Meniscus Allograft Transplantation in Conjunction with Arthroscopic Biologic Knee Restoration Delays Arthroplasty in Patients Over 50 Years of Age.

PURPOSE: The purpose of this study is to evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years of age previously advised joint arthroplasty. METHODS: One hundred eight meniscus allograft transplants (MATs) using the arthroscopic three tunnel technique between 1997 and 2019 in patients over 50 years of age were retrospectively reviewed with two-year minimum follow-up period. Inclusion criteria were patients recommended knee arthroplasty with pain and preservation of some joint space by standing flexion x-rays. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol or complete research questionnaires. International Knee Documentation Committee (IKDC) composite and isolated pain scale were evaluated longitudinally. Time from MAT to arthroplasty was measured with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain. RESULTS: Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range of 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (p<0.001) in pain and function as assessed by IKDC. These improvements were sustained ten years post-operatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference (MCID) through 10 years post-operatively. CONCLUSIONS: Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates over 50 years of age. Influences of concomitant procedures cannot be defined.

Articular cartilage paste graft for severe osteochondral lesions of the knee: a 10- to 23-year follow-up study.

PURPOSE: The purpose of this study is to evaluate the clinical outcomes of the articular cartilage paste graft procedure at a minimum of 10 years from surgery. It is hypothesized that articular cartilage paste grafting can provide patients with a durable repair of severe full-thickness osteochondral injuries, measured by persistence of procedure-induced benefit and subjective outcome scores at 10 or more years. METHODS: Seventy-four patients undergoing paste grafting at a mean age of 45.3 ± 10.8 years (range 13-69 years) were followed up at a mean of 16.8 ± 2.4 years (range 10.6-23.2 years) post-operatively using validated subjective outcome measures; Kaplan-Meier survival analysis was performed to estimate expected population benefit time. RESULTS: Kaplan-Meier estimated median benefit time of 19.1 years (mean: 16.6 ± 0.9 years) for all patients undergoing paste grafting. Thirty-one (41.9 %) patients had progressed to arthroplasty at a mean of 9.8 ± 5.6 years (range 0.4-20.6 years). Ninety percent of patients reported that the procedure provided good to excellent pain relief. Median IKDC subjective score increased significantly at most recent follow-up (70.1) compared to preoperative (55.7, p = 0.013). Median WOMAC scores decreased significantly from 26 to 14 (p = 0.001). Median Tegner score increase from 4 to 6 was not found to be significant (ns). VAS pain averaged 23/100 at most recent follow-up. CONCLUSIONS: Patients who underwent the paste grafting reported improved pain, function, and activity levels for an expected mean of 16.6 years, and for those who ultimately progressed to knee replacement, surgical treatment including the paste graft was able to delay arthroplasty until a mean age of 60.2 years, an age at which the procedure is commonly performed. Full-thickness articular cartilage loss can be successfully treated, reducing pain, and improving function, using this single-step, inexpensive arthroscopic procedure. LEVEL OF EVIDENCE: IV.

Meniscus transplantation in an active population with moderate to severe cartilage damage.

PURPOSE: The purpose of this study was to evaluate the efficacy of meniscus allograft transplantation in an active patient population with moderate to severe cartilage damage and the procedure's ability to allow sports participation postoperatively. METHODS: Forty-nine patients with moderate to severe cartilage damage who underwent meniscus allograft transplantation were included in this study; those with symptoms related to articular cartilage damage also underwent articular cartilage repair. Kaplan-Meier (KM) survival estimate, potential hazards to survival, and subjective clinical outcomes were analyzed. For KM survival, failure was defined as progression to knee arthroplasty, surgical removal of the meniscus transplant without revision, a self-reported follow-up pain level that was more than preoperative level, or constant moderate pain with no relief from non-operative treatment. RESULTS: The mean follow-up time was 8.6 ± 4.2 years. The mean age at surgery was 45.3 ± 12.9 years. Meniscus transplantation was performed in 37 medial cases and 12 lateral cases. There were 41 patients with Outerbridge Grade IV and 8 with Grade III. Thirty-six (73.5%) patients were able to participate in sporting activities postoperatively. Eleven (22.4%) meniscus transplants failed at an average of 5.2 ± 4.4 years. The KM mean estimated survival time was 12.6 ± 0.7 years. No tested risks were found to affect sports participation or procedure success. CONCLUSIONS: Meniscus transplantation is a viable surgical option for patients with severe cartilage damage and missing or irreparable menisci to provide significant improvements in pain and function levels in the medium to long term with the majority of patients achieving their goal of participation in sporting activities. These results indicate that symptomatic patients may be able to participate in sports activities for an average of 12.6 years following meniscus transplantation. LEVEL OF EVIDENCE: Case series, Level IV.

