Willemijn H. van Deursen
MD Student with Scholarly Concentration in Molecular Basis of Medicine, expected graduation Spring 2026
All Publications
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Immune Rejection of Orthopedic Tissue Allograft Scoping Review: Are we missing a cause of graft/procedural failure?: current concepts.
Journal of ISAKOS : joint disorders & orthopaedic sports medicine
2025: 101002
Abstract
Allograft transplants are commonly used in orthopedics. Unlike other transplanted tissues, orthopaedic tissue allografts are not HLA-matched. The clinical impact of immune response to allografts is poorly understood. Recent experience with allograft failures and reactions to ACL, MPFL, osteochondral, and meniscus transplants raises concern. This scoping review examines the literature on immunologic rejection of orthopedic tissue allograft using PubMed, Embase, Web of Science, and Scopus for studies describing immune rejection of orthopedic tissue allografts in humans and animals. Four reviewers independently screened titles/abstracts based on these criteria. Full texts were screened independently by two reviewers for inclusion. Variables of interest included the species, graft type, and graft treatment. Our literature search yielded 1625 articles, with 78 meeting the inclusion criteria. Of these studies, 30 (38.5%) were in humans, 16 (20.5%) in rats, and 11 (14.1%) in dogs. The remaining 21 studies were in a combination of rabbit, primate, mice, sheep, and cat subjects. The orthopedic tissues in these studies included 23 osteochondral (29.5%), 16 bone (20.5%), 13 cartilage (16.7%), 6 bone-tendon-bone (7.7%), and 12 tendon/ligaments (15.4%) with 8 (10.2%) of the studies specifically in menisci. Methods used to reduce immune response include freezing, irrigation, and immunosuppressant administration. Recorded histological evidence of immune response included cell apoptosis, type II collagen increase, IL secretion, and increased lymphocytes/plasma cells in the synovial fluid. The pathways proposed were mismatched in cell surface proteins as many studies conducted MHC class I matching, which reduced the immune response. Despite histological evidence, including HLA sensitization after transplant signaling an immune response, clinical significance was not observed. Recent clinical experience of increased MRI signal response to orthopedic allografts, along with patient symptoms, has raised questions about rejection. Clinical rejection reports are limited in this review. This immune response to orthopedic allografts must be considered and additional studies are needed to explore the relationship between rejection and clinical outcomes. This scoping review informs that there is a range of human and animal studies demonstrating various immunologic response presentations and severities with different orthopedic tissue allografts.
View details for DOI 10.1016/j.jisako.2025.101002
View details for PubMedID 40998173
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Pediatric Meniscotibial Ligament Complex Anatomy and Biomechanics.
Orthopaedic journal of sports medicine
2025; 13 (9): 23259671251367060
Abstract
Meniscal repair is increasingly performed in pediatric patients, with capsular-based techniques remaining the gold standard despite limitations such as high failure rates and risk of meniscal extrusion. Recent studies highlight the potential role of accessory knee ligaments in improving meniscal stability and repair outcomes. The meniscotibial ligament complex (MTLC) has emerged as a potential area of interest to produce more normal anatomic and biomechanical meniscal function in meniscal repair.To evaluate the native anatomy and biomechanical strength of the MTLC of the medial and lateral meniscus of pediatric knees.Descriptive laboratory study.Fourteen fresh-frozen pediatric human knees (mean age, 7.5 years; range, 5-10 years; 6 male, 8 female) were used in this study. The depth of the recess between the MTLC and the meniscocapsular complex was measured. Subsequently, the medial and lateral menisci were divided into approximate thirds, creating anterior, central, and posterior testing zones for each meniscus. Each meniscus/MTLC complex underwent monotonic load-to-failure testing on an Instron 5944 test frame with a 2-kN load cell with load applied superiorly. Biomechanical properties were analyzed using linear mixed models with donor as a random factor and aspect (medial/lateral) and position (anterior/central/posterior) as fixed factors.The posterior recess depth was significantly larger (mean, 5.4 mm; 95% CI, 4.6-6.3 mm) than anterior (mean, 3.4 mm; 95% CI, 2.6-4.2 mm) (P = .049). Maximal load to failure in the posterior MTLC (mean, 93.5 N; 95% CI, 80.0-107.0 N) was significantly higher than anterior (mean, 69.2 N; 95% CI, 56.7-81.7 N) (P = .01).This study defines a clear space in which the MTLC is distinct from the joint capsule, which is deepest in the posterior third of the medial and lateral meniscus. Our results demonstrate that the posterior region of the MTLC can withstand higher loads than the anterior region in pediatric knees.These findings offer foundational insights into the native anatomy and biomechanics of the MTLC, guiding future studies involving the MTLC in meniscal repair. This knowledge may be particularly relevant to ramp lesions, other posterior meniscal tear patterns, and meniscal transplants.
