Journal of Orthopaedic Research®最新文献

{"title":"The Human ACL Sheath Exhibits Distinct Transcriptomic Signatures and Functional Properties.","authors":"James Rogot, Jennifer A Kunes, Kurt S Holuba, Roshan P Shah, Christopher S Ahmad, Stavros Thomopoulos, Clark T Hung, Beth G Ashinsky","doi":"10.1002/jor.70271","DOIUrl":"10.1002/jor.70271","url":null,"abstract":"<p><p>The anterior cruciate ligament (ACL) has poor intrinsic healing capacity due to exposure to the intra-articular synovial environment of the knee. Therefore, tendon auto- or allograft reconstruction is the mainstay of treatment for a torn ACL. Following reconstruction, there is a high rate of post-traumatic osteoarthritis, likely due to alteration of joint biomechanics, which supports the clinical need to advance primary ACL repair strategies. The ACL is enclosed by a vascularized, synovial-like sheath (ACL-s), which supplies nutrients to the central core (ACL-c). The ACL-s may act as a selective barrier to solute diffusion, protecting the ACL-c from damaging synovial enzymes and/or hyaluronic acid, while allowing nutrient diffusion. Like the synovium, the ACL-s is rich with collagens and resident macrophages, thus may be susceptible to change of function following injury and inflammation. We investigated the healthy and inflammed ACL-s structure, diffusivity, and cellular profile in comparison to the ACL-c and synovium to guide the development and optimization of primary repair technologies. Diffusion and histologic assessments revealed the ACL-s functions as a semi-permeable barrier through lower solute diffusivity and unique collagen organization. RNAseq demonstrated differential expression of extracellular matrix, inflammatory, and immune-related genes across ACL-s, ACL-c, and synovium, with the ACL-s uniquely showing upregulated expression of CX3CR1 and CLDN5 suggestive of an immunologic barrier. This study establishes the potential of the ACL-s to serve an immunologic and functional barrier that protects the underlying ACL-c from the inflammatory milieu following injury, and therefore, should be recapitulated when developing primary ACL repair technologies.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 9","pages":"e70271"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPOT: An Early Detection Tool for Predicting Pain Trajectories Following Intra-Articular Injections.","authors":"Brittany L Nelson, Prathap Jayaram, Scott D Boden, Kenneth Mautner, Michael B Gottschalk, Gregory D Myer, Hicham Drissi, Jed A Diekfuss","doi":"10.1002/jor.70270","DOIUrl":"10.1002/jor.70270","url":null,"abstract":"<p><p>The purpose of this study was to identify 12-month postinjection knee osteoarthritis (KOA) pain trajectories and develop an early prediction model using patient-reported pain scores. Data were derived from a multi-site, single-blind randomized controlled trial of intra-articular injections for KOA. The primary analysis focused on participants assigned to autologous bone marrow aspirate concentrate, umbilical cord tissue-derived mesenchymal stromal cells, or stromal vascular fraction. After data-quality screening, the primary trajectory cohort included 317 participants and the prediction cohort included 295 participants with Screening and Month-3 KOOS-12 Pain scores. Latent class mixed-effects modeling identified a two-class solution selected for clinical interpretability: 66.6% of patients followed an Improved Pain trajectory and 33.4% followed a Persistent Pain trajectory. Although a three-class model had slightly lower BIC, the additional class included only 2.5% of participants and was not retained for the clinical prediction tool. A logistic regression model using KOOS-12 Pain at Screening and 3-month change predicted trajectory membership with AUC = 0.785 in training and AUC = 0.792 in the held-out test set. A training-selected threshold of 0.656 yielded held-out test sensitivity = 0.790, specificity = 0.692, PPV = 0.860, NPV = 0.581, and accuracy = 0.761. The resultant model was implemented as the Symptom Prediction for Outcomes of Treatment (SPOT) web calculator. Clinical Significance: The SPOT web calculator only requires KOOS-12 Pain data from Screening and Month 3 to classify patients as likely to follow an Improved Pain vs. Persistent Pain trajectory after orthobiologic KOA treatment. Trial Registration: ClinicalTrials.gov identifier: NCT03818737.