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Meniscal Allograft Transplantation Abstract Meniscal allograft transplantation is a reasonable treatment option for the young patient with symptomatic meniscal deficiency. Although clinical results are promising, in most studies only mixed procedures have been performed, with short- or medium-term follow-up. Important potential prognostic factors include patient selection, severity of degenerative changes, limb stability and alignment, graft sizing and processing methods, graft placement, and graft fixation. The use of meniscal allograft transplantation should be considered a salvage operation for the difficult clinical dilemma of meniscal deficiency in young patients. Nonetheless, in carefully selected patients, this procedure can predictably relieve compartmental symptoms, and, in conjunction with anterior cruciate ligament reconstruction, restore knee stability. In addition, the partial restoration of meniscal function provided by this procedure may slow the degenerative arthritic process. I njury to the menisci of the knee can lead to alteration in the stabil- ity and biomechanics of involved joints. Meniscal injuries may alter the transmission of loads across the knee joint or may destabilize the knee, especially when injuries are sustained in conjunction with ante- rior cruciate ligament (ACL) injury. Such injuries may lead to clinical and radiographic articular cartilage changes. Meniscus repair or partial meniscectomy are common proce- dures that attempt to preserve me- niscal functions, which include load transmission, proprioception, joint lubrication, and stability. However, with large tears that require partial or total meniscal excision, preserva- tion of the meniscus sometimes is impossible. Meniscal deficiency may in turn lead to progressive dete- rioration of the articular cartilage, with resultant radiographic joint space narrowing. Meniscal allograft transplanta- tion is a surgical option for select pa- tients with symptomatic meniscal deficiency. Often this deficiency is addressed in conjunction with con- comitant injuries, the most common being tears of the ACL. A number of basic science as well as clinical stud- ies have helped clarify the role of the variables that may contribute to suc- cessful meniscal transplantation. These factors include patient selec- tion, surgical technique, graft sizing and preservation, graft fixation, and graft placement. Anatomy and Function The menisci are fibrocartilaginous structures consisting of coarse carti- lage bundles circumferentially ar- ranged to disperse compressive load and radially resist shear. 1 Water ac- counts for 70% of meniscal compo- sition; collagen (90% of it type I) Jon K. Sekiya, MD Christopher I. Ellingson, MD Dr. Sekiya is Assistant Professor, University of Pittsburgh Medical Center, Center for Sports Medicine, Pittsburgh, PA. Dr. Ellingson is Lieutenant Commander, Medical Corps, United States Navy, Bone and Joint/Sports Medicine Institute, Department of Orthopaedic Surgery, Naval Medical Center Portsmouth, Portsmouth, VA. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. None of the following authors or the departments with which they are affiliated has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Sekiya and Dr. Ellingson. Reprint requests: Dr. Sekiya, University of Pittsburgh Medical Center, Center for Sports Medicine, 3200 S Water Street, Pittsburgh, PA 15203. J Am Acad Orthop Surg 2006;14:164- 17 4 Copyright 2006 by the American Academy of Orthopaedic Surgeons. 164 Journal of the American Academy of Orthopaedic Surgeons makes up 60% to 70% of the dry weight. 2 Trapped by negatively charged glycosaminoglycans, water in the menisci provides resistance to compressive loads, and two types of fibrochondrocytes synthesize the fi- brocartilaginous matrix. At birth, the entire meniscus is vascular, but by adulthood, only the outer 10% to 30% of vascularity remains, with blood supplied via the perimeniscal capillary plexus off the superior and inferior medial and lateral genicular arteries. 3,4 Postulated to have mech- anoreceptive proprioceptive func- tion, 5 type I and II nerve endings are found at the horn insertions in the outer portions. Both menisci are C-shaped and at- tach to the tibia via bony attach- ments to the tibial plateau; a discoid variant of the lateral meniscus is found in 3.5% to 5% of patients. 6 The surface area of the anterior tib- ial bony attachment of the medial meniscus is 61 mm 2 ; the posterior attachment is anterior to the inser- tion of the posterior cruciate liga- ment. 7 Covering a larger portion of the tibial articular surface, the later- al meniscus is semicircular, with the anterior horn attaching adjacent to the ACL and the posterior horn at- taching behind the intracondylar eminence. 3 With knee flexion, aver- age excursions of the menisci are 5.2 mm for the medial and 11 mm for the lateral. 8 A primary function of the menisci is load sharing, which is accom- plished through improving knee con- gruency and increasing joint contact area. The medial and lateral menisci transmit 50% and 70% of their com- partmental loads, respectively. Me- dial meniscectomy decreases contact area 50% to 70% and increases con- tact stress 100%, 3 whereas lateral meniscectomy decreases contact area 40% to 50% but dramatically in- creases contact stress 200% to 300% secondary to the relative convex sur- face of the medial tibial plateau. 3 Another function of the menisci involves their viscoelastic proper- ties, which aid in shock absorption; meniscectomy has been reported to decrease the shock absorption capa- bilities of the knee by 20%. 9 The medial meniscus also acts as a sec- ondary restraint to anterior tibial translation in the ACL-deficient knee; therefore, medial meniscecto- my in the ACL-deficient knee in- creases tibial translation by 58% at 90°. 