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The Bone & Joint Journal
Vol. 101-B, Issue 7 | Pages 824 - 831
1 Jul 2019
Mahmoud EE Adachi N Mawas AS Deie M Ochi M

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831


The Bone & Joint Journal
Vol. 97-B, Issue 12 | Pages 1628 - 1633
1 Dec 2015
Elmadag M Uzer G Yildiz F Erden T Bilsel K Büyükpinarbasili N Üsümez A Bozdag E Sen C

This animal study compares different methods of performing an osteotomy, including using an Erbium-doped Yttrium Aluminum Garnet laser, histologically, radiologically and biomechanically. A total of 24 New Zealand rabbits were divided into four groups (Group I: multihole-drilling; Group II: Gigli saw; Group III: electrical saw blade and Group IV: laser). A proximal transverse diaphyseal osteotomy was performed on the right tibias of the rabbits after the application of a circular external fixator. The rabbits were killed six weeks after the procedure, the operated tibias were resected and radiographs taken. . The specimens were tested biomechanically using three-point bending forces, and four tibias from each group were examined histologically. Outcome parameters were the biomechanical stability of the tibias as assessed by the failure to load and radiographic and histological examination of the osteotomy site. . The osteotomies healed in all specimens both radiographically and histologically. The differences in the mean radiographic (p = 0.568) and histological (p = 0.71) scores, and in the mean failure loads (p = 0.180) were not statistically significant between the groups. . Different methods of performing an osteotomy give similar quality of union. The laser osteotomy, which is not widely used in orthopaedics is an alternative to the current methods. Cite this article: Bone Joint J 2015;97-B:1628–33


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims. Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function. Materials and Methods. A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6). Results. At eight weeks, FiberTape alone or FiberTape-augmented autograft demonstrated increased biomechanical stability compared with autograft regarding ultimate load to failure (p = 0.035), elongation (p = 0.006), and energy absorption (p = 0.022). FiberTape-grafted samples also demonstrated increased bone mineral density in the bone tunnel (p = 0.039). Histological evaluation showed integration of all grafts in the bone tunnels by new bone formation, and limited signs of inflammation overall. A lack of prolonged inflammation in all samples was confirmed by quantification of inflammation biomarkers. However, no regeneration of ligament-like tissue was observed along the suture tape materials. Except for one autograft failure, no adverse events were detected. Conclusion. Our results indicate that FiberTape increases the biomechanical performance of intra-articular ligament reconstructions in a verified rabbit model at eight weeks. Within this period, FiberTape did not adversely affect bone tunnel healing or invoke a prolonged elevation in inflammation. Cite this article: Bone Joint J 2019;101-B:1238–1247


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 880 - 887
1 Aug 2023
Onodera T Momma D Matsuoka M Kondo E Suzuki K Inoue M Higano M Iwasaki N

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Methods

A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations.


We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft–bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL–bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft. Cite this article: Bone Joint J 2013;95-B:923–8


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 924 - 932
1 Jul 2015
Lee MC Ha C Elmallah RK Cherian JJ Cho JJ Kim TW Bin S Mont MA

The aim of this study was to assess the effect of injecting genetically engineered chondrocytes expressing transforming growth factor beta 1 (TGF-β1) into the knees of patients with osteoarthritis. We assessed the resultant function, pain and quality of life.

A total of 54 patients (20 men, 34 women) who had a mean age of 58 years (50 to 66) were blinded and randomised (1:1) to receive a single injection of the active treatment or a placebo. We assessed post-treatment function, pain severity, physical function, quality of life and the incidence of treatment-associated adverse events. Patients were followed at four, 12 and 24 weeks after injection.

At final follow-up the treatment group had a significantly greater improvement in the mean International Knee Documentation Committee score than the placebo group (16 points; -18 to 49, vs 8 points; -4 to 37, respectively; p = 0.03). The treatment group also had a significantly improved mean visual analogue score at final follow-up (-25; -85 to 34, vs -11 points; -51 to 25, respectively; p = 0.032). Both cohorts showed an improvement in Western Ontario and McMaster Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome Scores, but these differences were not statistically significant. One patient had an anaphylactic reaction to the preservation medium, but recovered within 24 hours. All other adverse events were localised and resolved without further action.

This technique may result in improved clinical outcomes, with the aim of slowing the degenerative process, leading to improvements in pain and function. However, imaging and direct observational studies are needed to verify cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing.