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 9","pages":"e70270"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lanthionine Ketenamine Derivative Enhances Early Functional Recovery Following Skeletal Muscle Ischemia-Reperfusion Injury Through Modulation of Autophagy and Oxidative Stress","authors":"Valentina Barrera,&nbsp;Jose H. Treviño III,&nbsp;Travis T. Denton,&nbsp;Blake B. Rasmussen,&nbsp;Christopher Rathbone,&nbsp;Yulieth Soto,&nbsp;Maria A. Gonzalez Porras,&nbsp;Hugo Giambini","doi":"10.1002/jor.70269","DOIUrl":"10.1002/jor.70269","url":null,"abstract":"<p>Ischemia-reperfusion injury (IRI) induces skeletal muscle damage through oxidative stress, impaired autophagy, and satellite cell (SC) dysfunction, ultimately compromising regenerative capacity and functional recovery. We investigated whether the naturally occurring autophagy-stimulating compound 2-<i>n</i>-hexyl lanthionine ketenamine phosphonate (2-<i>n</i>-hexyl LKE-P) enhances SC resilience and promotes early regenerative responses following IRI. Primary SCs isolated from Sprague Dawley rats (96% Pax-7+ purity) were treated with 2-<i>n</i>-hexyl LKE-P or rapamycin. Autophagic flux was assessed using CYTO-ID flow cytometry and Western blot analysis of LC3-I and LC3-II, and viability was assessed under baseline and hydrogen peroxide (H₂O₂)-induced oxidative stress conditions. In parallel, a proof-of-concept hindlimb IRI model (3-h tourniquet) evaluated early functional recovery and transcriptional changes. In vitro, 2-<i>n</i>-hexyl LKE-P significantly increased autophagy flux and enhanced SC viability across concentrations and treatment durations, whereas rapamycin reduced proliferation. Under 500 µM H₂O₂, which decreased viability by ~63%, 2-<i>n</i>-hexyl LKE-P restored cell survival toward control levels, demonstrating robust protection against oxidative stress. In vivo, treated animals demonstrated improved grip strength recovery between days 2 and 7 post-injury compared to PBS-treated controls. Molecular analyzes revealed significant upregulation of autophagy regulators (Beclin-1, ULK-1) and antioxidant marker SOD-1, with coordinated upward trends in additional autophagy (ATG-7, LC3, p62) and myogenic genes (MyoG, MHC). Collectively, these findings suggest that 2-<i>n</i>-hexyl LKE-P enhances SC survival by modulating autophagy and reinforcing antioxidant defenses, resulting in improved early functional recovery following IRI. These results identify 2-<i>n</i>-hexyl LKE-P modulation of autophagy and oxidative stress as a promising therapeutic strategy for limiting IRI-induced skeletal muscle damage.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing Overlooked Variables in Preclinical Fracture Repair Research for Improved Translation","authors":"Christina Capobianco,&nbsp;Katharina Schmidt-Bleek,&nbsp;Melanie Haffner-Luntzer,&nbsp;Chelsea Bahney,&nbsp;Joseph L. Roberts,&nbsp;Matthew J. Silva,&nbsp;Annemarie Lang","doi":"10.1002/jor.70268","DOIUrl":"10.1002/jor.70268","url":null,"abstract":"<p>In preclinical research focused on bone fracture repair, a significant gap exists in understanding and incorporating key variables that influence homeostasis and pathophysiological processes. Factors such as immune system responses, sex differences, pain and innervation, and microbiota are often overlooked. Preclinical studies frequently rely on rodent models housed under sterile, specific pathogen-free conditions, resulting in naïve immune responses. Additionally, these studies typically use only one sex, fail to monitor stress behaviors, and do not assess infections or commensal microorganisms. While such controlled approaches enable the study of essential mechanisms, they may hinder the successful translation of findings to immunocompetent and diverse human populations, who do not live in sterile environments and vary widely in biological sex, gender, age, immune history, and living conditions. Here, we summarize the material presented at the Preclinical Models Section and International Section of Fracture Repair Workshop held during the 2026 Orthopaedic Research Society (ORS) Annual Meeting in Charlotte, North Carolina.