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1.
Connect Tissue Res ; 64(2): 175-185, 2023 03.
Article in English | MEDLINE | ID: mdl-36318110

ABSTRACT

OBJECTIVE: Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model. METHODS: Adult female Lewis rats were randomized to noninvasive ACLR or Sham. Two weeks post-injury, contrast-enhanced micro-computed tomography (µCT) of femoral and patellar cartilage was performed using 20% v/v ioxaglate. Morphometric parameters of femoral trochlear and patellar cartilage, subchondral bone, and trabecular bone were derived from µCT. Sagittal Safranin-O/Fast-Green-stained histologic sections were graded using the OARSI score in a blinded fashion. RESULTS: Cartilage and bone remodelling consistent with an early PTOA phenotype were observed in both femoral trochleas and patellae. ACLR caused osteophyte formation of the patella and pathology in the superficial zone of articular cartilage, including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering. There were significant increases in thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to patellar and trochlear trabecular microarchitecture, were indicative of catabolic bone remodelling. Several injury-induced changes, including increased cartilage thickness and trabecular spacing and decreased trabecular number were more severe in the patella compared to the trochlea. CONCLUSION: The patellofemoral joint develops mild but evident pathology in the early period following ACL rupture, extending the utility of this model to the study of patellofemoral PTOA.


Subject(s)
Anterior Cruciate Ligament Injuries , Cartilage, Articular , Osteoarthritis , Animals , Female , Rats , Anterior Cruciate Ligament/pathology , Anterior Cruciate Ligament Injuries/complications , Anterior Cruciate Ligament Injuries/pathology , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Osteoarthritis/pathology , Rats, Inbred Lew , X-Ray Microtomography/adverse effects
2.
Nanomaterials (Basel) ; 11(3)2021 Feb 26.
Article in English | MEDLINE | ID: mdl-33652733

ABSTRACT

Orthopedic implants requiring osseointegration are often surface modified; however, implants may shed these coatings and generate wear debris leading to complications. Titanium nanotubes (TiNT), a new surface treatment, may promote osseointegration. In this study, in vitro (rat marrow-derived bone marrow cell attachment and morphology) and in vivo (rat model of intramedullary fixation) experiments characterized local and systemic responses of two TiNT surface morphologies, aligned and trabecular, via animal and remote organ weight, metal ion, hematologic, and nondecalcified histologic analyses. In vitro experiments showed total adherent cells on trabecular and aligned TiNT surfaces were greater than control at 30 min and 4 h, and cells were smaller in diameter and more eccentric. Control animals gained more weight, on average; however, no animals met the institutional trigger for weight loss. No hematologic parameters (complete blood count with differential) were significantly different for TiNT groups vs. control. Inductively coupled plasma mass spectrometry (ICP-MS) showed greater aluminum levels in the lungs of the trabecular TiNT group than in those of the controls. Histologic analysis demonstrated no inflammatory infiltrate, cytotoxic, or necrotic conditions in proximity of K-wires. There were significantly fewer eosinophils/basophils and neutrophils in the distal region of trabecular TiNT-implanted femora; and, in the midshaft of aligned TiNT-implanted femora, there were significantly fewer foreign body giant/multinucleated cells and neutrophils, indicating a decreased immune response in aligned TiNT-implanted femora compared to controls.

