In 2019, Lin et al. published a proof-of-concept study of electrical impedance spectroscopy as a simple and low-cost method to characterize progression of fracture repair (Lin et al., Sci Rep 2019). However, the electrical impedance sensors were placed in the fracture site which may impair the transfer to clinical use. To further explore the concept of monitoring fracture healing by electrical impedance spectroscopy, we established a tibial fracture model in the rabbit where sensors are positioned in proximity to the fracture site but without being placed in the fracture site. The aim of this pilot study was to explore whether distinct patterns of electrical impedance would evolve as tibial fractures in rabbits were evaluated until radiographic signs of healing. Approval was granted from the Inspectorate of the Animal Experimentation under the Danish Ministry of Justice. Four rabbits were anaesthetized, and in each rabbit a tibial osteotomy was made and stabilized by an external fixator. Electrical impedance was measured immediately postoperative and hereafter daily until euthanization after 3 weeks. Recordings were obtained within a wide frequency range (10 Hz to 1 MHz) from an inner electrode placed into the medullary canal and an outer electrode placed extracortical on the lateral with a distance of 3 mm to the defect. A similar pattern of electrical impedance over time was observed in the four rabbits. During the very early stages of fracture healing, an initial fluctuation in electrical impedance occurred. However, after 10 days the curves revealed a steady daily increase in electrical impedance. The first radiological signs of bone healing were detected after 14 days and progressed in all four rabbits in accordance with increments in the electrical impedance until termination of the pilot study after 21 days. Consistent electrical impedance patterns were detected during bone healing in a pilot study of four rabbits. Further research is needed to explore whether the presented method of electrical impedance measurements can be used to monitor bone healing over time.
Achilles tendinopathy is classically defined as a tendinosis devoid of an inflammatory cell population. However, recent literature suggests inflammation as a mediator in the pathogenesis. These finding were mainly based on semi-quantative immunohistochemistry. We therefore used flow cytometry to obatain a more accurate identification and quantification of the different cell types involved. Thirty-two samples were obtained from twelve patients with chronic tendinopathic lesions undergoing Achilles tendon surgery. Samples obtained from three patients with hemiplegia requiring surgical release due to spastic Achilles tendons served as control. We used two panels to identify the myeloid and lymphoid population targeting the following markers: CD45, CD3, CD8, CD4, CD19, CD11b, CD56, CD14, CD16, Vα7.2, 6b11, CD161, TCRγδ. To assess the presence of fibroblasts CD90 was targeted. The mean count of CD45+ hematopoietic cells in the tendinopathic samples was significantly higher than in the control samples, respectively 13.27% and 3.24% of the total cell count (P<0.001). The mean fraction of CD3+ cells present in the complete cell population was significantly higher in pathological samples than in control samples, respectively 1.70% and 0.37% (P<0.05). Presence of CD19+ B cells was not reported. The mean fraction of γδ T cells was significantly higher in tendinopathic samples compared to blood samples of the same patient and consisted of 12.9% and 5.8% γδ T cells respectively (P<0.05). These findings support an inflammatory cell infiltration in midportion Achilles tendinopathy that show similarities to enthesitis in SpA. This implies a potential target to investigate in novel treatment modalities.
The purpose of this study was to evaluate the outcome of vascularized iliac bone grafting for idiopathic osteonecrosis of the femoral head. We reviewed the clinical and radiological results of 35 operations performed on 29 patients who had osteonecrosis of the femoral head (ONFH) in which a pedicle iliac bone grafting was performed for minimum follow-up of 10 years. The average age was 35 years (range, 17 to 62 years). According to the Japanese Orthopaedic Association classification for ONFH, there were 28 stage 2, 7 stage 3-A, 17 type C-1 hips, and 18 type C-2 hips. After a bone tunnel of 1.5 × 5 cm was made in the anterior aspect of the femoral head and curettage of necrotic lesion was performed, the pedicle bone with the deep circumflex iliac artery (DCIA) was inserted into the anterolateral portion of the femoral head. The average follow-up period was 13 years and 6 months. Weight bearing was not allowed for 2 months after the operation. Survival rate of the femoral head was calculated by Kaplan-Meier methods, and collapse of the femoral head and configuration of the femoral head was investigated at final follow-up.Introduction
Methods
Introduction. The healing of rotator cuff injuries poses significant challenges, primarily due to the complexity of recreating the native tendon-to-bone interface, characterized by highly organized structural and compositional gradients. Addressing this, our innovative approach leverages bioprinted living tissue constructs, incorporating layer-specific growth factors (GFs) to facilitate enthesis regeneration. This method aims to guide in situ zonal differentiation of stem cells, closely mirroring the natural enthesis tissue architecture. Method. Our strategy involves the utilization of advanced bioprinting technology to fabricate living tissue constructs. These constructs are meticulously designed with embedded microsphere-based delivery carriers, ensuring the sustained release of tenogenic, chondrogenic, and osteogenic growth factors. This layer-specific release mechanism is tailored to promote the precise differentiation of stem cells across different regions of the construct, aligning with the gradient nature of enthesis tissues. Result. In vitro studies demonstrated that our layer-specific tissue constructs significantly outperformed basal constructs without GFs, achieving region-specific differentiation of stem cells. More critically, in a rabbit model of rotator cuff tear, these bioprinted living tissue constructs expedited enthesis regeneration. Key outcomes included improved biomechanical properties, enhanced collagen deposition and alignment, and the formation of a gradient fibrocartilage interface with aligned collagen fibrils. After 12 weeks, the constructs achieved an ultimate load failure of 154.3 ± 9.5 N resembling that of native enthesis tissues, marking a notable achievement in tissue engineering. Conclusion. Our