Cite this article: Bone Joint J 2015;97-B:924–32.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 205 - 209
1 Feb 2012
Kadonishi Y Deie M Takata T Ochi M

We examined whether enamel matrix derivative (EMD) could improve healing of the tendon–bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon–bone interface was filled with 40 µl of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon–bone interface (p = 0.047), whereas the control group had few fibres and the tendon–bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon–bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon–bone repair in ACL reconstruction.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 62 - 67
1 Jan 2012
Aurich M Hofmann GO Mückley T Mollenhauer J Rolauffs B

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 59 - 64
1 Jan 2014
Weston-Simons JS Pandit H Kendrick BJL Jenkins C Barker K Dodd CAF Murray DW

Mobile-bearing unicompartmental knee replacements (UKRs) with a flat tibial plateau have not performed well in the lateral compartment, owing to a high dislocation rate. This led to the development of the Domed Lateral Oxford UKR (Domed OUKR) with a biconcave bearing. The aim of this study was to assess the survival and clinical outcomes of the Domed OUKR in a large patient cohort in the medium term.

We prospectively evaluated 265 consecutive knees with isolated disease of the lateral compartment and a mean age at surgery of 64 years (32 to 90). At a mean follow-up of four years (sd 2.2, (0.5 to 8.3)) the mean Oxford knee score was 40 out of 48 (sd 7.4). A total of 12 knees (4.5%) had re-operations, of which four (1.5%) were for dislocation. All dislocations occurred in the first two years. Two (0.8%) were secondary to significant trauma that resulted in ruptured ligaments, and two (0.8%) were spontaneous. In four patients (1.5%) the UKR was converted to a primary TKR. Survival at eight years, with failure defined as any revision, was 92.1% (95% confidence interval 81.3 to 100).

The Domed Lateral OUKR gives good clinical outcomes, low re-operation and revision rates and a low dislocation rate in patients with isolated lateral compartmental disease, in the hands of the designer surgeons.

Cite this article: Bone Joint J 2014;96-B:59–64.


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 301 - 304
1 Mar 2013
Brennan SA Devitt BM O’Neill CJ Nicholson P

Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed.

Cite this article: Bone Joint J 2013;95-B:301–4.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 601 - 603
1 May 2009
Townshend D Emmerson K Jones S Partington P Muller S

The administration of intra-articular local anaesthetic is common following arthroscopy of the knee. However, recent evidence has suggested that bupivacaine may be harmful to articular cartilage. This study aimed to establish whether infiltration of bupivacaine around the portals is as effective as intra-articular injection.

We randomised 137 patients to receive either 20 ml 0.5% bupivacaine introduced into the joint (group 1) or 20 ml 0.5% bupivacaine infiltrated only around the portals (group 2) following arthroscopy. A visual analogue scale was administered one hour post-operatively to assess pain relief. Both patients and observers were blinded to the treatment group. A power calculation was performed.

The mean visual analogue score was 3.24 (sd 2.20) in group I and 3.04 (sd 2.31) in group 2. This difference was not statistically significant (p = 0.62).

Infiltration of bupivacaine around the portals had an equivalent effect on pain scores at one hour, and we would therefore recommend this technique to avoid the possible chondrotoxic effect of intra-articular bupivacaine.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 8 | Pages 1027 - 1031
1 Aug 2006
Karim A Pandit H Murray J Wandless F Thomas NP

We sought to determine whether smoking affected the outcome of reconstruction of the anterior cruciate ligament. We analysed the results of 66 smokers (group 1 with a mean follow-up of 5.67 years (1.1 to 12.7)) and 238 non-smokers (group 2 with a mean follow-up of 6.61 years (1.2 to 11.5)), who were statistically similar in age, gender, graft type, fixation and associated meniscal and chondral pathology. The assessment was performed using the International Knee Documentation Committee form and serial cruciometer readings.

Poor outcomes were reported in group 1 for the mean subjective International Knee Documentation Committee score (p < 0.001), the frequency (p = 0.005) and intensity (p = 0.005) of pain, a side-to-side difference in knee laxity (p = 0.001) and the use of a four-strand hamstring graft (p = 0.015). Patients in group 1 were also less likely to return to their original level of pre-injury sport (p = 0.003) and had an overall worse final 7 International Knee Documentation Committee grade score (p = 0.007).

Despite the well-known negative effects of smoking on tissue healing, the association with an inferior outcome after reconstruction of the anterior cruciate ligament has not previously been described and should be included in the pre-operative counselling of patients undergoing the procedure.