the mechanical balance of the knee joint, which may eventually lead to knee instability, cartilage degeneration and osteoarthritis [1-3]. To address this, some foreign scholars have attempted to perform allogeneic meniscal transplantation in meniscectomized patients, but there are few clinical studies on arthroscopy and meniscal healing after allogeneic meniscal transplantation [2,3]. We have performed arthroscopic minimally invasive allograft meniscus transplantation since 2006, and in this paper, we retrospectively analyzed the clinical data of these cases to discuss their short-term clinical outcomes and arthroscopic findings.
  Materials and Methods
  I. General information
  From January 2006 to July 2008, 21 patients (22 sides) who had meniscectomy after meniscal injury underwent allogeneic meniscal transplantation. Among them, 14 cases (15 sides) were male and 7 cases were female; age ranged from 19 to 49 years, with an average of 31.6 years. There were 16 cases of lateral meniscus injury (including disc meniscus injury) and 6 cases of medial meniscus injury. The interval from meniscectomy to allograft meniscus transplantation ranged from 0 to 9 years, with an average of 3.8 years. MR examination of the knee joint showed no articular cartilage lesion or osteoid formation in 12 cases, intercondylar spine osteophytes in 8 cases, and a small amount of osteoid formation at the edge of the tibial plateau in 1 case. The degree of articular cartilage damage was evaluated arthroscopically using a modified Outerbridge grading: grade 0 (normal articular cartilage) in 12 cases, grade I (with cartilage softening and swelling) in 5 cases, grade II (cartilage cracking or mild fragmentation to an extent of less than 0.5 inch/12.7 mm) in 3 cases, and grade III (cartilage rupture or exfoliation to an extent of more than 0.5 inch/12.7 mm) in 1 case.
  The indications for allogeneic meniscus transplantation are: patients aged 18 to 50 years, with meniscus removed or unpreserved, no serious articular cartilage and subchondral bone lesions, no obvious deformity of the femoral condyle or tibial plateau, no knee instability, abnormal lower limb force lines or abnormalities that can be corrected, no infection and other contraindications to surgical procedures.
  II. Surgical methods
  (A) Homogeneous meniscus preparation
  According to the National Food and Drug Administration executive standard GB/T19001 and medical device industry standard YY/T0287 specifications, and with reference to the American Association of Tissue Banks (AATB) principles [4], homogeneous meniscus donors were selected from legal donors aged less than 50 years (with all indicators meeting the national blood donor requirements). The meniscus was removed within 12 h (no more than 24 h under frozen conditions) of the cessation of blood supply, and the meniscus with the surrounding joint capsule and the attached proximal tibial bone was excised, rinsed under high pressure with distilled water, sealed in a sterile plastic bag, frozen at -80.C for 4 weeks (to reduce immunogenicity), and stored in a -30.C cold room. MRI imaging measurement software was used to measure the length and width dimensions of the recipient meniscus (Figure 1), expressed as the length of the ipsilateral tibial plateau in the coronal and sagittal planes. A donor meniscus with the same sex and side, comparable age, and dimensions 5%-15% larger than the recipient meniscus was selected. The donor meniscus was gradually thawed and sterilized by radiation irradiation (60Co, 25 kGy) to meet the national standards for in vivo implants.
  The donor meniscus was made into a graft with small 8mm diameter bone pins at the anterior and posterior horn stops (medial meniscus) or a preserved 8mm×8m bone bridge (lateral meniscus) on the operating table, and a non-absorbable traction wire was threaded at the anterior and posterior horn for backup (Figure 2).
  (B) Minimally invasive arthroscopic allograft meniscus graft surgery
  Continuous epidural anesthesia was used with a conventional arthroscopic surgical approach to the anterior medial and lateral aspects of the knee. Intra-articular exploration (Figure 3) is performed, and the meniscal stump is cleaned, preserving approximately 2 mm of meniscus peripheral tissue until punctate bleeding occurs. If necessary, the proximal stop of the lateral or medial collateral ligament is cut off from the femoral condyle to improve the arthroscopic view and fixed postoperatively with screws.
