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Changes in Cross-sectional Area and Signal Intensity of Healing Anterior Cruciate Ligaments and Grafts in the First 2 Years After Surgery.

ABSTRACT: BACKGROUND:The quality of a repaired anterior cruciate ligament (ACL) or reconstructed graft is typically quantified in clinical studies by evaluating knee, lower extremity, or patient performance. However, magnetic resonance imaging of the healing ACL or graft may provide a more direct measure of tissue quality (ie, signal intensity) and quantity (ie, cross-sectional area). HYPOTHESES:(1) Average cross-sectional area or signal intensity of a healing ACL after bridge-enhanced ACL repair (BEAR) or a hamstring autograft (ACL reconstruction) will change postoperatively from 3 to 24 months. (2) The average cross-sectional area and signal intensity of the healing ligament or graft will correlate with anatomic features of the knee associated with ACL injury. STUDY DESIGN:Cohort study; Level of evidence, 2. METHODS:Patients with a complete midsubstance ACL tear who were treated with either BEAR (n = 10) or ACL reconstruction (n = 10) underwent magnetic resonance imaging at 3, 6, 12, and 24 months after surgery. Images were analyzed to determine the average cross-sectional area and signal intensity of the ACL or graft at each time point. ACL orientation, stump length, and bony anatomy were also assessed. RESULTS:Mean cross-sectional area of the grafts was 48% to 98% larger than the contralateral intact ACLs at all time points (P < .01). The BEAR ACLs were 23% to 28% greater in cross-sectional area than the contralateral intact ACLs at 3 and 6 months (P < .02) but similar at 12 and 24 months. The BEAR ACLs were similar in sagittal orientation to the contralateral ACLs, while the grafts were 6.5° more vertical (P = .005). For the BEAR ACLs, a bigger notch correlated with a bigger cross-sectional area, while a shorter ACL femoral stump, steeper lateral tibial slope, and shallower medial tibial depth were associated with higher signal intensity (R2 > .40, P < .05). Performance of notchplasty resulted in an increased ACL cross-sectional area after the BEAR procedure (P = .007). No anatomic features were correlated with ACL graft size or signal intensity. CONCLUSION:Hamstring autografts were larger in cross-sectional area and more vertically oriented than the native ACLs at 24 months after surgery. BEAR ACLs had a cross-sectional area, signal intensity, and sagittal orientation similar to the contralateral ACLs at 24 months. The early signal intensity and cross-sectional area of the repaired ACL may be affected by specific anatomic features, including lateral tibial slope and notch width-observations that deserve further study in a larger cohort of patients. REGISTRATION:NCT02292004 (ClinicalTrials.gov identifier).

SUBMITTER: Kiapour AM

PROVIDER: S-EPMC6599545 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Changes in Cross-sectional Area and Signal Intensity of Healing Anterior Cruciate Ligaments and Grafts in the First 2 Years After Surgery.

Kiapour Ata M AM Ecklund Kirsten K Murray Martha M MM Flutie Brett B Freiberger Christina C Henderson Rachael R Kramer Dennis D Micheli Lyle L Thurber Laura L Yen Yi-Meng YM Fleming Braden C BC

The American journal of sports medicine 20190605 8

<h4>Background</h4>The quality of a repaired anterior cruciate ligament (ACL) or reconstructed graft is typically quantified in clinical studies by evaluating knee, lower extremity, or patient performance. However, magnetic resonance imaging of the healing ACL or graft may provide a more direct measure of tissue quality (ie, signal intensity) and quantity (ie, cross-sectional area).<h4>Hypotheses</h4>(1) Average cross-sectional area or signal intensity of a healing ACL after bridge-enhanced ACL ...[more]

PMID: 31166701

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Project description:BackgroundPrimary repair of the anterior cruciate ligament (ACL) augmented with a tissue engineered scaffold to facilitate ligament healing is a technique under development for patients with ACL injuries. The size (the amount of tissue) and signal intensity (the quality of tissue) of the healing ligament as visualized on magnetic resonance imaging (MRI) have been shown to be related to its strength in large animal models.HypothesisBoth modifiable and nonmodifiable risk factors could influence the size and signal intensity of the repaired ligament in patients at 6 months after surgery.Study designCase series; Level of evidence, 4.Methods62 patients (mean age, 19.4 years; range, 14-35 years) underwent MRI of the knee 6 months after ACL repair augmented with an extracellular matrix scaffold. The signal intensity (normalized to cortical bone) and average cross-sectional area of the healing ligament were measured from the MRI stack obtained by use of a gradient echo sequence. Associations between these 2 measures and patient characteristics, which included demographic, clinical, and anatomic features, were determined by use of multivariable regression analysis.ResultsA larger cross-sectional area of the repaired ligament at 6 months was associated with male sex, older age, and the performance of a larger notchplasty ( P < .05 for all associations). A lower signal intensity at 6 months, indicating greater similarity to normal ligament, was associated with a smaller tibial slope and greater side-to-side difference in quadriceps strength 3 months after surgery. Other factors, including preoperative body mass index, mechanism of injury, tibial stump length, and Marx activity score, were not significantly associated with either MRI parameter at 6 months.ConclusionModifiable factors, including surgical notchplasty and slower recovery of quadriceps strength at 3 months, were associated with a larger cross-sectional area and improved signal intensity of the healing ACL after bridge-enhanced ACL repair in this preliminary study. Further studies to determine the optimal size of the notchplasty and the most effective postoperative rehabilitation strategy after ACL repair augmented by a scaffold are justified.RegistrationNCT02664545 (ClinicalTrials.gov identifier).

