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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 Mg2+ (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.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 561 - 574
10 Aug 2022
Schulze-Tanzil GG Delgado Cáceres M Stange R Wildemann B Docheva D

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1075 - 1081
17 Dec 2021
Suthar A Yukata K Azuma Y Suetomi Y Yamazaki K Seki K Sakai T Fujii H

Aims

This study aimed to investigate the relationship between changes in patellar height and clinical outcomes at a mean follow-up of 7.7 years (5 to 10) after fixed-bearing posterior-stabilized total knee arthroplasty (PS-TKA).

Methods

We retrospectively evaluated knee radiographs of 165 knees, which underwent fixed-bearing PS-TKA with patella resurfacing. The incidence of patella baja and changes in patellar height over a minimum of five years of follow-up were determined using Insall-Salvati ratio (ISR) measurement. We examined whether patella baja (ISR < 0.8) at final follow-up affected clinical outcomes, knee joint range of motion (ROM), and Knee Society Score (KSS). We also assessed inter- and intrarater reliability of ISR measurements and focused on the relationship between patellar height reduction beyond measurement error and clinical outcomes.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 704 - 713
1 Nov 2021
Zhang H Li J Xiang X Zhou B Zhao C Wei Q Sun Y Chen J Lai B Luo Z Li A

Aims

Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

Methods

OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 857 - 869
1 Dec 2020
Slullitel PA Coutu D Buttaro MA Beaule PE Grammatopoulos G

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells.

Cite this article: Bone Joint Res 2020;9(12):857–869.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1331 - 1340
3 Oct 2020
Attard V Li CY Self A Mann DA Borthwick LA O’Connor P Deehan DJ Kalson NS

Aims

Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

Methods

Well-functioning primary TKAs (n = 11), failed non-fibrotic TKAs (n = 5), and patients with a clinical diagnosis of fibrosis1 (n = 8) underwent an MRI scan with advanced metal suppression (Slice Encoding for Metal Artefact Correction, SEMAC) with gadolinium contrast. Fibrotic tissue (low intensity on T1 and T2, low-moderate post-contrast enhancement) was quantified (presence and tissue thickness) in six compartments: supra/infrapatella, medial/lateral gutters, and posterior medial/lateral.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 601 - 612
1 Sep 2020
Rajagopal K Ramesh S Walter NM Arora A Katti DS Madhuri V

Aims

Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Methods

Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.


Bone & Joint Research
Vol. 8, Issue 12 | Pages 582 - 592
1 Dec 2019
Sansone V Applefield RC De Luca P Pecoraro V Gianola S Pascale W Pascale V

Aims

The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice.

Methods

A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported.


Bone & Joint 360
Vol. 7, Issue 6 | Pages 2 - 8
1 Dec 2018
Murray IR Safran MR LaPrade RF


Bone & Joint Research
Vol. 7, Issue 3 | Pages 213 - 222
1 Mar 2018
Tang X Teng S Petri M Krettek C Liu C Jagodzinski M

Objectives

The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo.

Methods

Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents.


The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 483 - 488
1 Apr 2017
Pinsornsak P Nangnual S Boontanapibul K

Aims

Multimodal infiltration of local anaesthetic provides effective control of pain in patients undergoing total knee arthroplasty (TKA). There is little information about the added benefits of posterior capsular infiltration (PCI) using different combinations of local anaesthetic agents. Our aim was to investigate the effectiveness of the control of pain using multimodal infiltration with and without infiltration of the posterior capsule of the knee.

Patients and Methods

In a double-blind, randomised controlled trial of patients scheduled for unilateral primary TKA, 86 were assigned to be treated with multimodal infiltration with (Group I) or without (Group II) PCI. Routine associated analgesia included the use of bupivacaine, morphine, ketorolac and epinephrine. All patients had spinal anaesthesia and patient-controlled analgesia (PCA) post-operatively. A visual analogue scale (VAS) for pain and the use of morphine were recorded 24 hours post-operatively. Side effects of the infiltration, blood loss, and length of stay in hospital were recorded.


The Bone & Joint Journal
Vol. 95-B, Issue 10 | Pages 1425 - 1431
1 Oct 2013
Hardes J Henrichs MP Gosheger G Gebert C Höll S Dieckmann R Hauschild G Streitbürger A

We evaluated the clinical results and complications after extra-articular resection of the distal femur and/or proximal tibia and reconstruction with a tumour endoprosthesis (MUTARS) in 59 patients (mean age 33 years (11 to 74)) with malignant bone or soft-tissue tumours. According to a Kaplan–Meier analysis, limb survival was 76% (95% confidence interval (CI) 64.1 to 88.5) after a mean follow-up of 4.7 years (one month to 17 years). Peri-prosthetic infection was the most common indication for subsequent amputation (eight patients). Survival of the prosthesis without revision was 48% (95% CI 34.8 to 62.0) at two years and 25% (95% CI 11.1 to 39.9) at five years post-operatively. Failure of the prosthesis was due to deep infection in 22 patients (37%), aseptic loosening in ten patients (17%), and peri-prosthetic fracture in six patients (10%). Wear of the bearings made a minor revision necessary in 12 patients (20%). The mean Musculoskeletal Tumor Society score was 23 (10 to 29). An extensor lag > 10° was noted in ten patients (17%).

These results suggest that limb salvage after extra-articular resection with a tumour prosthesis can achieve good functional results in most patients, although the rates of complications and subsequent amputation are higher than in patients treated with intra-articular resection.

Cite this article: Bone Joint J 2013;95-B:1425–31.