  1. Medial meniscus graft
  Arthroscopic fabrication of the posterior meniscal horn osteochannel: Using a knee arthroscopic positioner, a guide pin is drilled from the medial tibial tuberosity toward the center of the posterior meniscal horn stop, and a 9-mm hollow drill is used to create the osteochannel along the guide pin. To create the anterior meniscal tract: A guide pin is drilled through the medial arthroscopic incision into the center of the anterior meniscal horn stop, and a 9mm hollow drill is used to drill along the guide pin to create the blind canal. The guide pin is drilled with a locator from the medial tibial tuberosity into this blind canal and enlarged to 3 mm (Figure 4).
  The medial arthroscopic incision is enlarged to 1.8 cm, and the sutures of the anterior and posterior horn bone pins of the transplanted meniscus are led through this incision and the anterior and posterior horn bone channels to the medial tibial tuberosity with guide wires, and the meniscus is brought into the joint by tightening the sutures (Figure 5). The anterior and posterior horn bone pins are embedded in the anterior and posterior horn bone tracts, respectively. The meniscus was adjusted arthroscopically to its normal position, and the ends of the anterior and posterior horn traction sutures were tied and secured medially to the tibial tuberosity. The posterior horn of the meniscus was sutured with 2 stitches with a full internal suture, and the rest of the meniscus was sutured with about 6 stitches in an inside-out vertical manner, and the anterior horn could be sutured in an outside-in manner until the meniscus was securely fixed (Figure 6).
  2. Lateral meniscus graft
  Under arthroscopic surveillance, a 9-mm wide bone chisel is used to create a bone groove from the anterior meniscus stop through the lateral intercondylar spine to the posterior meniscus stop with a cross-section of 9 mm × 9 mm. Using a knee arthroscopic positioner, the anterior and posterior meniscus bone channels are created in the bone groove at the center of the anterior and posterior meniscus stops with a diameter of approximately 3 mm. The anterior and posterior horn sutures are led through the anterior and posterior horn tracts, and the meniscus is brought into the joint. The bone bridge connecting the anterior and posterior horn of the meniscus was embedded in the bone groove, and the meniscus was adjusted to its normal position under arthroscopy.
  (C) Postoperative treatment
  In the first week after surgery, the affected limb was fixed with a knee brace in the straightened 0. On the second day after surgery, the isometric contraction exercises of the quadriceps muscle were started, avoiding weight bearing on the affected limb. 1 week later, knee mobility exercises were performed under the protection of the brace. At 3 weeks postoperatively, the knee joint was fully extended and flexion was limited to 60. At 6 weeks postoperatively, the knee joint was fully extended and the flexion mobility was gradually approaching 90 at a rate of about 10. per week. At 12 weeks postoperatively, the knee flexion mobility approached 120, and weight-bearing exercises were gradually started on the affected limb. At 24 weeks postoperatively, the knee mobility should be normal, and normal walking with the protective brace removed and water exercises should be practiced, but prolonged squatting, jumping and rapid directional movements should be avoided. At 36 weeks after surgery, light physical exercise such as running and cycling should be started. At 48 weeks after surgery, resume all sports.
  Follow-up methods and evaluation indexes
  Knee function before and after surgery was evaluated by VAS pain score, Lysholm score and IKDC grading. MRI evaluation criteria of the meniscus were based on the method of Mink and Fischer [5,6]: grade 0 was a homogeneous low-signal shadow of the normal meniscus; grade I injury was a spherical or irregular dot-like high-signal shadow that did not extend to the joint surface; grade II injury was a horizontal line-like high-signal shadow that did not extend to the joint surface and could extend to the joint capsule junction of the meniscus; grade III injury was an abnormal high-signal shadow that extended to the joint surface of the meniscus; grade IV injury was an abnormal high-signal shadow that extended to the joint surface of the meniscus. Grade III injury is an abnormal high-signal shadow extending to the meniscus surface; Grade IV injury is a change in the shape of the meniscus or a fragmentation of the meniscus.
  MRI evaluation of articular cartilage injury is based on Recht’s criteria [7]: grade 0, normal articular cartilage, or diffuse homogeneous thinning of cartilage, but smooth surface; grade I, loss of cartilage layering structure, limited low signal areas within the cartilage, smooth cartilage surface; grade II, mild to moderate irregularity of cartilage surface contour, depth of cartilage defect does not reach 50% of the full thickness; grade III, severe cartilage surface contour Grade III, severe irregularity of cartilage surface contour, the depth of cartilage defect reached more than 50% of the full thickness, and complete exfoliation was not seen; Grade IV, the full layer of cartilage was exfoliated, defective, and subchondral bone was exposed.