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Wear Behavior of Titanium Nitride-Coated Titanium and Cobalt Chromium Femoral Components in Cementless Total Knee Arthroplasty","authors":"Harold I. Salmons,&nbsp;Kailey Fitzgerald,&nbsp;Sally LiArno,&nbsp;Behzad Farshid,&nbsp;Geoffrey H. Westrich","doi":"10.1002/jor.70266","DOIUrl":"10.1002/jor.70266","url":null,"abstract":"<div>\u0000 \u0000 <p>Femoral component surface roughness is a critical determinant of polyethylene wear in total knee arthroplasty (TKA). Titanium nitride (TiN) ceramic surface coatings have been developed to improve wear resistance and address concerns related to metal hypersensitivity; however, comprehensive wear data remain limited. This knee simulator study evaluated the performance of TiN-coated titanium alloy (6 wt% aluminum, 4 wt% vanadium, balance titanium, Ti-6Al-4V) substrate femoral components compared with cobalt chromium (CoCr) femoral components. Mode I wear testing was conducted for 5.0 million cycles (mc) using highly crosslinked polyethylene tibial inserts, with wear rates and polyethylene debris morphology quantified. Mode III third-body abrasive wear testing was performed on TiN-coated femoral components using embedded 500 µm TiN-coated particles for 3.0 mc. Surface roughness was measured using White Light Interferometry (arithmetic mean height, Sa), and surface integrity was assessed using scanning electron microscopy. Following 5.0 mc of Mode I wear, volumetric wear rates were equivalent between TiN-coated and CoCr femoral components (1.03 vs 1.04 mm³/million cycles; <i>p</i> = 0.001), with no notable differences in polyethylene particle size (<i>p</i> = 0.114) or morphology. During third-body testing, surface scratching of the TiN coating was observed without evidence of gross surface failure. As anticipated, the mean Sa of TiN-coated femoral components increased through 3.0 mc of Mode III third-body testing, while remaining lower than literature-reported retrieved CoCr values (<i>p</i> = 0.001). In conclusion, TiN-coated femoral components demonstrated comparable in vitro adhesive wear performance to CoCr and provided improved resistance to abrasive conditions, where long-term resistance to abrasion is expected to govern reduced wear.</p>\u0000 </div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Preclinical Rat Model of Acute Compartment Syndrome","authors":"Sishu Guan,&nbsp;Xingchen Lu,&nbsp;Chang Liu,&nbsp;Yi Zhang,&nbsp;Yang Li,&nbsp;Hui Zhao,&nbsp;Lianyang Zhang","doi":"10.1002/jor.70262","DOIUrl":"10.1002/jor.70262","url":null,"abstract":"<p>Acute compartment syndrome (ACS) is common in trauma, challenging early diagnosis and treatment. An accurate ACS model is vital for its management. Most prior animal models have induced intrafascial hypertension by exogenous interventions, focusing on the study of secondary injury post-ACS formation. A novel rat model with spontaneous ACS formation after trauma was constructed, emphasizing early onset and development. The 300-mmHg pressure simulated by a blood pressure cuff was applied to rat hindlimbs for 3 h. A balloon catheter connected to a manometer was developed, and intracompartmental pressure (ICP) and blood perfusion were measured continuously for 2 h. H&amp;E staining and serum index were detected at 0, 1-, 2-, 3-, and 8-h postinjury. The results showed injured hindlimbs swelled, with ICP rising continuously, reaching 30 mmHg in 35 min, peaking at 60–80 min before entering a plateau period, effectively reproducing ACS pressure evolution. The blood perfusion showed a three-step change, negatively correlating with ICP &gt; 30 mmHg. Muscle tissues presented typical time-dependent pathological changes, with progressive myofibrillar rupture, inflammatory cell infiltration, and increases in serum IL-1β, TNF-α, CK, and BUN over time. This study successfully established a new preclinical ACS-like rat model. Compared with previous studies, the ICP in the hindlimbs in this study was spontaneously elevated after crush, leading to secondary injury. Furthermore, a new manometric catheter device was developed to enable continuous monitoring of ICP without repeated fluid injections. The constructed animal model is closer to the clinic, and it lays a solid foundation for ACS pathogenesis.