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.

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Aims

The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate.

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. Previous studies suggested that the regenerative activity of stem cells can be enhanced by exposure to tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells-derived mesenchymal-like progenitors (hiPSCs-MPs) can enhance the regenerative potential of human bone marrow mesenchymal stromal cells (hBMSCs). ECM was engineered from hiPSC-MPs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. hBMSCs were cultured on the engineered ECM, and differentiated into osteogenic, chondrogenic and adipogenic lineages. Growth and differentiation responses were compared to tissue culture plastic controls. Decellularization of ECM resulted in efficient cell elimination, as observed in our previous studies. Cultivation hBMSCs on the ECM in osteogenic medium significantly increased hBMSC growth, collagen deposition and alkaline phosphatase activity. Furthermore, expression of osteogenic genes and matrix mineralization were significantly higher compared to plastic controls. Chondrogenic micromass culture on the ECM significantly increased cell growth and expression of chondrogenic markers, including glycosaminoglycans and collagen type II. Adipogenic differentiation of hBMSCs on the ECM resulted in significantly increased hBMSC growth, but significantly reduced lipid vacuole deposition compared to plastic controls. Together, our studies suggest that BMSCs differentiation into osteogenic and chondrogenic lineages can be enhanced, whereas adipogenic activity is decreased by the culture on engineered ECM. Contribution of specific matrix components and underlying mechanisms need to be further elucidated. Our studies suggest that the three-lineage differentiation of aged BMSCs can be modulated by culture on hiPSC-engineered ECM. Further studies are aimed at scaling-up to three-dimensional ECM constructs for osteochondral tissue regeneration

Aims

Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage.

Aims

Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA).

Aims

The STRYDE nail is an evolution of the PRECICE Intramedullary Limb Lengthening System, with unique features regarding its composition. It is designed for load bearing throughout treatment in order to improve patient experience and outcomes and allow for simultaneous bilateral lower limb lengthening. The literature published to date is limited regarding outcomes and potential problems. We report on our early experience and raise awareness for the potential of adverse effects from this device.

The course of secondary fracture healing typically consists of four major phases including inflammation, soft and hard callus formation, and bone remodeling. Callus formation is promoted by mechanical stimulation, yet little is known about the healing tissue response to strain stimuli over shorter timeframes on hourly and daily basis. The aim of this study was to explore the hourly, daily and weekly variations in bone healing progression and to analyze the short-term response of the repair tissue to well-controlled mechanical stimulation. A system for continuous monitoring of fracture healing was designed for implantation in sheep tibia. The experimental model was adapted from Tufekci et al. 2018 and consisted of 3 mm transverse osteotomy and 30 mm bone defect resulting in an intermediate mobile bone fragment in the tibial shaft. Whereas the distal and proximal parts of the tibia were fixed with external fixator, the mobile fragment was connected to the proximal part via a second, active fixator. A linear actuator embedded in the active fixator moved the mobile fragment axially, thus stimulating mechanically the tissue in the osteotomy gap via well-controlled displacement being independent from the sheep's functional weightbearing. A load sensor was integrated in the active fixation to measure the force acting in the osteotomy gap. During each stimulation cycle the displacement and force magnitudes were recorded to determine in vivo fracture stiffness. Following approval of the local ethics committee, experiments were conducted on four skeletally mature sheep. Starting from the first day after surgery, the daily stimulation protocols consisted of 1000 loading events equally distributed over 12 hours from 9:00 to 21:00 resulting in a single loading event every 44 seconds. No stimulation was performed overnight. One animal had to be excluded due to inconsistencies in the load sensor data. The onset of tissue stiffening was detected around the eleventh day post-op. However, on a daily basis, the stiffness was not steadily increasing, but instead, an abrupt drop was observed in the beginning of the daily stimulations. Following this initial drop, the stiffness increased until the last stimulation cycle of the day. The continuous measurements enabled resolving the tissue response to strain stimuli over hours and days. The presented data contributes to the understanding of the influence of patient activity on daily variations in tissue stiffness and can serve to optimize rehabilitation protocols post fractures

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Aims

Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

Aims

To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements.