Xenograft bone-patellar tendon-bone ACL reconstruction: a case series at 20-year follow-up as proof of principle.

PURPOSE: ACL reconstruction has a significant failure rate. To address the need for inexpensive strong tissue, a treatment process to "humanize" porcine tissue was developed and tested in primates and humans. This report describes the long-term outcomes from the first human clinical trial using a porcine xenograft ACL reconstruction device. METHODS: The study was performed with Z-Lig™ xenograft ACL device in 2003 as a pilot clinical feasibility study. This device was processed to slow its immune-mediated destruction by enzymatic elimination of α-gal epitopes and by partial crosslinking to slow the infiltration of macrophages into the biotransplant. RESULTS: Ten patients underwent reconstruction with the Z-Lig™ device. Five of 10 patients failed due to subsequent trauma (n = 3), arthrofibrosis (n = 1), and surgical technical error (n = 1). One patient was lost to follow-up after the 12-year evaluation. Each remaining patient reported a stable fully athletic knee. Physical exams are consistent with a score of less than one on the ACL stability tests. MRIs demonstrate mature remodeling of the device. There is no significant degradation in patient-reported outcome scores, physical exams, or MRI appearance from 12 to 20-year follow-ups. CONCLUSIONS: The studies in a small group of patients have demonstrated that implantation of porcine ligament bioprosthesis into patients with torn ACLs can result in the reconstruction of the bioprosthesis into autologous ACL that remains successful over 20 years. The possibility of humanizing porcine tissue opens the door to unlimited clinical material for tissue reconstructions if supported by additional clinical trials. LEVEL OF EVIDENCE: IV, case series.

Osteochondral Autograft Plugs versus Paste Graft: Ex Vivo Morselization Increases Chondral Matrix Production.

OBJECTIVE: Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs. DESIGN: This institutional review board-approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology. RESULTS: Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively (P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant (P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae. CONCLUSIONS: Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.

Replacement of human anterior cruciate ligaments with pig ligaments: a model for anti-non-gal antibody response in long-term xenotransplantation.

BACKGROUND: Understanding anti-non-gal antibody response is of significance for success in xenotransplantation. Long-term anti-non-gal response in humans was studied in patients transplanted with porcine patellar tendon (PT) lacking alpha-gal epitopes, for replacing ruptured anterior cruciate ligament (ACL). METHODS: Porcine PTs were treated with recombinant alpha-galactosidase to eliminate alpha-gal epitopes and with glutaraldehyde for moderate cross-linking of collagen fibers. The processed pig PTs were implanted to replace ruptured ACL in patients. RESULTS: In five of six evaluable subjects, the xenografts have continued to function for over two years and passed all functional stability assessments. Thus, processed porcine PT seems to be appropriate for replacing ruptured human ACL. Enzyme-linked immunosorbent assay and Western blot studies indicated that all subjects produced anti-non-gal antibodies against multiple pig xenoproteins, but not against human ligament proteins. Production of anti-non-gal antibodies peaked two to six months posttransplantation and disappeared after two years. CONCLUSIONS: These antibodies contribute to a low-level inflammatory process that aids in gradual xenograft replacement by infiltrating host fibroblasts that align with the pig collagen "scaffold" and secrete collagen matrix. The assays monitoring anti-non-gal antibodies will help to determine whether long-term survival of live organ xenografts requires complete suppression of this antibody response.

Meniscal sizing based on gender, height, and weight.