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cells From Human Exfoliated Deciduous Teeth as a Potent Cell Therapy for Radiation-Induced Osteonecrosis Model","authors":"Toshifumi Murakami,&nbsp;Noritaka Fukuda,&nbsp;Ryo Fujita,&nbsp;Hideyuki Kobayashi,&nbsp;Yasuyuki Mitani,&nbsp;M. Alaa Terkawi,&nbsp;Kazuo Tomizawa,&nbsp;Norimasa Iwasaki,&nbsp;Masahiko Takahata","doi":"10.1002/jor.70263","DOIUrl":"https://doi.org/10.1002/jor.70263","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteonecrosis is a serious disorder leading to subchondral bone collapse and joint dysfunction. Osteonecrosis has been increasingly diagnosed before bone collapse; however, effective treatments for regenerating necrotic bone remain unavailable. Mesenchymal stem cell (MSC)-based therapies are promising; however, bone marrow-derived MSCs (BMSCs) are limited by donor burden, low yield, and suboptimal regenerative efficacy. Stem cells from human exfoliated deciduous teeth (SHED) exhibit higher proliferative capacity, enhanced growth factor secretion, minimal senescence, and noninvasive harvesting, making them a strong alternative. We evaluated SHED and BMSCs in a refractory rat model of radiation-induced tibial osteonecrosis. In vitro, SHED secreted similar or higher levels of proangiogenic and chemotactic factors—including vascular endothelial growth factor, angiopoietin-2, stem cell factor, monocyte chemoattractant protein-1, and C-C motif chemokine ligand 5—than BMSCs and significantly enhanced macrophage migration. Hydroxyapatite/collagen scaffolds seeded with SHED or BMSCs were transplanted into irradiated tibial bone defects in vivo. Micro-computed tomography revealed significantly accelerated bone regeneration with SHED, but not with BMSCs, compared with cell-free scaffolds. Histology confirmed new bone and marrow formation at SHED-treated sites, accompanied by increased periosteal proliferation and vascularity. Bulk RNA sequencing showed that SHED transplantation upregulated angiogenesis and immune cell recruitment–related pathways, whereas BMSCs upregulated genes associated with endochondral ossification without effective regeneration. Notably, SHED did not differentiate into osteoblasts or chondrocytes in vivo, indicating paracrine mediation of angiogenesis and macrophage recruitment. Given the limited regenerative capacity of necrotic bone, SHED's angiogenic and immunomodulatory activities position it as a promising candidate for cell-based therapy in refractory osteonecrosis.</p>\u0000 </div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Wear Simulation of a Kinematically Aligned Knee Implant Tilted at an Angle of 8°","authors":"Stefan Schroeder,&nbsp;Mareike Mueller,&nbsp;Maximilian Uhler,&nbsp;Therese Bormann,&nbsp;Sebastian Jaeger,&nbsp;Jan Philippe Kretzer","doi":"10.1002/jor.70265","DOIUrl":"https://doi.org/10.1002/jor.70265","url":null,"abstract":"<p>Despite promising results of kinematic alignment (KA), there are still concerns regarding the wear behavior of KA knee implants. In a previous study, mechanically aligned (MA), KA and malaligned (MalA) knee implants were tested in a wear simulation study using Attune knee implant systems. The results showed no increased wear rate for a mild KA (KA4°) and MalA (MalA4°) condition in comparison to MA (MA0°) knee implants. This study analyzes the wear behavior of a KA condition of 8° (KA8°). The test setup was adapted accordingly. In addition, all tests of the previous study (MA0°, MalA4° and KA4°) and the KA8° condition were replicated using PFC implant systems to indicate if the previous results can be transferred to the predecessor model of the Attune knee implant system. The KA8° using the Attune knee implant system did not lead to a higher wear rate (2.4 ± 0.1 mg/10⁶ cycles) in comparison to the wear results of the previous study (3.8 ± 0.5 mg/10⁶ cycles for MA0°; 2.7 ± 0.2 mg/10⁶ cycles for MalA4° and 4.1 ± 0.2 mg/10⁶ cycles for KA4°). The PFC implant system led to higher wear rates than the Attune implant system but showed the same trend for the different alignment methods (5.1 ± 0.4 mg/10⁶ cycles for MA0°; 3.9 ± 0.1 mg/10⁶ cycles for MalA4°, 5.1 ± 0.8 mg/10⁶ cycles for KA4° and 3.5 ± 1.0 mg/10⁶ cycles for KA8°). KA8° did not show wear related problems but further in vitro and in vivo studies are necessary.