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Bone & Joint Research
Vol. 3, Issue 2 | Pages 20 - 31
1 Feb 2014
Kiapour AM Murray MM

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair. Cite this article: Bone Joint Res 2014;3:20–31


Objectives. The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage. Methods. Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored. Results. The CBA group showed similar results to the autologous group in biomechanical properties, Moran’s criteria, histological tests and Wakitani histological scoring. Conclusions. These results suggest that tissue-engineered cartilage constructed using the CBA technique could be used effectively to repair cartilage defects in the weight-bearing area of joints. Cite this article: H. Lin, J. Zhou, L. Cao, H. R. Wang, J. Dong, Z. R. Chen. Tissue-engineered cartilage constructed by a biotin-conjugated anti-CD44 avidin binding technique for the repairing of cartilage defects in the weight-bearing area of knee joints in pigs. Bone Joint Res 2017;6:–295. DOI: 10.1302/2046-3758.65.BJR-2016-0277


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Methods

The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 294 - 300
1 Jul 2016
Nishioka H Nakamura E Hirose J Okamoto N Yamabe S Mizuta H

Objectives. The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping. Methods. Coronal T1ρ and T2 mapping and three-dimensional gradient-echo images were obtained from 20 subjects with medial knee osteoarthritis. We set the regions of interest (ROIs) on the full-thickness cartilage of the medial femoral condyle (MFC) and medial tibial plateau (MTP) of the knee and measured the cartilage thickness (mm) and T1ρ and T2 relaxation times (ms). Statistical analysis of time-dependent changes in the cartilage thickness and the T1ρ and T2 relaxation times was performed using one-way analysis of variance, and Scheffe’s test was employed for post hoc multiple comparison. Results. The cartilage-like repair tissue appeared on the cartilage surface of the medial compartment post-operatively, and the cartilage thickness showed a significant increase between the pre-operative and one-year post-operative time points (MFC; p = 0.003, MTP; p < 0.001). The T1ρ values of the cartilage-like repair tissue showed no difference over time, however, the T2 values showed a significant decrease between the pre-operative and one-year post-operative time points (MFC; p = 0.004, MTP; p = 0.040). Conclusion. This study clarified that the fibrocartilage-like repair tissue appeared on the articular surface of the medial compartment after HCO as evidenced by MRI T1ρ and T2 mapping. Cite this article: H. Nishioka, E. Nakamura, J. Hirose, N. Okamoto, S. Yamabe, H. Mizuta. MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy. Bone Joint Res 2016;5:294–300. DOI: 10.1302/2046-3758.57.BJR-2016-0057.R1


Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


Bone & Joint Research
Vol. 10, Issue 4 | Pages 269 - 276
1 Apr 2021
Matsubara N Nakasa T Ishikawa M Tamura T Adachi N

Aims

Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect.

Methods

A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.


Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Methods

Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system.


Bone & Joint Research
Vol. 8, Issue 12 | Pages 593 - 600
1 Dec 2019
Koh Y Lee J Lee H Kim H Chung H Kang K

Aims

Commonly performed unicompartmental knee arthroplasty (UKA) is not designed for the lateral compartment. Additionally, the anatomical medial and lateral tibial plateaus have asymmetrical geometries, with a slightly dished medial plateau and a convex lateral plateau. Therefore, this study aims to investigate the native knee kinematics with respect to the tibial insert design corresponding to the lateral femoral component.

Methods

Subject-specific finite element models were developed with tibiofemoral (TF) and patellofemoral joints for one female and four male subjects. Three different TF conformity designs were applied. Flat, convex, and conforming tibial insert designs were applied to the identical femoral component. A deep knee bend was considered as the loading condition, and the kinematic preservation in the native knee was investigated.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 31 - 42
1 Jan 2017
Kang K Koh Y Jung M Nam J Son J Lee Y Kim S Kim S

Objectives

The aim of the current study was to analyse the effects of posterior cruciate ligament (PCL) deficiency on forces of the posterolateral corner structure and on tibiofemoral (TF) and patellofemoral (PF) contact force under dynamic-loading conditions.

Methods

A subject-specific knee model was validated using a passive flexion experiment, electromyography data, muscle activation, and previous experimental studies. The simulation was performed on the musculoskeletal models with and without PCL deficiency using a novel force-dependent kinematics method under gait- and squat-loading conditions, followed by probabilistic analysis for material uncertain to be considered.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 89 - 94
1 Apr 2014
Cook JL Hung CT Kuroki K Stoker AM Cook CR Pfeiffer FM Sherman SL Stannard JP

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair.