PURPOSE: Successful meniscus transplantation may depend on accurate sizing. Meniscal sizing is currently determined by measuring a combination of bony landmarks and soft-tissue insertion points through images obtained radiographically or by magnetic resonance imaging (MRI). The literature widely reports inaccuracy in sizing resulting from radiographic errors in magnification, erroneous identification of bony landmarks, and difficulty in differentiating between the soft-tissue and bone interface. In our meniscus transplantations we have observed that when the height and weight of the recipient matched those of the donor, the meniscal size appeared to be a match at surgical implantation; we designed this study to confirm this observation. METHODS: The MRI-based meniscal sizing of 111 patients (63 male and 38 female patients; mean age, 44 years [range, 15 to 76 years]), totaling 147 menisci (87 lateral and 60 medial), was compared with the height, weight, gender, and body mass index (BMI) of each patient. MRI scans were obtained with a 1.0-Tesla MRI system (ONI Medical Systems, Wilmington, MA). Sizing was performed by an independent musculoskeletal MRI radiologist as established by the literature. Statistical methods include nonparametric Pearson correlation (r) between MRI-based lateral meniscal width, lateral meniscal length, medial meniscal width, medial meniscal length, total tibial plateau width, and patient height, weight, gender, and BMI. Significance at the P = .05 level was used. RESULTS: Height was found to have a linear relationship to total tibial plateau, which has a good predictive correlation with meniscal dimensions of r > 0.7. Female patients generally present with smaller dimensions than male patients. High-BMI groups present with significantly larger meniscal dimensions than low-BMI groups at any given height. CONCLUSIONS: Height, weight, and gender are easily obtained variables and are proportional to meniscal tissue dimensions. These exploratory statistics establish correlations between height, weight, gender, total tibial plateau width, and meniscal size. CLINICAL RELEVANCE: Height, weight, and gender should be considered by both tissue banks and surgeons as fast and cost-effective variables by which to predict meniscal dimensions.

Anterior cruciate ligament reconstruction with a porcine xenograft: a serologic, histologic, and biomechanical study in primates.

PURPOSE: This study proposes treatment methods to provide a mechanically competent, immunocompatible, and sterile porcine graft for human knee ligament reconstruction. METHODS: The anterior cruciate ligament (ACL) was reconstructed by using treated porcine patellar tendon grafts or controls of untreated porcine grafts or allografts in 20 rhesus monkeys. Animals were stratified into 2-, 6-, and 12-month postreconstruction cohorts. Serologic and histologic assessments were performed to evaluate host immunological and cellular response. Healing and functional integrity of the ACL reconstructions were assessed by tensile biomechanical testing. RESULTS: Untreated porcine grafts were acutely resorbed and rejected, whereas treated porcine grafts and allografts were incorporated by the host as functional grafts. Temporal histologic assessment of treated porcine grafts and rhesus grafts revealed gradual host cellular infiltration and graft collagen remodeling through a similar mechanism of ligamentization. Biomechanical evaluations support graft functional integration with no difference between allograft and treated graft reconstructions. CONCLUSION: Rhesus allograft and treated porcine grafts presented with similar healing profiles in a long-term evaluation of ACL reconstruction. CLINICAL RELEVANCE: Immunochemical modification and sterilization of porcine patellar tendon grafts may improve initial biocompatibility and long-term functionality of xenografts in musculoskeletal applications.

Meniscus allograft survival in patients with moderate to severe unicompartmental arthritis: a 2- to 7-year follow-up.