3 The posterior horn of the medi- al meniscus is especially important in contributing to joint stability. 10 Meniscal Allograft Preservation The four main methods of pre- serving allografts are fresh, cryopre- served, fresh-frozen (deep-frozen), and freeze-dried. In accordance with standards established by The Amer- ican Association of T issue Banks for donor suitability and testing, 11 me- nisci are harvested under strict asep- tic conditions within 12 hours of cold ischemic time. They may be harvested with or without bone plugs and a small synovial rim for atraumatic handling of the al- lograft. 11 The allografts are then pro- cessed according to the preservation method. Fresh grafts, maintained at 4°C in lactated Ringer solution, can be stored for up to 7 days only. Such limited time for graft sizing and se- rologic testing presents logistical dif- ficulties and limits the use of fresh grafts in clinical practice. Further, these grafts have not been shown to improve efficacy in vivo. Cryopreserved allografts main- tain a cell viability of 10% to 40% by use of controlled freezing in a glycerol-containing medium (ie, cryoprotectant). The expense and difficulty of this technique has lim- ited its use, especially given the un- certainty of donor-cell viability. Me- niscal allografts are invaded by host cells as early as 4 weeks after trans- plantation. 12 Fresh-frozen allograft preserva- tion, in which allografts are stored at approximately −80°C, is a simpler and less expensive method than cryopreservation. Although fresh- frozen allografts lack donor-cell via- bility, the lack of viability has not af- fected allograft survival and meniscal transplant outcomes. The use and demand for fresh-frozen me- niscal allografts is increasing. Freeze-drying (lyophilization) in- volves the dehydration of allografts during freezing in a vacuum. The al- lografts are then thawed and rehy- drated before transplantation. Al- though this method allows for indefinite storage, it also produces alterations in the biomechanical properties and the size of the al- lografts. Today, freeze-drying has fallen out of use and is not recom- mended. Means for secondary sterilization of allografts are available but also are not recommended; two examples are ethylene oxide and gamma ir radia- tion. The use of ethylene oxide has been linked to soft-tissue synovitis caused by its by-products. 13 Expo- sure to >2.5 mRad of gamma radia- tion negatively affects the mechani- cal properties of collagen-containing tissues. 14 Because >3 mRad of gam- ma irradiation is needed to eliminate human immunodeficiency virus DNA in allograft tissue, the use of gamma irradiation in the steriliza- tion of meniscal allografts is not rec- ommended. In addition, according to one series, 15 poor clinical results may be associated with gamma irra- diation of the meniscal allograft. Meniscal allografts are not type cross-matched with the recipient; 16 therefore, occasionally an immune system inflammatory response oc- curs. An immunologic study by Ro- deo et al 17 identified class I and II hu- man leukocyte antigens on frozen meniscal allografts. The authors evaluated 28 meniscal allografts (25 patients); all were deep frozen and nonirradiated. Nine of ten samples that underwent immunohistochem- ical analysis contained immunoreac- tive cells, but no frank evidence of immunologic rejection was seen. In Jon K. Sekiya, MD, and Christopher I. Ellingson, MD Volume 14, Number 3, March 2006 165 general, although histology scoring was improved in menisci with no immune response, there was no dif- ference in clinical outcome between the two groups. However, the effect of an immune system inflammatory response is clinically unknown. A prospective study to evaluate the re- lationship between inflammatory re- sponse and meniscal allograft rejec- tion or function is warranted. 16 Preclinical Evidence of Meniscal Allograft Healing Function In vitro and animal model studies have advanced the understanding of meniscal function, allograft selec- tion, and the technical consider- ations of meniscal transplantation. In 14 cryopreserved medial meniscal allografts performed in a canine model, Arnoczky et al 18 showed that grafts healed to the capsule by fi- brovascular scar and retained their normal gross appearance. Histologic examination at 3 months revealed cellular distribution and metabolic activity comparable with those of controls. Medial meniscal transplantation using autograft, fresh allograft, or cryopreserved allograft were com- pared in a goat model. 19 Evaluation at 6 months revealed little histolog- ic difference between implanted me- nisci and controls. In addition, the allografts had nearly normal periph- eral vascularity, although transplant- ed menisci were reported to have slightly decreased proteoglycan con- tent with increased water content. In another study, the use of a vascu- larized synovial flap accelerated re- vascularization of allograft menisci in rabbits. 20 No significant difference was found between cryopreserved and fresh-frozen allografts in goats, with nearly complete remodeling of both types of allografts at 6 and 12 months. 21 Using DNA analysis, Debeer et al 22 reported the nearly complete re- population of cryopreserved menis- cal allograft tissue by host cells in al- lograft remodeling in a human recipient 1 year after transplanta- tion. A cadaveric biomechanical study on meniscal allografts demonstrated improved contact areas and de- creased contact pressures after later- al meniscus allograft replacement. 