3.
J Orthop Res ; 39(9): 1965-1976, 2021 09.
Article in English | MEDLINE | ID: mdl-33146410

ABSTRACT

Assess acute alterations in bone turnover, microstructure, and histomorphometry following noninvasive anterior cruciate ligament rupture (ACLR). Twelve female Lewis rats were randomized to receive noninvasive ACLR or Sham loading (n = 6/group). In vivo µCT was performed at 3, 7, 10, and 14 days postinjury to quantify compartment-dependent subchondral (SCB) and epiphyseal trabecular bone remodeling. Near-infrared (NIR) molecular imaging was used to measure in vivo bone anabolism (800 CW BoneTag) and catabolism (Cat K 680 FAST). Metaphyseal bone remodeling and articular cartilage morphology was quantified using ex vivo µCT and contrast-enhanced µCT, respectively. Calcein-based dynamic histomorphometry was used to quantify bone formation. OARSI scoring was used to assess joint degeneration, and osteoclast number was quantified on TRAP stained-sections. ACLR induced acute catabolic bone remodeling in subchondral, epiphyseal, and metaphyseal compartments. Thinning of medial femoral condyle (MFC) SCB was observed as early as 7 days postinjury, while lateral femoral condyles (LFCs) exhibited SCB gains. Trabecular thinning was observed in MFC epiphyseal bone, with minimal changes to LFC. NIR imaging demonstrated immediate and sustained reduction of bone anabolism (~15%-20%), and a ~32% increase in bone catabolism at 14 days, compared to contralateral limbs. These findings were corroborated by reduced bone formation rate and increased osteoclast numbers, observed histologically. ACLR-injured femora had significantly elevated OARSI score, cartilage thickness, and cartilage surface deviation. ACL rupture induces immediate and sustained reduction of bone anabolism and overactivation of bone catabolism, with mild-to-moderate articular cartilage damage at 14 days postinjury.


Subject(s)
Anterior Cruciate Ligament Injuries , Cartilage, Articular , Musculoskeletal Diseases , Osteoarthritis , Animals , Anterior Cruciate Ligament Injuries/complications , Anterior Cruciate Ligament Injuries/pathology , Bone Remodeling , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Female , Musculoskeletal Diseases/pathology , Osteoarthritis/pathology , Rats , Rats, Inbred Lew
4.
NPJ Regen Med ; 5: 3, 2020.
Article in English | MEDLINE | ID: mdl-32133156

ABSTRACT

Therapeutic approaches requiring the intravenous injection of autologous or allogeneic mesenchymal stromal cells (MSCs) are currently being evaluated for treatment of a range of diseases, including orthopaedic injuries. An alternative approach would be to mobilise endogenous MSCs into the blood, thereby reducing costs and obviating regulatory and technical hurdles associated with development of cell therapies. However, pharmacological tools for MSC mobilisation are currently lacking. Here we show that ß3 adrenergic agonists (ß3AR) in combination with a CXCR4 antagonist, AMD3100/Plerixafor, can mobilise MSCs into the blood in mice and rats. Mechanistically we show that reversal of the CXCL12 gradient across the bone marrow endothelium and local generation of endocannabinoids may both play a role in this process. Using a spine fusion model we provide evidence that this pharmacological strategy for MSC mobilisation enhances bone formation.

5.
J Biomed Mater Res B Appl Biomater ; 108(4): 1483-1493, 2020 05.
Article in English | MEDLINE | ID: mdl-31692221

ABSTRACT

As total joint replacements increase annually, new strategies to attain solid bone-implant fixation are needed to increase implant survivorship. This study evaluated two morphologies of titania nanotubes (TiNT) in in vitro experiments and an in vivo rodent model of intramedullary fixation, to simulate joint arthroplasty conditions. TiNT surfaces were prepared via an electrochemical etching process, resulting in two different TiNT morphologies, an aligned structure with nanotubes in parallel and a trabecular bone-like structure. in vitro data showed bone marrow cell differentiation into osteoblasts as well as osteoblastic phenotypic behavior through 21 days. In vivo, both TiNT morphologies generated greater bone formation and bone-implant contact than control at 12 weeks, as indicated by µCT analyses and histology, respectively. TiNT groups also exhibited greater strength of fixation compared to controls, when subjected to wire pull-out testing. TiNT may be a promising surface modification for promoting osseointegration.


Subject(s)
Bone-Anchored Prosthesis , Cancellous Bone , Nanotubes , Osseointegration , Osteogenesis , Titanium , Animals , Cancellous Bone/injuries , Cancellous Bone/metabolism , Cancellous Bone/pathology , Female , Rats , Rats, Sprague-Dawley
6.
Orthopedics ; 41(3): e376-e382, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29570765