PURPOSE: We present meniscus allograft survival data at least 2 years from surgery for 45 patients (47 allografts) with significant arthrosis to determine if the meniscus can survive in an arthritic joint. TYPE OF STUDY: Prospective, longitudinal survival study. METHODS: Data were collected for 31 men and 14 women, mean age 48 years (range, 14 to 69 years), with preoperative evidence of significant arthrosis and an Outerbridge classification greater than II. Failure is established by previous studies as allograft removal. No patient was lost to follow-up. RESULTS: The success rate was 42 of 47 allografts (89.4%) with a mean failure time of 4.4 years as assessed by Kaplan-Meier survival analysis. Statistical power is greater than 0.9, with alpha = 0.05 and N = 47. There was significant mean improvement in preoperative versus postoperative self-reported measures of pain, activity, and functioning, with P = .001, P = .004, and P = .001, respectively, as assessed by a Wilcoxon rank-sum test with P = .05. CONCLUSIONS: Meniscus allografts can survive in a joint with arthrosis, challenging the contraindications of age and arthrosis severity. These results compare favorably with those in previous reports of meniscus allograft survival in patients without arthrosis. LEVEL OF EVIDENCE: Level IV.

Articular cartilage paste grafting to full-thickness articular cartilage knee joint lesions: a 2- to 12-year follow-up.

PURPOSE: To prospectively assess clinical outcomes and regeneration of osteoarthritic cartilage lesions treated with an articular cartilage paste grafting technique. TYPE OF STUDY: Prospective, longitudinal case series. METHODS: We treated 125 patients (136 procedures; 34% female, 66% male; mean age, 46 years; range, 17 to 73 years) with an Outerbridge classification of grade IV lesions with an articular cartilage paste graft. Clinical data were recorded 2 to 12 years from surgery, with 20 of 145 patients lost to follow-up over 12 years (13.7%). Clinical outcomes were captured annually with validated Western Ontario and McMaster Universities Arthritis Index (WOMAC), International Knee Documentation Committee (IKDC), and Tegner subjective questionnaires. Regenerated cartilage biopsy specimens were obtained at second-look arthroscopy from 66 patients and evaluated as to quality and quantity of defect fill by a blinded, independent histopathology reviewer. RESULTS: Preoperative versus postoperative validated pain, functioning, and activity measures improved significantly (P< .001). Clinically, 18 of the 125 patients were considered failures (14.4%), with 10 patients undergoing subsequent joint arthroplasty and 8 who reported worse pain after surgery. Regional histologic variation occurred. Forty-two of 66 biopsy specimens (63.6%) showed strong and consistent evidence of replacement of their articular surface, and 18 of 66 biopsy specimens (27.3%) showed development of areas of cartilage. CONCLUSIONS: Paste grafting is a low-cost, 1-stage arthroscopic treatment for patients with Outerbridge classification grade IV arthritic chondral lesions. The procedure offers excellent, long-lasting, pain relief, restored functioning, and possibility of tissue regeneration for patients with painful chondral lesions in both arthritic and traumatically injured knees. LEVEL OF EVIDENCE: Level IV, case series.

Meniscal allografting: the three-tunnel technique.

This technical note describes an improved arthroscopic technique of meniscal transplantation that simplifies the surgical procedure and secures the allograft to the tibia at 3 sites. The technique is useful for both medial and lateral meniscal transplantation and has been used in our clinic for over 60 meniscal transplantation procedures.

Osteochondral grafting for failed knee osteochondritis dissecans repairs.

BACKGROUND: Revision of failed surgical treatments of osteochondritis dissecans (OCD) lesions remains a challenge without an obvious solution. The aim of this study was to evaluate seven consecutive patients undergoing osteochondral grafting of a failed OCD repair. METHODS: The mean time from surgery to the latest evaluation was 7.0 years. IKDC, WOMAC, Tegner, and MRI studies were collected both preoperatively and during follow-up. Evaluation of the graft was assessed using the magnetic resonance observation of cartilage repair tissue (MOCART) grading system. RESULTS: Over the course of the study period, five patients required additional surgery with a study median of one additional surgery (range, zero to 3). At most recent follow-up, there was significant improvement from preoperative values in median IKDC (p=0.004), WOMAC (p=0.030), and Tegner (p=0.012). Complete cartilage fill and adjacent tissue integration of the paste graft were observed by MRI evaluation in five of the seven (71.4%) patients. Definitive correlation between clinical outcomes and MRI scores was not observed. CONCLUSIONS: This study shows promising results of osteochondral grafting as a viable option for the revision of failed OCD lesion repairs; however, more patients are needed to fully support its efficacy in these challenging failed revision cases.