23 This study demonstrated the impor- tance of securing both the anterior and posterior horns of meniscal al- lografts. With both horns released, contact pressures with allografts were equal to contact pressures in knees after total meniscectomy. Huang et al 24 recently reinforced findings that show improved contact pressures in meniscectomized knees after meniscal transplantation. However, the efficacy of meniscal transplantation in slowing degener- ative changes has not consistently been demonstrated. In a study of a rabbit model reported by Cummins et al, 25 transplants performed imme- diately or at 3 months after medial meniscectomy showed a slowing in the progression of degenerative changes. Regardless of the timing of transplantation, groups receiving a transplant had fewer degenerative changes compared with meniscecto- mized controls. Yet Aagaard et al 26 showed improved prevention of ar- ticular cartilage degeneration in sheep with meniscal allograft trans- plants performed immediately com- pared with 3 months after meniscec- tomy. However, Rijk et al 27 found no significant difference with reference to subsequent degeneration between meniscectomized rabbit knees and those undergoing immediate or de- layed (6 weeks) meniscal transplan- tation. Similarly, using a sheep mod- el, Edwards et al 28 found no difference among total meniscecto- my, meniscal autograft, or meniscal allograft groups with respect to de- generative changes seen at an aver- age of 21 months postoperatively. In another study, Rijk and Van Noorden 29 showed significantly (P ≤ 0.005) more shrinkage in meniscal allografts implanted 6 weeks after meniscectomy compared with those implanted immediately after menis- cectomy in a rabbit model. Interest- ingly, the cellular content and his- tology of implanted menisci did not differ significantly between the two groups. Experimental and clinical studies are needed to evaluate the ef- fect that shrinkage may have on long-term meniscal allograft proper- ties and function. Indications and Preoperative Evaluation Surgery for the meniscus- deficient knee should be considered only after exhausting all nonsurgical measures. Nonsurgical treatment of patients who have undergone menis- cectomy includes using unloading braces, encouraging nonimpact ac- tivities and exercises, and initiating pharmacologic measures. When these therapies fail to provide relief of symptoms or to prevent pro- gression of joint space narrowing, meniscal transplantation may be considered in select patients. The exception to nonsurgical therapy may be concomitant ACL and medial meniscus deficiency with significant anteromedial rotatory instability. In this situation, earlier intervention of an ACL combined with medial meniscal transplanta- tion may improve stability, ACL graft survival, and eventual clinical outcome. 10,30-33 Meniscal transplantation is indi- cated in patients aged <40 years with an absent or nonfunctioning menis- cus. The upper limit is 50 years for patients who are highly active with only limited arthritis and who are not good candidates for arthroplasty. These patients have pain localized to the affected compartment with activ- ities of daily living or sports, normal mechanical alignment, and Outer- bridge grade I or II articular changes. Contraindications include knee in- stability or marked varus/valgus malalignment, unless these issues can be addressed concurrently. Varus/valgus malalignment is de- Meniscal Allograft Transplantation 166 Journal of the American Academy of Orthopaedic Surgeons fined as asymmetry ≥2° to 4° com- pared with the contralateral knee or as the weight-bearing line on long-leg alignment radiographs falling into the affected meniscus-deficient com- partment. Additional contraindica- tions to meniscal transplantation are age >50 years, osteophytes indicating bony architectural changes, or Out- erbridge grade IV articular changes (unless focal defects are addressed concomitantly with osteochondral allograft transplantation or autolo- gous chondrocyte implantation). Preoperative physical examina- tion should include inspection of stance, gait, and squat and of prior incisions about the knee. Examina- tion includes joint-line palpation, McMurray’s test, knee range of mo- tion, presence of effusion, muscle strength, and assessment of ligamen- tous instability. Radiographic stud- ies include weight-bearing 45° flex- ion posteroanterior, Merchant, and non–weight-bearing lateral views us- ing magnification markers. Long-leg alignment radiographs also should be obtained in order to objectively evaluate lower extremity mechani- cal alignment. Magnetic resonance imaging (MRI) provides information regarding the subchondral bone, me- nisci, and hyaline cartilage. When previous arthroscopic images are un- clear or are not available, diagnostic arthroscopy can accurately define the extent of meniscectomy and de- gree of arthrosis. Although sizing and matching of meniscal allografts to recipient knees is critical, the tolerance of size mismatch in knees undergoing me- niscal transplantation is not known. Sizing of allografts is done using MRI, computed tomography, or plain radiographs, or by making di- rect measurements. In patients with a prior meniscectomy, the contralat- eral knee may be used for sizing. In a study measuring patient knees, however, Johnson et al 34 reported variability in meniscal size between opposite knees. The consistent rela- tionship between meniscal size and landmarks in plain radiographs re- ported by Pollard et al 35 often is used by tissue banks for allograft sizing. Although comparison of MRI scans to plain radiographs showed that MRI is slightly more accurate at siz- ing allografts, only 35% of menisci measured with MRI came to within 2 mm of the actual size. 36 Carpenter et al 37 compared MRI scans with computed tomography scans and plain radiographs for me- niscal allograft sizing and found that MRI consistently underestimated the anteroposterior and mediolateral sizes of both the medial and lateral menisci; however, MRI was more ac- curate in estimating meniscal height. The authors concluded that com- puted tomography and plain radiog- raphy are more useful in allograft siz- ing but that MRI measurements may improve as experience is gained. McDermott et al 38 measured the menisci in 22 pairs of cadaveric knees and found that the average medial and lateral meniscal lengths were 45.7 mm and 35.7 mm, respec- tively. Additionally, the authors measured the meniscal circumfer- ence, meniscal body width, and overall meniscal width, then corre- lated these measurements with ra- diographic sizing of the tibial pla- teaus. By using measurements of the length and width of the medial and lateral tibial plateaus, meniscal size was predicted with a mean error rate of 5%. 