Introduction. The combined incidence of anatomic (aTSA) and reverse total shoulder arthroplasties (rTSA) in the US is 90,000 per annum and rising. There has been little attention given to potential long-term complications due to periprosthetic tissue reactions to implant debris. The shoulder has been felt to be relatively immune to these complications due to lower acting loads compared to other joint arthroplasties. In this study, retrieved aTSAs and rTSAs were examined to determine the extent of implant damage and to characterize the nature of the corresponding periprosthetic tissue responses. Methods. TSA components and periprosthetic tissues were retrieved from 23 (eleven aTSA, twelve rTSA). Damage to the implants was characterized using light microscopy. Head/stem taper junction damage was graded 1–4 as minimal, mild, moderate or marked. Damage on polyethylene (PE) and metal bearing surfaces was graded 1–3 (mild, moderate, marked). H&E stained sections of periprosthetic soft tissues were evaluated for the extent and type of cellular response. A semi-quantitative system was used to score (1=rare to 4=marked) the overall number of particle-laden macrophages, foreign body giant cells, lymphocytes, plasma cells, eosinophils, and neutrophils. Implant damage and histopathological patterns were compared between the two TSA groups using the Mann-Whitney and Spearman tests. Results. The PE bearing surfaces of aTSAs were dominated by three-body wear and plastic deformation, whereas the rTSA PE components exhibited mainly polishing and scratching. Metal surface damage occurred in a few cases of both groups. Only one aTSA case exhibited marked taper corrosion. In both groups the primary nature of the inflammatory response was a moderate to marked macrophage response to wear particles (78% of cases). The particle-laden macrophages tended to occur in broad sheets and contained metal, PE, bone cement and suture debris. The extent of macrophage and foreign body giant cell responses was greater in the aTSA group (p≤0.001). Metal particles were seen in 63% of aTSAs and 83% of rTSAs. In the aTSA group, bone cement was seen in all cases and suture was observed in 9 cases, and their presence was larger compared to the rTSA group (p≤0.022). There was no difference in the number of other cell types between the groups. A mild lymphocyte response and chromium-phosphate debris was present within the tissue of the aTSA case with marked corrosion, which may be indicative of an early stage adverse local tissue reaction (ALTR) analog to total hip replacements with taper corrosion. Conclusion. Both groups exhibited a strong macrophage response to a combination of different types of implant debris—PE, metal, bone cement and suture. The prevalence of a marked macrophage response was larger in the aTSA group which may be explained by the larger overall presence of cement and suture within this group. PE particles may differ in size between groups due to different acting wear mechanisms which may also affect the extent of the macrophage response. Although corrosion within modular junctions was overall rare, the presence of one case with marked corrosion shows that taper corrosion and subsequent ALTRs are possible in TSAs. For any figures or tables, please contact authors directly