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.70265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fractures Around Collared and Collarless Hip Stems Initiate in High Strain Regions: A Combined Cadaveric Experiment and Finite Element Analysis","authors":"Ryan T. Helbock,&nbsp;Clarisse Zigan,&nbsp;Andrew Hughes,&nbsp;Joseph D. Lipman,&nbsp;Timothy M. Wright,&nbsp;Peter K. Sculco,&nbsp;Elizabeth B. Gausden,&nbsp;Sony Manandhar,&nbsp;Ghislain Maquer,&nbsp;Jeff Bischoff,&nbsp;Fernando J. Quevedo Gonzalez","doi":"10.1002/jor.70267","DOIUrl":"https://doi.org/10.1002/jor.70267","url":null,"abstract":"<div>\u0000 \u0000 <p>Periprosthetic femoral fracture (PFF) is a common early complication after primary total hip arthroplasty. Collared stems reduce but do not eliminate the incidence of PFF, and exhibit variable biomechanical effectiveness, emphasizing our limited understanding of the local bone–implant interaction mechanics. Our goal was to elucidate the relationship between the local strains at the bone–implant interface and the experimental fracture patterns and loads for collared and collarless stems.</p>\u0000 <p>Six pairs of women cadaveric femurs implanted with a collarless or collared stem were loaded to failure under simulated stumbling to determine the location of PFF and the load to fracture, which we related to the collar-calcar separation. Corresponding specimen-specific FE models were developed to determine the strain at the bone-implant interface and to predict the fracture onset load and location of fracture, which we related to the experimental location of PFF and the load-to-fracture.</p>\u0000 <p>Load to fracture was greater for collared stems and was inversely correlated with the collar-calcar separation at the time of implantation (<i>r </i>= −0.80, <i>p</i> = 0.055). Fractures occurred in areas of high strain. The experimental fracture location coincided with the first yielding cortical element in five cases. The load at which the first cortical element yielded (i.e., onset of fracture was moderately correlated with the experimental fracture load (<i>R</i>² = 0.43, RMSE = 1231 N).</p>\u0000 <p>Our results emphasize the importance of initial calcar contact to realize the benefits of the collar. Localized load transfer was a precursor of macroscopic fracture, which initiated in areas of high tensile strain.</p>\u0000 </div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decellularized Extracellular Matrix Mitigates the Senescent Phenotype and Restores Osteogenic Potential in Human Mesenchymal Stromal Cells","authors":"Connor J. Dorais,&nbsp;Nikolia M. Kruger,&nbsp;David H. Ramos-Rodriguez,&nbsp;Mark A. Lee,&nbsp;J. Kent Leach","doi":"10.1002/jor.70264","DOIUrl":"https://doi.org/10.1002/jor.70264","url":null,"abstract":"<div>\u0000 \u0000 <p>Autologous cell-based approaches for bone repair using mesenchymal stromal cells (MSCs) in older patients are limited in part by cellular senescence, resulting in impaired MSC self-renewal and differentiation. Currently, the field lacks a standardized method to induce senescence in human MSCs and characterize them for experimental use, as well as effective strategies to mitigate the harmful effects of the senescence-associated secretory phenotype (SASP). We previously demonstrated that MSC-secreted decellularized extracellular matrix (dECM) enhances the osteogenic potential and survival of MSCs. We hypothesized that senescent MSCs would exhibit improved osteogenic potential and reduced SASP activity when maintained on dECM. We first demonstrated that a senescent phenotype can be reliably induced in human MSCs through ionizing irradiation coupled with a 21-day preconditioning phase in culture, evidenced by increased beta-galactosidase staining and enlarged cell area. We then observed that senescent MSCs on dECM exhibit improved osteogenic potential and reduced SASP compared to cells on tissue culture plastic, evidenced by quantifying markers of osteogenic differentiation and ELISAs for known inflammatory cytokines. These data support the promise of dECM as an instructive biomaterial to enhance the regenerative potential of MSCs from older patients for autologous bone repair.</p></div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"44 8","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}