38 Huang et al 39 evaluated the cross- sectional parameters of lateral me- niscal allografts compared with na- tive lateral menisci in cadaveric knees and found increased contact pressures when allografts did not match native menisci. The greatest predictor of differences in contact pressures was the difference found in the width of the menisci. The au- thors therefore postulated that pro- tocols used to select allografts should focus on cross-sectional pa- rameters to match the native menis- cus, particularly width. Surgical Technique Isolated Meniscal Transplant Surgical Technique Garrett 40 initially used an open technique for medial meniscal trans- plantation, with takedown of the medial collateral ligament with a piece of bone off the medial femur. The graft was placed under direct vi- sualization, and subsequent repair of the medial collateral ligament was performed with a screw and washer. This technique is no longer used be- cause of the amount of soft-tissue trauma that occures to the medial stabilizing structures of the knee. Once the patient is anesthetized, meniscal allograft transplantation begins with an examination to eval- uate range of motion and ligamen- tous instability. 31,41-43 Meniscal defi- ciency and the condition of the articular cartilage are determined ar- throscopically. The involved menis- cus posterior horn and body are débrided to a 1- to 2-mm synovial rim, leaving a vascular source to aid in graft healing. Graft passage and fixation are achieved through a small medial or lateral parapatellar arthrotomy as well as an accessory posteromedial arthrotomy or pos- terolateral incision (for medial or lat- eral meniscal transplantation, re- spectively) (Figure 1). Lateral meniscus grafts are fashioned with a bone bridge, whereas medial grafts are fashioned with bone plugs (Fig- ure 2). Fixation of both horns is crit- ical for proper function 23 and can be accomplished through a two-bone plug technique, 44 through a bone bridge in a trough 41,42,45 keyhole for the lateral meniscus, with no bone block, 23,46,47 or with suture fixa- tion. 48 For a medial transplantation, the anterior and posterior bone plugs are pulled into their respective tunnels placed at the native meniscal inser- tion sites. For a lateral transplanta- tion, the bone bridge is placed into a bone trough at the anatomic posi- Jon K. Sekiya, MD, and Christopher I. Ellingson, MD Volume 14, Number 3, March 2006 167 tions of the anterior and posterior horns of the lateral meniscus. With either technique, the bone fixation is secured using a no. 2 braided suture. Anatomic placement of meniscal al- lografts is essential for proper distri- bution of contact pressures. Sekaran et al 49 found that nonanatomic place- ment of medial meniscus posterior horn tunnels ≥5 mm medially and ≥5 mm posteriorly caused a notable shift in the centroid of contact pres- sure and increased contact pressures. Allograft fixation is then achieved by suturing to the native meniscus rim with an inside-out technique, starting at the posterolateral or pos- teromedial corner to the midbody to establish position and fit. A no. 2-0 braided polyester suture on long nee- dles can be used for the inside-out ar- throscopic technique. The anterior to midbody meniscal allograft rim is fixed using a no. 0 Ethibond (Ethi- con, Somerville, NJ) suture placed through the parapatellar arthrotomy. A femoral distractor on the affected knee compartment can assist with graft passage, arthroscopic visualiza- tion (especially of the posterior horn), and graft fixation (Figure 3). Additional techniques for lateral meniscal allograft transplantation include modifications to the bone- bridge-and-trough technique that ac- tually lock in the lateral meniscal al- lograft, thereby providing additional stability to the meniscal horn fixa- tion. One popular method includes the keyhole technique, 50 which uses a guide and drill to create a round bone trough that then narrows at the surface of the tibial plateau (Figure 4). This allows the bone bridge to Figure 2 Medial meniscal allograft fashioned with bone plugs attached to the anterior (white arrow) and posterior (black arrow) horns. Preplaced sutures are fixed to the posterior horn of the medial meniscal allograft (arrowhead). ACL = anterior cruciate ligament Figure 3 A femoral distractor can assist with graft passage, posterior horn visualization, and suture fixation. Figure 1 A, Medial meniscal allograft transplantation with anterior (large arrow) and posterior (small arrow) bone plugs through transosseous tunnels. A combination of arthroscopically and open placed sutures fix the meniscal allograft to the peripheral rim. B, Lateral meniscal allograft transplantation using a bone bridge. The bone bridge is secured in the tibial trough (large arrow) using transosseous sutures (small arrow). A combination of arthroscopically and open placed sutures fix the meniscal allograft to the peripheral rim. Meniscal Allograft Transplantation 168 Journal of the American Academy of Orthopaedic Surgeons lock into the tibial bone trough, pro- viding additional stability to the construct. Other similar methods exist, including the “dovetail” tech- nique. Although suture fixation at- tached to bone plugs or a bone bridge is usually sufficient for a secure graft healing, clinically these techniques offer additional methods for menis- cal horn fixation stability. Others have recommended suture attachment without bone for menis- cal allograft anterior and posterior horn fixation. 