Wear and corrosion debris generated from total hip replacements (THR) can cause adverse local tissue reactions (ALTR) or osteolysis, often leading to premature implant failure. The tissue response can be best characterized by histopathological analysis, which accurately determines the presence of cell types, but is limited in the characterization of biochemical changes (e.g. protein conformation alteration). Fourier transform infrared micro-spectroscopy imaging (FTIRI) enables rapid analysis of the chemical structure of biological tissue with a high spatial resolution, and minimal additional sample preparation. The data provides the most information through multivariate method carried out by hierarchical clustering analysis (HCA). It is the goal of this study to demonstrate the beneficial use of this multivariate approach in providing pathologist with biochemical information from cellular and subcellular organization within joint capsule tissue retrieved from THR patients. Joint capsule tissue from 2 retrieved THRs was studied. Case 1: a metal-on-polyethylene THR, and Case 2: a dual modular metal-on-metal THR. Prior to FTIRI analysis, tissue samples were formalin-fixed paraffin-embedded and 5μm thick microtome sectioned samples were prepared and mounted on BaF. 2. discs and deparaffinized. FTIRI data were collected using high-definition transmission mode (pixel size: ∼1.1 μm. 2. ). Hyperspectral images were exported to CytoSpec V2.0.06 for processing and reconstruction into pseudo-color maps based on cluster assignments. Case 1 exhibited a strong presence of lymphocytes and macrophages (Fig. 1a). Since the process of taking second derivatives reduces the half width of the spectral peaks, it increases the sensitivity toward detecting shoulders or second peaks that may not be apparent in the raw spectra (Fig. 1b). Thus, areas occupied by lymphocytes and macrophages can be easily distinguished providing a fast tissue screening method. Here, HCA was able to distinguish macrophages and lymphocytes based on the infrared response, even in areas where both occurred intermixed. (Fig. 1c) The tissue in direct proximity to cells had a slightly altered collagenous structure. Case 1 also exhibited multiple glassy, green particles which can typically observed around THRs that underwent taper corrosion (Fig. 2a). HCA image was able to visualize and distinguish large CrPO. 4. particles, embedded within fibrin exudate rich areas, collagenous tissue without inflammatory cells, and a nearby area with a strong macrophage presence and some finer CrPO. 4. particles (Fig. 2d). Moreover, this method can not only locate macrophages, but distinguish particle-laden macrophages depending the type of particles within the cells. In Case 2 (Fig. 3a), clustering results (Fig. 3 b&c) are consistent with the fact that different particle types are associated with MoM bearing surface wear (Co rich particles), corrosion of the CoCrMo taper junctions (Cr-oxides and –phosphate), fretting of Ti-alloy dual modular tapers (Ti-oxides, Ti alloy particles), and even suture debris, which all occurred in this case. Although details of debris types are not available, specifications are possible by coupling other techniques. The results demonstrate that multivariate FTIRI based spectral histopathology is a powerful tool to characterize the chemical structure and foreign body response within periprosthetic tissue, thus providing insights into the biological impact of different types of implant debris. For any figures or tables, please contact the authors directly

Aims

The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis.

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.

Objectives

This study investigated the biomechanical performance of decellularized porcine superflexor tendon (pSFT) grafts of varying diameters when utilized in conjunction with contemporary ACL graft fixation systems. This aimed to produce a range of ‘off-the-shelf’ products with predictable mechanical performance, depending on the individual requirements of the patient.

Introduction. We studied free (= local powder) tobramycin and doxycycline, and controlled release (= local lipid bilayer) doxycycline formulations in a rat model representing a generic joint infection. We . hypothesized. that evidence of infection (quantitative colony forming units (CFU), qualitative SEM, histopathology) (1a) would be reduced with local vs. systemic antibiotic, (1b) any antibiotic would be superior to control (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Methods. Study groups. included infected and non-infected (1) control, (2) systemic ceftriaxone (daily), (3) local tobramycin, (4) local doxycycline and (5) controlled release doxycycline. With IACUC approval, (10 rats/group; power =0.8), 50-μl, 10×4 CFU Staphylococcus aureus, slowly injecting into distal femoral medullary canal, reliably created joint infection. Antibiotic formulation was introduced locally into cavity and joint, pin was inserted, and tissues closed. After 4-weeks, serum, pin, bone and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on surface of pin, histopathology identified tissue response, liquid chromatography/mass spectrometry measured plasma antibiotic. Kruskal-Wallis one-way ANOVA compared groups. Results. Groups receiving antibiotic reported lower CFU/ml in synovium compared with control (no treatment) group (1b), but there was no difference between systemic, free or controlled antibiotics (1a). Different results with different antibiotics were shown, with free tobramycin reducing CFU/ml to a greater extent than free doxycycline in the synovium (2) (p<0.05). Antibiotic in plasma was nondetectable all groups (3). SEM revealed some biofilm on pin in all groups. . Limitations. include inoculation method, single observation period, administration of only one bacterial and antibiotic dose, and not including pairing local and systemic antibiotic. Conclusion. There was no difference in infection reduction nor detectable antibiotic in serum for any antibiotic formulation, but CFU's in synovium differed based on antibiotic formulation. For any tables or figures, please contact the authors directly

Aims

The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components.

Objectives. Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods. ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results. Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion. The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2