Bone & Joint 360
Vol. 1, Issue 4 | Pages 12 - 15
1 Aug 2012

The August 2012 Knee Roundup360 looks at: meniscal defects and a polyurethane scaffold; which is best between a single or double bundle; OA of the knee; how to resolve anterior knee pain; whether yoga can be bad for your menisci; metal ions in the serum; whether ACI is any good; the ACL; whether hyaluronic acid delays collagen degradation; and hyaluronan and patellar tendinopathy.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 642 - 647
1 May 2012
Mullaji A Lingaraju AP Shetty GM

We retrospectively reviewed the records of 1150 computer-assisted total knee replacements and analysed the clinical and radiological outcomes of 45 knees that had arthritis with a pre-operative recurvatum deformity. The mean pre-operative hyperextension deformity of 11° (6° to 15°), as measured by navigation at the start of the operation, improved to a mean flexion deformity of 3.1° (0° to 7°) post-operatively. A total of 41 knees (91%) were managed using inserts ≤ 12.5 mm thick, and none had mediolateral laxity > 2 mm from a mechanical axis of 0° at the end of the surgery. At a mean follow-up of 26.4 months (13 to 48) there was significant improvement in the mean Knee Society, Oxford knee and Western Ontario and McMaster Universities Osteoarthritis Index scores compared with the pre-operative values. The mean knee flexion improved from 105° (80° to 125°) pre-operatively to 131° (120° to 145°), and none of the limbs had recurrent recurvatum.

These early results show that total knee replacement using computer navigation and an algorithmic approach for arthritic knees with a recurvatum deformity can give excellent radiological and functional outcomes without recurrent deformity.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1054 - 1059
1 Aug 2011
van Jonbergen HPW Scholtes VAB van Kampen A Poolman RW

The efficacy of circumpatellar electrocautery in reducing the incidence of post-operative anterior knee pain is unknown. We conducted a single-centre, outcome-assessor and patient-blinded, parallel-group, randomised, controlled trial to compare circumpatellar electrocautery with no electrocautery in total knee replacement in the absence of patellar resurfacing. Patients requiring knee replacement for primary osteoarthritis were randomly assigned circumpatellar electrocautery (intervention group) or no electrocautery (control group). The primary outcome measure was the incidence of anterior knee pain. A secondary measure was the standardised clinical and patient-reported outcomes determined by the American Knee Society scores and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. A total of 131 knees received circumpatellar electrocautery and 131 had no electrocautery.

The overall incidence of anterior knee pain at follow-up at one year was 26% (20% to 31%), with 19% (12% to 26%) in the intervention group and 32% (24% to 40%) in the control group (p = 0.02). The relative risk reduction from electrocautery was 40% (9% to 61%) and the number needed to treat was 7.7 (4.3 to 41.4). The intervention group had a better mean total WOMAC score at follow-up at one year compared with the control group (16.3 (0 to 77.7) versus 21.6 (0 to 76.7), p = 0.04). The mean post-operative American Knee Society knee scores and function scores were similar in the intervention and control groups (knee score: 92.4 (55 to 100) versus 90.4 (51 to 100), respectively (p = 0.14); function score: 86.5 (15 to 100) versus 84.5 (30 to 100), respectively (p = 0.49)).

Our study suggests that in the absence of patellar resurfacing electrocautery around the margin of the patella improves the outcome of total knee replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1392 - 1400
1 Oct 2008
Hayashi R Kondo E Tohyama H Saito T Yasuda K

We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks.

The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022).

The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 43 - 49
1 Jan 2008
Smith AJ Wood DJ Li M

We have examined the differences in clinical outcome of total knee replacement (TKR) with and without patellar resurfacing in a prospective, randomised study of 181 osteoarthritic knees in 142 patients using the Profix total knee system which has a femoral component with features considered to be anatomical and a domed patellar implant.

The procedures were carried out between February 1998 and November 2002. A total of 159 TKRs in 142 patients were available for review at a mean of four years (3 to 7). The patients and the clinical evaluator were blinded in this prospective study. Evaluation was undertaken annually by an independent observer using the knee pain scale and the Knee Society clinical rating system. Specific evaluation of anterior knee pain, stair-climbing and rising from a seated to a standing position was also undertaken.

No benefit was shown of TKR with patellar resurfacing over that without resurfacing with respect to any of the measured outcomes. In 22 of 73 knees (30.1%) with and 18 of 86 knees (20.9%) without patellar resurfacing there was some degree of anterior knee pain (p = 0.183). No revisions related to the patellofemoral joint were performed in either group. Only one TKR in each group underwent a re-operation related to the patellofemoral joint. A significant association between knee flexion contracture and anterior knee pain was observed in those knees with patellar resurfacing (p = 0.006).


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1165 - 1171
1 Sep 2007
Gohil S Annear PO Breidahl W

Animal studies have shown that implanted anterior cruciate ligament (ACL) grafts initially undergo a process of revascularisation prior to remodelling, ultimately increasing mechanical strength. We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans. We undertook a randomised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-strand hamstring tendon grafts. Randomised by the use of sealed envelopes, 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method. Three patients were excluded from the study. All patients underwent MR scanning postoperatively at 2, 6 and 12 months, together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee (IKDC) evaluation. All observations were made by investigators blinded to the surgical technique. Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament.

Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months (paired t-test, p = 0.002). There was a significant reduction of mid-substance signal six months after the minimal debridement technique (paired t-test, p = 0.00007). No statistically significant differences were found in tunnel placement, incidence of Cyclops lesions, blood loss, IKDC scores, range of movement or Lachman test between the two groups.