Project description:Although anterior cruciate ligament (ACL) reconstruction is the treatment gold standard for ACL injury, it does not reduce the risk of posttraumatic osteoarthritis. Therefore, new treatments that minimize this postoperative complication are of interest. Bioenhanced ACL repair, in which a bioactive scaffold is used to stimulate healing of an ACL transection, has shown considerable promise in short-term studies. The long-term results of this technique and the effects of the bioenhancement on the articular cartilage have not been previously evaluated in a large animal model.(1) The structural (tensile) properties of the porcine ACL at 6 and 12 months after injury are similar when treated with bioenhanced ACL repair, bioenhanced ACL reconstruction, or conventional ACL reconstruction, and all treatments yield results superior to untreated ACL transection. (2) After 1 year, macroscopic cartilage damage following bioenhanced ACL repair is similar to that in bioenhanced ACL reconstruction and less than in conventional ACL reconstruction and untreated ACL transection.Controlled laboratory study.A total of 64 Yucatan mini-pigs underwent ACL transection and randomization to 4 experimental groups: no treatment, conventional ACL reconstruction, bioenhanced ACL reconstruction using a bioactive scaffold, and bioenhanced ACL repair using a bioactive scaffold. The biomechanical properties of the ligament or graft were examined and macroscopic assessments of the cartilage surfaces were performed after 6 and 12 months of healing.The structural properties (ie, linear stiffness, yield, and maximum loads) of the ligament after bioenhanced ACL repair were not significantly different from those in bioenhanced ACL reconstruction or conventional ACL reconstruction but were significantly greater than those in untreated ACL transection after 12 months of healing. Macroscopic cartilage damage after bioenhanced ACL repair was significantly less than that in untreated ACL transection and bioenhanced ACL reconstruction, and there was a strong trend (P = .068) for less macroscopic cartilage damage than in conventional ACL reconstruction in the porcine model at 12 months.Bioenhanced ACL repair produces a ligament that is biomechanically similar to an ACL graft and provides chondroprotection to the joint after ACL surgery.Bioenhanced ACL repair may provide a new, less invasive treatment option that reduces cartilage damage following joint injury.

Project description:BackgroundThe use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft.PurposeTo establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR.Study designControlled laboratory study.MethodsSurplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression.ResultsVancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05).ConclusionVancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment.Clinical relevanceVancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity.

Project description:This review describes a novel method developed for processing porcine tendon and other ligament implants that enables in situ remodeling into autologous ligaments in humans. The method differs from methods using extracellular matrices (ECMs) that provide postoperative orthobiological support (i.e., augmentation grafts) for healing of injured ligaments, in that the porcine bone-patellar-tendon-bone itself serves as the graft replacing ruptured anterior cruciate ligament (ACL). The method allows for gradual remodeling of porcine tendon into autologous human ACL while maintaining the biomechanical integrity. The method was first evaluated in a preclinical model of monkeys and subsequently in patients. The method overcomes detrimental effects of the natural anti-Gal antibody and harnesses anti-non-gal antibodies for the remodeling process in two steps: Step 1. Elimination of ?-gal epitopes-this epitope that is abundant in pigs (as in other nonprimate mammals) binds the natural anti-Gal antibody, which is the most abundant natural antibody in humans. This interaction, which can induce fast resorption of the porcine implant, is avoided by enzymatic elimination of ?-gal epitopes from the implant with recombinant ?-galactosidase. Step 2. Partial cross-linking of porcine tendon with glutaraldehyde-this cross-linking generates covalent bonds in the ECM, which slow infiltration of macrophages into the implant. Anti-non-gal antibodies are produced in recipients against the multiple porcine antigenic proteins and proteoglycans because of sequence differences between human and porcine homologous proteins. Anti-non-gal antibodies bind to the implant ECM, recruit macrophages, and induce the implant destruction by directing proteolytic activity of macrophages. Partial cross-linking of the tendon ECM decreases the extent of macrophage infiltration and degradation of the implant and enables concomitant infiltration of fibroblasts that follow the infiltrating macrophages. These fibroblasts align with the implant collagen fibers and secrete their own collagen and other ECM proteins, which gradually remodel the porcine tendon into human ACL. This ligamentization process lasts ?2 years and the biomechanical integrity of the graft is maintained throughout the whole period. These studies are the first, and so far the only, to demonstrate remodeling of porcine tendon implants into permanently functional autologous ACL in humans.

Dataset Information

Changes in Cross-sectional Area and Signal Intensity of Healing Anterior Cruciate Ligaments and Grafts in the First 2 Years After Surgery.

Publications

Changes in Cross-sectional Area and Signal Intensity of Healing Anterior Cruciate Ligaments and Grafts in the First 2 Years After Surgery.

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