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

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. Results. T2DM rats had higher mean osteoarthritis scores than the control rats in each of the four areas that were analysed. However, only the results at the medial and lateral femur and medial tibia were significant. Cysts were also found in T2DM rats at the junction of the articular cartilage and subchondral bone. Immunohistochemical analysis does not show an increase in collagen II between control and T2DM rats. Mass comparisons also showed a significant relationship between mass and osteoarthritis score. Conclusions. T2DM was found to cause global degeneration in the UCD rat knee joints, suggesting that diabetes itself is a factor in the onset and progression of osteoarthritis. The immunohistochemistry stains showed little to no change in collagen II degeneration between T2DM and control rats. Overall, it seems that the animal model used is pertinent to future studies of T2DM in the development and progression of osteoarthritis. Cite this article: Bone Joint Res 2014;3:203–11

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. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

Objective . Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint. Methods. A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. . Results. From the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections. Conclusion. The results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies. Cite this article: Bone Joint Res 2015;4:1–5

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. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8

Objectives. To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. Methods. Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. Results. Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 . sd. 1.7, T: mean 4.5 . sd. 0.5, p = 0.14; eight weeks, S: mean 5.8 . sd. 0.8, T: mean 4.8 . sd. 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 . sd. 1.2, T: mean 4.8 . sd. 0.4, p = 0.43; eight weeks, S: mean 5.3 . sd. 0.8,T: mean 5.5 . sd. 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 . sd. 9.0N and 13.1 . sd. 5.6N) or eight weeks (12.6 . sd. 3.6N and 17.1 . sd. 6.4N, respectively). Conclusion. Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods. Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327–335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2

Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be successfully delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices in to clinical use. One approach is to follow a stepwise strategy, with the first step of seeking clearance for a temporary UHMWPE spacer containing gentamicin sulfate. In this study, we explored the effect of gentamicin sulfate (GS) content in UHMWPE on GS elution rate and antimicrobial activity against methicillin-sensitive S. aureus(MSSA). We also assessed the effect of spacer fabrication on the activity of gentamicin sulfate. We prepared and consolidated UHMWPE/GS blends in varying concentrations. After consolidation, we fabricated test samples with surface area (350mm2) to volume (300mm3) ratio of 1.2 for elution in 1.5ml phosphate buffered saline at body temperature for up to six months and quantified eluted GS content using liquid chromatography – mass spectrometry (LCMS). We assessed the antibacterial activity of the obtained samples in vitro against various concentrations of MSSA (103–106 CFU/ml). Furthermore, we quantified the probability of bacterial colonization of UHMWPE impregnated with GS compared to GS containing bone cement. We assessed any detectable changes in activity of eluted GS caused by spacer fabrication by screening m/z peaks of GS isomers in mass spectra obtained from LC-MS. Gentamicin sulfate activity was not compromised by the elevated temperature and pressure used during spacer fabrication. Elution rate of GS increased with increasing GS content in the blends studied. At comparable elution rates, the GS-loaded UHMWPE was either equivalent or better in terms of antibacterial and anticolonization properties when compared with gentamicin containing bone cement. GS-impregnated UHMWPE is a promising material for temporary spacers