  V. Statistical analysis
  SPSS 12.0 statistical software (SPSS Inc.) was used to compare patients’ preoperative and follow-up joint mobility, VAS pain score, and Lysholm score using paired design data t-test with a test level of 0.05 in both directions. rank sum test and X2 test were used to compare IKDC and cartilage damage grading with a test level of 0.05 in both directions.
  Results
  All cases in this group were followed up for 6 to 28 months, with an average of 16.3 months. No surgical side effects occurred, and no infections or meniscus removal were required. There were no abnormal postoperative immunological indexes and no obvious allogeneic tissue immune rejection.
  I. Knee function
  Knee mobility was fully extended before surgery, and the postoperative knee extension was comparable to the preoperative level. Flexion mobility ranged from 105 to 150. preoperatively (mean 121.4.) and 120 to 150. at the last follow-up (mean 132.7.), with no statistically significant difference (t = 1.123, P = 0.268). Among them, two patients neglected rehabilitation exercises after surgery, and the knee flexion mobility (120°, 120°) did not reach the preoperative level (135°, 150°) during the follow-up period. one patient had limited knee flexion before surgery (105°), and the flexion mobility improved after surgery (135°) with rehabilitation training. The results of VAS knee pain score, Lysholm score and IKDC classification are shown in Table 1.
  Table 1 Results of functional evaluation of the knee joint in this group of cases
  Time
  VAS pain score (points)
  Lysholm score (points)
  IKDC grading
  A
  B
  C
  D
  Preoperative
  7.0 ± 2.3
  64.3 ± 15.7
  3
  11
  7
  Final follow-up
  3.2 ± 1.3
  80.1 ± 19.4
  6
  10
  3
  2
  Statistical value
  t = 6.591
  P = 0.000
  t = 2.687
  P= 0.011
  Hc = 21.159
  P = 0.0003
  II. MRI performance
  All patients in this group underwent MR examination before surgery, and all MRI images showed grade III or higher meniscal injury signal shadow. In 13 cases, one case had grade I and II injury signal in the anterior horn of the meniscus and two cases had grade II injury signal in the posterior horn of the meniscus, but there were no clinical symptoms. The rest were in good shape, but had internal signal heterogeneity (Figure 8). 6 cases of preoperative articular cartilage grade 0, 4 cases of grade I, 2 cases of grade II, and 1 case of grade III were examined by MR in 13 patients; 5 cases of grade 0, 4 cases of grade I, 3 cases of grade II, and 1 case of grade III were examined 1 year after surgery. The difference between preoperative and postoperative was not statistically significant (Hc = 0.570, P = 0.966).
  III. Arthroscopic examination
  In one case of this group, arthroscopic examination was performed 3 months after medial meniscus transplantation, and it could be observed that the edge of the transplanted meniscus was basically healed with the joint capsule, and the surrounding synovial membrane was congested; the meniscus was morphologically intact, with sharp edges, but slightly less stable and brittle in texture (a scratch could be formed by normal examination with a blunt-tipped probe) (Figure 9a). The articular cartilage evaluation was Outerbridge grade II both before and after surgery.
  In one case, arthroscopic examination was performed 9 months after lateral meniscal transplantation, and it was observed that the transplanted meniscus healed well with the joint capsule and the anterior and posterior angles healed firmly; the meniscus was morphologically intact, with a hard texture and slightly blunt edges (Figure 9b). The articular cartilage evaluation was Outerbridge grade I before and after surgery.
  Arthroscopic examination was performed in one case 18 months after lateral meniscal transplantation, and it was observed that the transplanted meniscus healed firmly with the joint capsule, with good morphology and appearance and texture similar to a normal meniscus. The edges of the meniscus were slightly ragged and were slightly trimmed under arthroscopy (Figure 9c). The articular cartilage was evaluated as Outerbridge grade 0, the same as preoperatively.