48 This technique uses a circumferential osseocancellous trough combined with transosseous tibial tunnel fixation of the meniscal allograft horns (Figure 5). Recently, the popularity of the bone-bridge-and-trough technique has been expanded for use in medial meniscal allografts. Preserving the circumferential hoop stresses and se- cure fixation of the anterior and pos- terior horns of the meniscal allograft are attractive reasons for using this technique; however, we caution against its use because of the poten- tial for problems resulting from the position of the medial meniscus pos- terior horn, which is directly in line behind the ACL tibial attachment 34 (Figure 6). To position this trough without disrupting the ACL attach- ment, the tendency may be to medi- alize the bone trough location, there- by altering movement of the anatomic location of the posterior and/or anterior horn attachments. This nonanatomic positioning may then significantly alter the biome- chanical properties of the transplant- ed meniscus. 49 However, this may not be a serious issue in the patient undergoing a combined medial me- niscus transplant and ACL recon- struction, which allows the ACL tunnel to be drilled following ana- tomic bone bridge placement. Combined Meniscal Transplantation With Anterior Cruciate Ligament Reconstruction Meniscal transplantation com- bined with ACL reconstruction is performed in knees with ACL insuf- ficiency and symptomatic meniscal deficiency. Standard femoral and tib- ial tunnels are drilled and prepared before meniscal allograft insertion, and the procedure is performed as previously described. 30,31,41,42 The use of patellar tendon allograft decreases associated donor-site morbidity in this complex knee reconstruction. T ibial tunnel drilling requires special care because this tunnel often en- croaches on the bone trough for the meniscus. 41 To circumvent this prob- lem, the ACL graft passage and fem- oral fixation should be done before placing the lateral meniscal allograft Figure 4 Keyhole technique for lateral meniscal allograft transplantation. A, Lateral meniscal allograft fashioned using the keyhole technique. Note that the deeper portion of the bone bridge (large arrow) for the meniscal allograft is fashioned larger than the superficial portion (small arrow), which is matched to the corresponding recipient in the lateral tibia (B). This allows the lateral meniscal allograft to “lock” into the tibial attachment. (Panel A adapted with permission from Cryolife, Marietta, GA.) Figure 5 Osseocancellous trough technique for meniscal allograft fixation. The circumferential trough is created medially on the peripheral tibial plateau and on the anterior and posterior horn meniscal attachments using an arthroscopic shaver. The anterior and posterior horns of the meniscal allograft are secured to their attachments using transosseous suture fixation and arthroscopically placed inside-out sutures around the peripheral rim. (Adapted with permission from Boss A, Klimkiewicz J, Fu FH: Technical innovation: Creation of a peripheral vascularized trough to enhance healing in cryopreserved meniscal allograft reconstruction. Knee Surg Sports Traumatol Arthrosc 2000;8:159-162.) Jon K. Sekiya, MD, and Christopher I. Ellingson, MD Volume 14, Number 3, March 2006 169 bone bridge. The meniscal allograft is then fixed, as previously described. For medial meniscal allograft trans- plantation, placement and drilling of the posterior bone plug tunnel is fa- cilitated by passing the ACL graft af- ter the meniscal allograft is secured. In both the medial and lateral al- lograft procedures, tibial ACL al- lograft fixation is performed after me- niscal allograft placement and fixation. Postoperative Care There is no clear consensus concern- ing rehabilitation protocols for pa- tients who have undergone meniscal allograft transplantation; this is a re- sult, in part, of the lack of scientific studies on the topic. In general, weight-bearing and range-of-motion limitations typically are imposed in a fashion similar to that of a major meniscal repair, until meniscal al- lograft healing has occurred (usually by 8 to 12 weeks) (Figure 7). A con- comitant ACL reconstruction, when performed, also affects the rehabili- tation protocol, with motion empha- sized to prevent arthrofibrosis. 51 Full hyperextension symmetrical to the contralateral normal extremity typ- ically is the goal in the first few weeks. Full weight bearing and flex- ion beyond 90° usually is allowed af- ter 6 to 12 weeks postoperatively. V igorous, high-impact activities gen- erally are discouraged indefinitely. Fritz et al 52 protect meniscal transplants for the first 4 weeks us- ing a hinged range-of-motion brace at 0 to 90°. Kohn et al 51 use pro- longed epidural anesthesia to facili- tate postoperative continuous pas- sive motion until 0 to 90° is achieved. Fritz et al 52 allow patients to partially bear weight for the first week, with the brace locked in full extension to avoid shear, whereas Kohn et al 51 keep patients non– weight bearing for 3 weeks. Both groups advance weight bearing and discontinue crutches at 4 to 6 weeks for cases in which the patient has 90° to 100° of knee flexion, full knee extension, and minimal or absent swelling, and is able to walk without a bent-knee gait. At 6 weeks, closed chain exercises are started at 0 to 45°, progressing to 75°. Patients may return to sedentary work at 1 week, strenuous work at 3 to 4 months, low-impact exercises at 8 weeks, and running after 4 to 5 months. Al- though light or moderate sports are allowed at 6 to 9 months, strenuous sports are not recommended. Results Milachowski et al 53 performed the first isolated meniscal allograft transplant in 1984; the authors re- ported the results of 6 fresh-frozen (deep-frozen) and 16 freeze-dried