View details for DOI 10.1177/23259671251367060
View details for PubMedID 40949534
View details for PubMedCentralID PMC12426389
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Suture Anchor Fixation of the Pediatric Posteromedial and Posterolateral Menisco-Tibial Ligament Complex Matches or Exceeds Native Tissue Strength: A Cadaveric Study.
Journal of ISAKOS : joint disorders & orthopaedic sports medicine
2025: 100385
Abstract
To compare the biomechanical strength and stiffness of the native posteromedial and posterolateral meniscotibial ligament complex (MTLC) to suture anchor repair of the MTLC.Biomechanical testing was performed on 24 fresh-frozen pediatric human knees. Four conditions were tested: native posteromedial MTLC (n=14), native posterolateral MTLC (n=14), posteromedial MTLC repair (n=5), and posterolateral MTLC repair (n=5). Load-to-failure and stiffness were measured for all conditions.The load-to-failure for the posteromedial suture anchor construct was significantly higher than the native MTLC (p < 0.01). The posterolateral suture anchor construct had a significantly greater stiffness than the native MTLC (p = 0.03). Posterolateral MTLC load-to-failure and posteromedial MTLC stiffness were similar between native tissue and suture-anchor repair. All native MTLC failed at the meniscus-MTLC interface. The suture anchor groups had various failure modes, including suture pullout and breakage.Suture anchor fixation can match or exceed the native tissue's load-to-failure. This study supports the viability of suture anchor-based posterior MTLC repairs of the medial and lateral meniscus in pediatric bone.
View details for DOI 10.1016/j.jisako.2025.100385
View details for PubMedID 39798603
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Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
SCIENCE IMMUNOLOGY
2024; 9 (94): eadh2334
Abstract
T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.
View details for DOI 10.1126/sciimmunol.adh2334
View details for Web of Science ID 001209051800002
View details for PubMedID 38669316
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Screws or Sutures? A Pediatric Cadaveric Study of Tibial Spine Fracture Repairs.
The American journal of sports medicine
2023: 3635465231181059
Abstract
Tibial spine fractures are common in the pediatric population because of the biomechanical properties of children's subchondral epiphyseal bone. Most studies in porcine or adult human bone suggest that suture fixation performs better than screw fixation, but these tissues may be poor surrogates for pediatric bone. No previous study has evaluated fixation methods in human pediatric knees.To quantify the biomechanical properties of 2-screw and 2-suture repair of tibial spine fracture in human pediatric knees.Controlled laboratory study.Cadaveric specimens were randomly assigned to either 2-screw or 2-suture fixation. A standardized Meyers-Mckeever type 3 tibial spine fracture was induced. Screw-fixation fractures were reduced with two 4.0-mm cannulated screws and washers. Suture-fixation fractures were reduced by passing 2 No. 2 FiberWire sutures through the fracture fragment and the base of the anterior cruciate ligament. Sutures were secured through bony tunnels over a 1-cm tibial cortical bridge. Each specimen was mounted at 30° of flexion. A cyclic loading protocol was applied to each specimen, followed by a load-to-failure test. Outcome measures were ultimate failure load, stiffness, and fixation elongation.Twelve matched pediatric cadaveric knees were tested. Repair groups had identical mean (8.3 years) and median (8.5 years) ages and an identical number of samples of each laterality. Ultimate failure load did not significantly differ between screw (mean ± SD, 143.52 ± 41.9 7 N) and suture (135.35 ± 47.94 N) fixations (P = .760). Screws demonstrated increased stiffness and decreased elongation, although neither result was statistically significant at the .05 level (21.79 vs 13.83 N/mm and 5.02 vs 8.46 mm; P = .076 and P = .069, respectively).Screw fixation and suture fixation of tibial spine fractures in human pediatric tissue were biomechanically comparable.Suture fixations are not biomechanically superior to screw fixations in pediatric bone. Pediatric bone fails at lower loads, and in different modes, compared with adult cadaveric bone and porcine bone. Further investigation into optimal repair is warranted, including techniques that may reduce suture pullout and "cheese-wiring" through softer pediatric bone. This study provides new biomechanical data regarding the properties of different fixation types in pediatric tibial spine fractures to inform clinical management of these injuries.
View details for DOI 10.1177/03635465231181059
View details for PubMedID 37382335