  DISCUSSION
  I. Acquisition and preservation of the homogeneous meniscus
  Preservation techniques for homogeneous meniscus after acquisition include four methods: fresh preservation, cryopreservation, deep cryopreservation, and freeze-drying. Fresh meniscus can maintain cellular activity [2], but all cells will be replaced by recipient cells after meniscus transplantation [3], losing its superiority. In addition, fresh meniscus is highly antigenic, has a short preservation time, has a high risk of transmitting disease, and is now largely unused due to difficulties in donor discovery and size matching [1, 3]. Freeze-drying methods can destroy the original structural components of the meniscus, causing tightening and matrix degeneration, so they are also not recommended. Cryogenic freezing and deep cryopreservation are two commonly used methods, among which the clinical application results after cryogenic frozen meniscus transplantation are close to those of normal knee [3]. Through this group of cases, we believe that the cryopreservation method better maintains the morphological characteristics of the meniscus, is simple and inexpensive to operate, and is recommended for domestic allogeneic meniscus tissue banks.
  II. Surgical technique of allogeneic meniscus transplantation
  Allogeneic meniscus transplantation can be performed by incisional surgery, arthroscopic-assisted and total arthroscopic minimally invasive surgery. The minimally invasive total arthroscopic surgery technique is less invasive and facilitates rehabilitation exercises and functional recovery. The key steps are as follows.
  (i) Selecting a homogeneous allograft meniscus of matching size
  The size of the required meniscus can be determined by measuring the size of the donor and recipient tibial plateau by X-ray, CT or MRI. Previously, the size of the transplanted meniscus was determined based on the contralateral normal meniscus, but Johnson et al [8] showed that there is a difference in the size of the meniscus between the two sides of the knee in humans.McDermott et al [9] demonstrated that there is little error in determining the size of the meniscus by measurement of the ipsilateral tibial plateau.Shaffer et al [10] demonstrated that the size of the meniscus can be determined more accurately by MRI than by X-ray. accurate. In our case, computerized MRI imaging software was used to measure the size of the affected tibial plateau as a basis for selecting the size of the homogeneous meniscus. Considering that a certain degree of wrinkling of the allogeneic meniscus will occur after transplantation, it is recommended to select an allogeneic meniscus that is 5% to 15% larger than the size of the recipient [3].
  (ii) Proper treatment of the original meniscus stump
  The meniscal stump should be excised until punctate hemorrhage appears on the synovial rim of the meniscus, and a small amount (about 2 mm) of the meniscal rim should be preserved to keep the joint capsule intact and to preserve as much as possible stable structures such as the coronary ligament of the original meniscus. Slightly poorer meniscus stability was observed during arthroscopic reexamination in three cases in our group. Instability of the transplanted meniscus with outward migration or herniation out of the joint space has also been reported in foreign literature [1, 3]. Therefore, we recommend that the stable structures of the meniscus edges should be preserved as much as possible intraoperatively.
  (iii) Precise fixation of the anterior and posterior meniscus angles
  The commonly used way of positioning the anterior and posterior meniscus angles is based on the center of the anterior and posterior meniscus angle stops [1, 3]. The methods of fixation of the anterior and posterior meniscus angles can be divided into two types of fixation: preservation of the anterior and posterior angular stops with bone pins (bone bridges) and suturing of the anterior and posterior angles. Some studies have confirmed that the fixation method with preserved bone pins (bone bridges) is closer to the physiological state [3, 11], so this method was used in all cases in this group. The anterior and posterior angular distances of the lateral meniscus are short, and the bone bridge fixation method is usually used to make the anterior and posterior angular distances more precise, while the anterior and posterior angular distances of the medial meniscus are longer, and the bone peg fixation method is usually used.
  (iv) Tight suture of meniscus and joint capsule
  The suture between the transplanted meniscus and the joint capsule is generally performed by an inside-out suture technique. We recommend the use of vertical sutures, as they are more conducive to a tighter alignment of the meniscus to the capsule than horizontal sutures. We also recommend alternating the use of femoral and tibial facet sutures for a better fit of the meniscus to the tibial plateau.