al- lografts in 20 patients with a 14- month follow-up evaluation, includ- ing a second-look arthroscopy (Table 1, available at http:// jaaos.org/cgi/content/full/14/3/164/ DC1). Although fresh-frozen al- lografts were more likely to have an improved clinical appearance, both graft types showed a decrease in size, and neither showed signs of inflam- mation or rejection. Reaction at the synovial joint was more pronounced in the lyophilized group, as was graft shrinkage. The authors concluded that, overall, the fresh-frozen al- lografts showed better results, al- though the failure rates were compa- rable between the two groups. Garrett 40 presented results in 43 patients with a 2- to 7-year fol- low-up. Secondary procedures were performed in most of the patients, with 24 concomitant ACL recon- structions, 13 osteotomies, and 11 osteochondral allografts. Sixteen fresh and 27 cryopreserved grafts were used. Second-look arthroscopy was performed in 28 patients, with 20 grafts found to be intact. The main factor in failure was the degree of arthritis in the knees. Two fail- ures occurred in 32 patients with Outerbridge grade III chondromala- cia; 6 failures occurred in 11 patients with grade IV chondromalacia. Graft type did not appear to affect outcome. Figure 6 Anterior cruciate ligament insertion site (colored with ink) is in line with the medial meniscus anterior and posterior horns. A, Medial meniscus allograft flipped over laterally showing the medial extent of the anterior and posterior meniscus attachments. B, Medial meniscus allograft left in situ showing the lateral extent of the anterior and posterior meniscus attachments. Meniscal Allograft Transplantation 170 Journal of the American Academy of Orthopaedic Surgeons van Arkel and de Boer, 54 in 1995, reported the results of 23 cryopre- served allografts at 2- to 5-year follow-up. There were 20 clinical successes and 3 failures requiring graft removal. The authors consid- ered the failures to be secondary to uncorrected alignment. No immune response was noted in the failures. Cameron and Saha 55 performed allograft transplantation of 67 fresh- frozen irradiated grafts in 63 pa- tients. Osteotomies were performed in 34 patients; the average medial compartment varus was 7.1°, and average lateral compartment valgus, 5.9°. Mean follow-up was 31 months, and the success rate using the Lysholm knee rating scale was 87%. The authors emphasized that limb alignment is important in the outcome of meniscal transplanta- tions and recommended the need for further research to determine whether the meniscal allograft or re- alignment procedure was more im- portant in achieving pain relief. In eight patients who had had prior un- successful realignment procedures, insertion of the meniscal allograft resulted in one excellent, four very good, and three good results. A pro- spective study comparing realign- ment with and without meniscal al- lograft would help determine whether it was the realignment with or without the meniscal trans- plant, or both, that was responsible for improved outcomes. Carter 56 had favorable outcomes in 45 of 46 patients evaluated at an average of 2.9 years. Three grafts par- tially failed, and one graft complete- ly failed, requiring three partial meniscectomies and one total me- niscectomy. These failures were at- tributed to patient selection in two cases, technical error in one, and noncompliance in one. Internation- al Knee Documentation Committee (IKDC) scores revealed that all but the patient with complete graft fail- ure had improvement in pain. Second-look arthroscopy in 38 pa- tients showed healing at the menis- cal capsular repair site. MRI was not useful in evaluating graft integrity because no correlation was found be- tween abnormal signal intensity and second-look arthroscopies that re- vealed no abnormalities. Noyes and Barber-Westin 15 re- ported results of 96 meniscal al- lografts perfor med in 82 patients. Fresh-frozen grafts exposed to 2.5 mRad of gamma irradiation were used. Most grafts were fixed only at the posterior horn; no grafts were se- cured by both the anterior and poste- rior horns. Twenty-nine of the 96 grafts failed within 24 months, requir- ing removal; these were not included in the follow-up. Of the 67 meniscal transplants evaluated at 2 to 5 years, 27 failed. Overall results for all 96 al- lograft transplantations were 9% healed, 31% partially healed, 58% failed, and 2% lost to follow-up. A correlation between arthritic changes and meniscal healing was observed. Stollsteimer et al 57 reported results of 23 allografts in 22 patients followed for an average of 40 months. All al- lografts were nonirradiated and cryopreserved; surgery was arthro- scopically assisted with implantation using a bone plug technique. Postop- erative joint space narrowing mea- sured radiographically averaged 0.88 mm. Bilateral knee MRI was per- formed in 12 patients. All patients improved clinically, as measured at final follow-up with Tegner, L ysholm, and IKDC scores. In addition, allograft size was noted to have shrunk to an average of 63% of the normal con- tralateral side; the significance of the observed allograft shrinkage is not known. Figure 7 Arthroscopic images of healing of a medial meniscal allograft 4 months after transplantation. A, Suture fixation of medial meniscal allograft using arthroscopically placed, vertical mattress, inside-out sutures (arrow). B, Healed posterior horn that is stable with arthroscopic probing (arrow). C, Restoration of normal contour of the junction of the midbody and posterior horn (arrow). D, Healed midbody peripheral rim verified by direct arthroscopic visualization and probing (arrow). FC = femoral condyle, M = meniscus, TP = tibial plateau Jon K. Sekiya, MD, and Christopher I. Ellingson, MD Volume 14, Number 3, March 2006 171 All 18 patients evaluated by Rath et al 58 an average of 5.4 years after meniscal