ABSTRACT

Fresh allograft transplantation of osteochondral defects restores functional articular cartilage and subchondral bone; however, rapid loss of chondrocyte viability during storage and osteoclast-mediated bone resorption at the graft-host interface after transplantation negatively impact outcomes. The authors present a pilot study evaluating the in vitro and in vivo impact of augmenting storage media with bisphosphonates. Forty cylindrical osteochondral cores were harvested from femoral condyles of human cadaveric specimens and immersed in either standard storage media or storage media supplemented with nitrogenated or non-nitrogenated bisphosphonates. Maintenance of graft structure and chondrocyte viability were assessed at 3 time points. A miniature swine trochlear defect model was used to evaluate the influence of bisphosphonate-augmented storage media on in vivo incorporation of fresh osteochondral tissue, which was quantified via µCT and decalcified histology. In the in vitro study, Safranin-O/Fast Green staining showed that both low- and high-dose nitrogenated-treated grafts retained chondrocyte viability and cartilage matrix for up to 43 days of storage. Allografts stored in nitrogenated-augmented storage media showed both µCT and histologic evidence of enhanced in vivo bony and cartilaginous incorporation in the miniature swine trochlear defect model. Several preclinical studies have shown the potential for enhanced storage of fresh osteochondral allografts via additions of relatively common drugs and biomolecules. This study showed that supplementing standard storage media with nitrogenated bisphosphonates may improve maintenance of chondrocyte viability and graft structure during cold storage as well as enhance in vivo osseous and cartilaginous incorporation of the graft. [Orthopedics: 2018; 41(3):e376-e382.].


Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Transplantation , Chondrocytes/drug effects , Diphosphonates/pharmacology , Femur/drug effects , Osseointegration/drug effects , Tissue Preservation/methods , Allografts/drug effects , Allografts/physiology , Animals , Cell Survival/drug effects , Chondrocytes/transplantation , Female , Femur/transplantation , Humans , In Vitro Techniques , Male , Outcome Assessment, Health Care , Pilot Projects , Random Allocation , Swine , Transplantation, Homologous
7.
Foot Ankle Int ; 37(9): 958-67, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27272267

ABSTRACT

BACKGROUND: Fresh osteochondral allografting of the talus is one treatment option for large chondral defects. Following positive early term results, failure rates of up to 35% have been reported. A retrieval study was performed to characterize failed talar allografts. METHODS: Failed fresh osteochondral allografts of the talus were retrieved on revision. Cases of deep infection were excluded. After tissue fixation, samples were decalcified, embedded, and stained with Safranin-O/Fast Green, osteocalcin, tumor necrosis factor alpha (TNF-α), CD4, CD8, and CD68. Slides were graded according to the modified Mankin scoring system or severity scale. Medical record review was performed. RESULTS: Eight allografts (7 patients) were retrieved from patients, following an average term of implantation of 31 months (range, 12-58). There were 3 types of allografts in this series (hemidome, n=5; segmental, n=2; bipolar, n=1). Reasons for transplantation were post-traumatic arthritis or osteonecrosis; reasons for revision were graft failure/collapse, nonunion, progressive arthritis, and/or pain. Prior to revision, all grafts exhibited collapse and subchondral lucencies. At the graft host interface, Safranin-O staining demonstrated substantial loss of sulfated glycosaminoglycans, Osteocalcin immunostaning was nearly absent, CD68 (indicating osteoclast activity) was predominantly exhibited, and CD4+ helper T cells as well as CD8+ cytotoxic T cells and NK cells-cell types commonly implicated in allogeneic organ transplant rejection-were found in high concentrations. TNF-α was present throughout the graft. CONCLUSION: A histopathologic analysis of 8 retrieved, failed talar allografts was performed. Graft failure appeared to be primarily biologic, with an extensive loss of viable cartilaginous and osseous tissue at the graft-host interface. This study provides the first evidence of a potential CD4+ and CD8+ lymphocyte-mediated failure mechanism in fresh osteochondral allografts that were revised following collapse. LEVEL OF EVIDENCE: Level IV, case series.


Subject(s)
Allografts/physiopathology , Bone Transplantation/methods , Cartilage Diseases/pathology , Cartilage, Articular/pathology , Osteonecrosis/surgery , Talus/surgery , Transplantation, Homologous/methods , Follow-Up Studies , Humans , Osteonecrosis/physiopathology , Prospective Studies
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