Introduction. Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation, or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices to clinical use. Last year, at this meeting, we presented the preliminary pre-clinical testing for a temporary UHMWPE spacer containing gentamicin sulfate as a first step towards clinical use. Since then, we carried out a survey among the Knee Society membership about their preference for spacer use in two-stage revision surgery and found that 43% prefer to use a CoCr femoral component on an all-poly cemented tibial insert, 22% prefer bone cement spacers molded in the OR, 20% prefer static bone cement spacers, and 14% prefer pre-formed bone cement spacers. We modified our implant design based on the majority's preference for a total knee system, rather than bone cement spacers, in the temporary two-stage approach. In this study, we explored the effect of gentamicin sulfate (GS) elution from UHMWPE/GS tibial inserts on bacterial colonization on CoCr surfaces. Methods. We characterized the gentamicin sulfate (GS) particles with scanning electron microscopy (SEM). We molded UHMWPE/GS powder blends and characterized the morphology using SEM and Energy Dispersive X-Ray Spectroscopy (EDS). We submerged samples of molded UHMWPE/GS in buffered phosphate solution (PBS) at 37°C and quantified the extent of GS elution into PBS with a method described by Gubernator et al. using o-phthaladehyde (OPA) [1]. Under basic conditions, OPA reacts with primary amino groups to form fluorescent complexes. Since gentamicin is the only source of such amino acids in our elution samples, the number of fluorescent complexes formed is directly proportional to the amount of gentamicin in the sample. Using this method, we could quantify gentamicin elution by measuring sample fluorescence post OPA-reaction. We used a plate reader to excite the fluorescent complexes formed in the OPA reaction and measured the resulting emission at wavelengths of 340 nm and 455 nm, respectively. We also quantified the effect of the standard cleaning protocol (heated sonication in alkaline water and alcohol) used to clean UHMWPE implants on subsequent GS elution from UHMWPE/GS samples using the OPA method. We used agar diffusion tests to characterize antibacterial properties of UHMWPE/GS samples after cleaning. For these tests, we collected eluents collected from UHMWPE/GS and gentamicin-impregnated bone cement (BC/GS) following 1, 2, 3, and 4 weeks of elution, and tested against S. aureus (ATCC 12600). We used the “daughter cells” method developed by Bechert et al. to assess anticolonizing properties of UHMWPE/GS [2,3]. We also characterized the colonization of bacteria on CoCr surfaces in the presence of GS eluting from UHMWPE/GS test samples. For this we modified a Pin-on-Disc (PoD) wear tester: An UHMWPE/GS pin and UHMWPE pin (control) articulated against an implant-finish CoCr disc with Tryptic Soy Broth containing S. Aureus as the lubricant. After 18 hrs, we rinsed the articular surfaces of the pin and disc and stamped them onto Agar gel to transfer any adherent bacteria. We incubated the Agar plate overnight such that adherent bacteria proliferated and became visible. Results. SEM characterized the GS particles as hollow spheres (Fig 1a). These formed small groups of agglomerated domains at the virgin resin boundaries of UHMWPE after molding (Fig 1b). Sulfur signature from the EDS analysis identified the agglomerated domains as GS particles (Fig 2). Elution of GS started with an initial burst and was followed by steady elution up to 12 weeks (Fig 3). Cleaning reduced the initial burst GS elution; and the elution remained unchanged after 2 days (Fig 4). The agar diffusion test showed simmilar inhibition zones for the eluents collected from UHMWPE/GS and BC/GS, suggesting that these samples yield similar antibacterial activity against S. aureus (Fig 5). UHMWPE/GS demonstrated pronounced anticolonizing properties, effectively mitigating the proliferation of S. aureus “daughter” cells. Anticolonizing activity of Palacos R+G was not significantly different when compared with UHMWPE/GS. The PoD test showed little-to-no colonization of CoCr surfaces in the presence of UHMWPE/GS pins, indicative of excellent antibacterial properties of UHMWPE/GS against S. aureus. Conclusion. SEM and EDS has allowed us to visualize domains of gentamicin sulfate particles in UHMWPE. Our OPA method has greater precision than traditional agar-well diffusion methods of measuring gentamicin concentration and showed that gentamicin sulfate-loaded UHMWPE elutes at the same rate as Palacos R+G. Pin-on-disc experiments and the daughter cell method both confirmed that these two materials have similar anticolonization abilities. We also found that using the standard cleaning protocol for UHMWPE orthopedic implants decreased the burst of gentamicin eluting from UHMWPE, but after 2 days, it had no effect compared to uncleaned UHMWPE/GS. Finally, we found that UHMWPE/GS can reduce the colonization of bacteria on CoCr. UHMWPE/GS continues to be a promising material for treating PJI. For figures, tables, or references, please contact authors directly

Hyaline cartilage defects are a significant clinical problem for which a plethora of cartilage repair techniques are used. One such technique is cartilage replacement therapy using autologous chondrocyte or mesenchymal stem cell (MSC) implantation (ACI). Mesenchymal stem cells are increasingly being used for these types of repair technique because they are relatively easy to obtain and can be expanded to generate millions of cells. However, implanted MSCs can terminally differentiate and produce osteogenic tissue which is highly undesirable, also, MSCs generally only produce fibrocartilage which does not make biomechanically resilient repair tissue, an attribute that is crucial in high weight-bearing areas. Tissue-specific adult stem cells would be ideal candidates to fill the void, and as we have shown previously in animal model systems [Dowthwaite et al, 2004, J Cell Sci 117;889], they can be expanded to generate hundreds of millions of cells, produce hyaline cartilage and they have a restricted differential potential. Articular chondroprogenitors do not readily terminally differentiate down the osteogenic lineage. At present, research focused on isolating tissue-specific stem cells from articular cartilage has met with modest success. Our results demonstrate that using differential adhesion it is possible to easily isolate articular cartilage progenitor populations from human hyaline cartilage and that these cells can be subsequently expanded in vitro to a high population doubling whilst maintaining a normal karyotype. Articular cartilage progenitors maintain telomerase activity and telomere length that are a characteristic of progenitor/stem cells and differentiate to produce hyaline cartilage. In conclusion, we propose the identification and characterisation of a novel articular cartilage progenitor population, resident in human cartilage, which will greatly benefit future cell-based cartilage repair therapies

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.

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.

Aims

Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Aims

Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

Aims

Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia.

Aims

Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes.

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.

Aims

Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy.

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.

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.

Aims

The aim of this study was to evaluate the surface damage, the density of crosslinking, and oxidation in retrieved antioxidant-stabilized highly crosslinked polyethylene (A-XLPE) tibial inserts from total knee arthroplasty (TKA), and to compare the results with a matched cohort of standard remelted highly crosslinked polyethylene (XLPE) inserts.