allograft transplantation had a marked decrease in pain and improvement in function. No joint space narrowing was observed on 45° posteroanterior weight-bearing radiographs; however, 8 of 22 al- lografts tore during the study period (5 as a result of trauma). After initial positive outcomes, these allograft failures required six partial and two total meniscectomies secondary to mechanical symptoms. Excised al- lografts were examined histological- ly and found to have reduced cellu- larity and cytokine expression compared with controls. Two pa- tients, both requiring total menis- cectomy after failure, requested re- implantation secondary to return of symptoms after the removal of al- lograft menisci; these two patients were included in the study from time of reimplantation. It is postu- lated that allograft menisci have a reduced functionality secondary to repopulation with fewer cells, as measured by this decrease in growth factor production. Verdonk 59 found a notable differ- ence in preoperative and postopera- tive pain scores, with 87% of postop- erative patients stating that they would undergo transplantation again. There were no significant dif- ferences between isolated medial or lateral meniscus transplants. Wirthetal 60 reported the long- term results of 23 meniscal trans- plantations with simultaneous ACL reconstructions, measured an average of 3 and 14 years postoperatively. Seventeen lyophilized and six deep- frozen grafts were used. Although MRI and arthroscopy demonstrated a reduction in the size of lyophilized grafts, all patients improved in Lysholm scores. Deep-frozen menis- cal allograft patients did better in both objective and subjective results compared with lyophilized allograft patients. van Arkel and de Boer 61 recently evaluated 63 meniscal allografts in 57 patients at an average follow-up of 60 months. Thirty-four patients had isolated lateral meniscal transplanta- tion, 17 had isolated medial meniscal transplantation, and 6 had combined transplantation. Preoperative insta- bility secondary to ACL deficiency or meniscectomy was present in 21 pa- tients; postoperative stability was achieved in 11 of these patients. Al- lograft failure, measured by persis- tent pain or mechanical failure, oc- curred in 13 transplantations (5 lateral, 7 medial, and 1 medial and lateral). The cumulative survival rate of lateral, medial, and combined al- lografts was 76%, 50%, and 67%, re- spectively. Rupture of the ACL had a significant (P = 0.003) negative corre- lation with successful medial menis- cal transplantation. Additionally, lat- eral meniscal transplantations did significantly (P = 0.004) better than medial transplantations clinically. Biomechanical function and ana- tomic differences likely explain this difference. Medial meniscal allograft survival should improve with con- current ACL reconstruction in the ACL-deficient knee. Yoldas et al 42 evaluated 31 patients with meniscal transplants, twenty of which were combined with ACL re- constructions, with a minimum 2-year follow-up. Thirty of the 31 pa- tients had a normal or nearly normal rating according to IKDC knee func- tion and activity level. Nineteen of the knees that underwent combined meniscal transplant and ACL recon- struction were normal or nearly nor- mal according to IKDC stability test- ing. The average single-leg hop and vertical jump was 85% that of the contralateral limb. No progressive joint space narrowing was seen on ra- diographic examination. Sekiya et al 62 evaluated 25 pa- tients who underwent isolated later- al meniscal transplantation at an av- erage follow-up of 3.3 years. Bony fixation of the allograft was per- formed in 17 patients; 8 patients had suture fixation of the anterior and posterior horns of the meniscal al- lograft. In these patients, 79% had normal or nearly normal scores ac- cording to IKDC knee function, ac- tivity level, and overall subjective ratings. Medical Outcomes Study 36-Item Short Form (SF-36) physical and mental component summary scores revealed that transplant recip- ients performed at higher levels than age- and sex-matched population controls. The average scores for the single-leg hop and vertical jump test were 91% and 85%, respectively, of the contralateral limb. There was no joint space narrowing seen over time on radiographic examination. In ad- dition, radiographic preoperative and postoperative joint space measure- ments of the involved lateral com- partment were significantly (P ≤ 0.05) associated with mean lower subjective assessment, symptoms, sports activity score, Lysholm score, and final IKDC rating at latest follow-up. Finally, patients treated with the bony technique had signif- icantly (P ≤ 0.05) better range of mo- tion, according to IKDC criteria, at latest follow-up compared with the suture fixation group. Sekiya et al 31 also evaluated 28 patients who underwent combined meniscal transplantation with ACL reconstruction (average follow-up, 2.8 years). Of these patients, 86% to 90% had normal or nearly normal scores, according to IKDC overall subjective and symptoms assess- ment. Combined ACL and meniscal transplantation patients scored at higher levels on SF-36 physical and mental component summary scores than did age- and sex-matched popu- lations. Ninety percent of the pa- tients also had normal or nearly nor- mal scores by Lachman’s scoring system and pivot-shift testing. KT- 1000 testing at both 20 lb and at maximum manual demonstrated an average of 1.5 mm of increased ante- rior translation compared with the normal contralateral knee. No joint space narrowing was seen over time on radiographic examination. 