  Postoperative management of allogeneic meniscus transplantation
  The rehabilitation process after meniscus transplantation has many problems that have not been determined, among which joint mobility forging is one of the main challenges. Because the meniscus will move back and forth during knee flexion and extension activities, which may have adverse effects on the healing of the transplanted meniscus. In our case, the range of knee motion was limited to 0° of extension and 60° of flexion for 3 weeks after surgery (especially for the lateral meniscus graft) because the meniscus hardly moved during this range of knee motion. The range of motion of the knee can be unrestricted for 3 months after surgery.
  Regarding the duration of postoperative weight-bearing, some authors suggest that early weight-bearing is possible in 1 to 3 weeks [12], whereas we believe that a relatively conservative rehabilitation program is more desirable. As observed in the arthroscopic reexamination of our cases, although the meniscus and joint capsule were basically healed at 3 months after surgery, the meniscus was fragile, slightly less stable, and easily damaged. Therefore, premature weight bearing may lead to damage or degeneration of the transplanted meniscus. Adverse consequences of early postoperative weight-bearing on the meniscus have also been reported in the literature [13]. Therefore, we recommend that joint mobility exercises be performed mainly under non-weight-bearing or assisted weight-bearing conditions for 6 to 12 weeks after surgery.
  IV. Results and problems of allogeneic meniscus transplantation
  The recent clinical results of our cases were satisfactory, and the patients’ pain symptoms and joint function evaluation indexes were improved. Postoperative arthroscopic examination showed that the transplanted meniscus was viable, morphologically intact, and healed well with the surrounding tissues. The results of foreign experimental studies also suggest that the recipient synovial cells may migrate into the transplanted meniscus after allogeneic meniscus transplantation, replacing the original meniscus chondrocytes and reconstructing the cartilage matrix. Capillaries from the synovial membrane of the joint capsule allow the grafted meniscus to complete the process of recanalization, and the grafted meniscus can replace most of the functions of the original meniscus [14].
  MRI 1 year after surgery in our cases showed signal heterogeneity within the grafted meniscus, and in some cases there was a degree I or II damage signal; postoperative arthroscopy also suggested that the grafted meniscus was more brittle and easily damaged in the early stage. It is speculated that this situation may be related to the process of internal structural reconstruction after meniscus transplantation, i.e. before the process of reconstructing cartilage matrix in the transplanted meniscus is completed, the texture of the meniscus is more fragile and easy to be damaged. This is supported by the observation that the appearance and texture of the transplanted meniscus gradually approximated that of a normal meniscus during the arthroscopic examination 18 months after surgery.
  Although allogeneic meniscus transplantation has been shown to be viable and morphologically intact, there is uncertainty regarding the protective effect of the transplanted meniscus on articular cartilage [15-17]. Some authors believe that allogeneic meniscus transplantation has a protective effect on articular cartilage [2], while others hold the opposite opinion [16]. Arthroscopic examination 18 months after meniscal transplantation in our case did not reveal any articular cartilage damage, but it was not enough to prove that allogeneic meniscal transplantation has a long-term protective effect on articular cartilage.
  As with other allogeneic transplants, allogeneic meniscal transplants involve immune rejection. However, the meniscus has a small cellular component and no blood supply to most areas, making it a relatively non-immunogenic organ that is shielded from immune reactions. However, small amounts of chondrocytes and collagen in the meniscus can still express antigens and trigger an immune response. It is now accepted that an immune response may be present in allogeneic meniscus transplants, but not enough to produce significant adverse effects and rejection of the transplanted meniscus [14]. In our group of cases, no significant immune rejection was observed, but postoperative arthroscopic reexamination observed significant synovial congestion, short-term synovial inflammatory reaction and joint effusion in some patients, which may be related to a mild immune reaction triggered by allogeneic meniscus transplantation [1,16].
  The results of our cases showed that allogeneic meniscus transplantation could relieve pain and improve function to some extent, and the transplanted meniscus could survive. However, there are still many problems regarding the stability reconstruction and postoperative rehabilitation of the transplanted meniscus [18], and the protective effect of the transplanted meniscus on articular cartilage needs longer-term follow-up studies. Currently, allogeneic meniscus transplantation has not become a standard treatment technique in China, but given the great difficulties in the prevention and treatment of postmeniscectomy complications, this technique could potentially be an option for the relief of osteoarthritis symptoms after meniscectomy [14, 18].