Cite this article: Bone Joint Res 2014;4:89–94.


Bone & Joint Research
Vol. 4, Issue 6 | Pages 93 - 98
1 Jun 2015
Smith NA Achten J Parsons N Wright D Parkinson B Thompson P Hutchinson CE Spalding T Costa ML

Objectives

Subtotal or total meniscectomy in the medial or lateral compartment of the knee results in a high risk of future osteoarthritis. Meniscal allograft transplantation has been performed for over thirty years with the scientifically plausible hypothesis that it functions in a similar way to a native meniscus. It is thought that a meniscal allograft transplant has a chondroprotective effect, reducing symptoms and the long-term risk of osteoarthritis. However, this hypothesis has never been tested in a high-quality study on human participants. This study aims to address this shortfall by performing a pilot randomised controlled trial within the context of a comprehensive cohort study design.

Methods

Patients will be randomised to receive either meniscal transplant or a non-operative, personalised knee therapy program. MRIs will be performed every four months for one year. The primary endpoint is the mean change in cartilage volume in the weight-bearing area of the knee at one year post intervention. Secondary outcome measures include the mean change in cartilage thickness, T2 maps, patient-reported outcome measures, health economics assessment and complications.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 203 - 211
1 Jun 2014
Onur T Wu R Metz L Dang A

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

Methods

T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis.


Bone & Joint Research
Vol. 2, Issue 2 | Pages 18 - 25
1 Feb 2013
Kon E Filardo G Di Matteo B Perdisa F Marcacci M

Objectives

Matrix-assisted autologous chondrocyte transplantation (MACT) has been developed and applied in the clinical practice in the last decade to overcome most of the disadvantages of the first generation procedures. The purpose of this systematic review is to document and analyse the available literature on the results of MACT in the treatment of chondral and osteochondral lesions of the knee.

Methods

All studies published in English addressing MACT procedures were identified, including those that fulfilled the following criteria: 1) level I-IV evidence, 2) measures of functional or clinical outcome, 3) outcome related to cartilage lesions of the knee cartilage.


Bone & Joint Research
Vol. 2, Issue 4 | Pages 70 - 78
1 Apr 2013
Hamilton DF McLeish JA Gaston P Simpson AHRW

Objectives

Lower limb muscle power is thought to influence outcome following total knee replacement (TKR). Post-operative deficits in muscle strength are commonly reported, although not explained. We hypothesised that post-operative recovery of lower limb muscle power would be influenced by the number of satellite cells in the quadriceps muscle at time of surgery.

Methods

Biopsies were obtained from 29 patients undergoing TKR. Power output was assessed pre-operatively and at six and 26 weeks post-operatively with a Leg Extensor Power Rig and data were scaled for body weight. Satellite cell content was assessed in two separate analyses, the first cohort (n = 18) using immunohistochemistry and the second (n = 11) by a new quantitative polymerase chain reaction (q-PCR) protocol for Pax-7 (generic satellite cell marker) and Neural Cell Adhesion Molecule (NCAM; marker of activated cells).


Bone & Joint Research
Vol. 3, Issue 3 | Pages 82 - 88
1 Mar 2014
Abdel MP Morrey ME Barlow JD Grill DE Kolbert CP An KN Steinmann SP Morrey BF Sanchez-Sotelo J

Objectives

The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model.

Methods

A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 238 - 244
1 Oct 2012
Naraoka T Ishibashi Y Tsuda E Yamamoto Y Kusumi T Kakizaki I Toh S

Objectives

This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation.

Methods

Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3).


Bone & Joint Research
Vol. 1, Issue 10 | Pages 234 - 237
1 Oct 2012
Hughes AW Dwyer AJ Govindaswamy R Lankester B

Objectives

Our aim was to assess the use of intra-operative fluoroscopy in the assessment of the position of the tibial tunnel during reconstruction of the anterior cruciate ligament (ACL).

Methods

Between January and June 2009 a total of 31 arthroscopic hamstring ACL reconstructions were performed. Intra-operative fluoroscopy was introduced (when available) to verify the position of the guidewire before tunnel reaming. It was only available for use in 20 cases, due to other demands on the radiology department. The tourniquet times were compared between the two groups and all cases where radiological images lead to re-positioning of the guide wire were recorded. The secondary outcome involved assessing the tibial interference screw position measured on post-operative radiographs and comparing with the known tunnel position as shown on intra-operative fluoroscopic images.