31 Meniscal Allograft Transplantation 17 2 Journal of the American Academy of Orthopaedic Surgeons Recently, Graf et al 30 retrospec- tively reviewed nine patients who had undergone combined medial me- niscal transplantation and ACL re- construction (minimum follow-up, 8.5 years; average follow-up, 9.7 years). One allograft was removed be- cause of the presence of a presumed low-grade infection. Seven of eight patients had normal or nearly normal IKDC scores while remaining at their preoperative radiographic score lev- els without progression. Six of eight patients were extremely pleased with their knee function and were highly active in recreational sports. Six of eight patients also had normal or nearly normal scores, according to IKDC functional testing. Finally, all eight patients stated that they would recommend the procedure to a friend and would undergo the procedure again, given similar circumstances. 30 Summary Meniscal transplantation continues to evolve as a treatment for difficult meniscal injuries that necessitate partial or total meniscectomy. Initial clinical results are promising, but long-term clinical outcomes remain to be established. Important surgical factors include patient selection, limb stability and alignment, graft sizing, graft placement, and graft fix- ation. Currently, meniscal allograft transplantation should be considered a salvage operation for symptomatic meniscal deficiency in the young pa- tient. Nonetheless, with careful pa- tient selection, this procedure can predictably relieve compartmental pain and restore knee stability (for medial meniscal transplantation) when associated with combined ACL reconstruction. In addition, meniscal allograft transplantation may par- tially restore native meniscal func- tion, as is seen with slowing of the degenerative ar thritic process in transplanted meniscus-deficient knee compartments. References Evidence-based Medicine: Studies referenced are primarily case-control reports of meniscal allografts (level III). There are no prospective, ran- domized studies on this topic to date (level I, II studies). Citation numbers printed in bold type indicate references published within the past 5 years. 1. Beaupre A, Choukroun R, Guidouin R, Garneau R, Gerardin H, Cardou A: Knee menisci: Correlation between microstructure and biomechanics. Clin Orthop Relat Res 1986;208:72- 75. 2. McDevitt CA, Webber RJ: The ultra- structure and biochemistry of menis- cal cartilage. Clin Orthop Relat Res 1990;252:8-18. 3. Greis PE, Bardana DD, Holmstrom MC, Burks RT: Meniscal injury: I. Ba- sic science and evaluation. JAm Acad Orthop Surg 2002;10:168-176. 4. Arnoczky SP, Warren RF: Microvas- culature of the human meniscus. Am J Sports Med 1982;10:90-95. 5. Dye SF, Vaupel GL, Dye CC: Con- scious neurosensor y mapping of the internal structures of thehuman knee without intraarticular anesthesia. Am J Sports Med 1998;26:773-777. 6. Vandermeer RD, Cunningham FK: Arthroscopic treatment of the discoid lateral meniscus: Results of long- term follow-up. Arthroscopy 1989;5: 101-109. 7. Johnson DL, Swenson TM, Livesay GA, Aizawa H, Fu FH, Harner CD: Insertion-site anatomy of the human menisci: Gross, arthroscopic, and to- pographical anatomyas abasis forme- niscal transplantation. Arthroscopy 1995;11:386-394. 8. Thompson WO, Thaete FL, Fu FH, Dye SF: Tibial meniscal dynamics us- ing three-dimensional reconstruction of magnetic resonance images. Am J Sports Med 1991;19:210-216. 9. Voloshin AS, Wosk J: Shock absorp- tion of meniscectomized and painful knees: A comparative in-vivo study. J Biomed Eng 1983;5:157-161. 10. Levy IM, Torzilli PA, Warren RF: The effect of medial meniscectomy on an- terior posterior motion of the knee. J Bone Joint Surg Am 1982;64:883- 887. 11. Verdonk R, Kohn D: Harvest and con- servation of meniscal allografts. Scand J Med Sci Sports 1999;9:158- 159. 12. Jackson DW, Whelan J, Simon TM: Cell survival after transplantation of fresh meniscal allografts: DNA probe analysis in a goat model. Am J Sports Med 1993;21:540-549. 13. Jackson DW, Windler GE, Simon TM: Intra-articular reaction associated with use of freeze-dried, ethylene oxide-sterilized bone-patella tendon- bone allografts in the reconstruction of the anterior cruciate ligament. Am J Sports Med 1990;18:1-11. 14. Yahia L, Zukor D: Irradiated meniscal allotransplants of rabbits: Study ofthe mechanical properties at six months postoperation. Acta Orthop Belg 1994;60:210-215. 15. Noyes FR, Barber-Westin SD: Irradiat- ed meniscus allografts in the human knee: A two to five year follow-up. Orthop Trans 1989;19:417. 16. Goble EM, Kohn D, Verdonk R, Kane M: Meniscal substitutes – human ex- perience. Scand J Med Sci Sports 1999;9:146-157. 17. Rodeo SA, Senevirante A, Suzuki K, Felker K, Wickiewicz TL, Warren RF: Histological analysis of human me- niscal allografts. J Bone Joint Surg Am 2000;82:1071-1082. 18. Arnoczky SP, McDevitt CA, Schmidt MB, Mow VC, Warren RF: The effect of cryopreservation in canine menis- ci: A biomechanical morphologic and biomechanical evaluation. J Orthop Res 1988;6:1-12. 19. Jackson DW, McDevitt CA, Simon TM, Arnoczky SP, Atwell EA, Silvino NJ: Meniscal transplantation using fresh and cryopreserved allografts: An experimental study in goats. Am J Sports Med 1992;20:644-656. 20. Yamazaki K, Tachibana Y: Vascular- ized synovial flap promoting regener- ation of the cryopreserved meniscal allograft: Experimental study in rab- bits. J Orthop Sci 2003;8:62-68. 21. Fabbriciani C, Lucania L, Milano G, Schiavone Panni A, Evangelisti M: Meniscal allografts:Cryopreservation vs. deep-frozen techniques. An exper- imental study in goats. Knee Surg Sports Traumatol Arthrosc 1997;5: 124-134. 22. Debeer P, Decorte R,Delvaux S, Belle- mans J: DNA analysis of a transplant- ed cryopreserved meniscal allograft. Arthroscopy 2000;16:71-75. 23. Paletta GA Jr, Manning T, Snell E, Parker R, Bergfeld J: The effect of al- lograft meniscal replacement on in- traarticular contactarea and pressures in the human knee: A biomechanical study. Am J Sports Med 1997;25:692- 698. Jon K. Sekiya, MD, and Christopher I. Ellingson, MD Volume 14, Number 3, March 2006 17 3

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