Introduction. Supraspinatus tears comprise most rotator cuff injuries, the leading cause of shoulder pain and an increasing problem with ageing populations. Surgical repair of considerable or persistent damages is customary, although not invariably successful. Tissue engineering presents a promising alternative to generate functional tissue constructs with improved healing capacities. This study explores tendon tissue constructs’ culture in a platform providing physiological mechanical stimulation and reports on the effect of different loading regimes on the viability of human tendon cells. Method. Porcine decellularized tendon scaffolds were fixed into flexible, self-contained bioreactor chambers, seeded with human tenocytes, allocated in triplicates to either static control, low (15±0.8Newtons [N]), medium (26±0.5N), or high (49±2.1N)-force-regime groups, connected to a perfusion system and cultured under standard conditions. A humanoid robotic arm provided 30-minute adduction/abduction stimulation to chambers daily over a week. A metabolic activity assay served to assess cell viability at four time points. Statistical significance = p<0.05. Result. One day after beginning mechanical stimulation, chambers in the medium and high-force regimes displayed a rise in metabolic activity by 3% and 5%, respectively. By the last experimental day, all mechanical stimulation regimes had induced an augment in cell viability (15%, 57% and 39% with low, medium, and high loads, respectively) matched against the static controls. Compared to all other conditions, the medium-force regime prompted an increased relative change in metabolic activity for every time point set against day one (p<0.05). Conclusion. Human tenocytes’ viability reflected by metabolic activity in a physiologically relevant bioreactor system is enhanced by loading forces around 25N when mechanically stimulating using adduction/abduction motions. Knowing the most favourable load regime to stimulate tenocyte growth has informed the ongoing
Abstract. Objectives. Biomechanics is an essential form of measurement in the understanding of the development and progression of osteoarthritis (OA). However, the number of participants in biomechanical studies are often small and there is limited ways to share or combine data from across institutions or studies. This is essential for applying modern machine learning methods, where large, complex datasets can be used to identify patterns in the data. Using these data-driven approaches, it could be possible to better predict the optimal interventions for patients at an early stage, potentially avoiding pain and inappropriate surgery or rehabilitation. In this project we developed a prototype database platform for combining and sharing biomechanics datasets. The database includes methods for importing and standardising data and associated variables, to create a seamless, searchable combined dataset of both healthy and knee OA biomechanics. Methods. Data was curated through calls to members of the OATech Network+ (. https://www.oatechnetwork.org/. ). The requirements were 3D motion capture data from previous studies that related to analysing the biomechanics of knee OA, including participants with OA at any stage of progression plus healthy controls. As a minimum we required kinematic data of the lower limbs, plus associated kinetic data (i.e. ground reaction forces). Any additional, complementary data such as EMG could also be provided. Relevant ethical approvals had to be in place that allowed re-use of the data for other research purposes. The datasets were uploaded to a University hosted cloud platform. The database platform was developed using Javascript and hosted on a Windows server, located and managed within the department. Results. Three independent datasets were curated following the call to OATech Network+ members. These originated from separate studies collected from biomechanics labs at Cardiff University, Keele University, and Imperial College London. Participants with knee OA were at various stages of progression and all datasets included healthy controls. The total sample size of the three datasets is n=244, split approximately equally between healthy and knee OA participants. Naming conventions and formatting of the exported data varied greatly across datasets. Datasets were therefore formatted into a common format prior to upload, with guidelines developed for future contributions. Uploading data at the marker set level was too complicated for combination at the prototype stage. Therefore, processed variables relating to joint angles and joint moments were used. The resulting prototype database included an import function to align and standardise variables. A a simple query tool was further developed to extract outputs from the database, along with a suitable user interface for basic data
Introduction and Objective. Bone remodelling is a continuous process whereby osteocytes regulate the activity of osteoblasts and osteoclasts to repair loading-induced microdamage. While many in vitro studies have established the role of paracrine factors (e.g., RANKL/OPG) and cellular pathways involved in bone homeostasis, these techniques are generally limited to two-dimensional cell culture, which neglects the role of the native extracellular matrix in maintaining the phenotype of osteocyte. Recently, ex vivo models have been used to understand cell physiology and mechanobiology in the presence of the native matrix. Such approaches could be applicable to study the mechanisms of bone repair, whilst also enabling
Abstract. Objectives. Musculoskeletal injuries are the leading contributor to disability globally, yet current treatments do not offer complete restoration of the tissue. This has resulted in the
Background. Despite arthroscopy being the gold standard for long head of biceps pathology, the literature is seemingly lacking in any critical appraisal or validation to support its use. The aim of this study was to evaluate its appropriateness as a benchmark for diagnosis. The objectives were to evaluate whether the length of the tendon examined at arthroscopy allows visualisation of areas of predilection of pathology and also to determine the rates of missed diagnoses when compared to an open approach. Methods. A systematic review of cadaveric and clinical studies was performed. The search strategy was applied to Medline, PubMed and Google Scholar databases. All relevant articles were included. Critical appraisal of clinical studies was performed using a validated quality assessment scale. Results. Six articles were identified for inclusion in the review. This included both clinical and cadaveric studies. The overall population comprised 25 cadaveric specimens and 575 patients. Cadaveric studies showed that the use of a hook probe allowed arthroscopic visualisation of between 28% and 48% of the overall length of the LHB. In the clinical series the rate of missed diagnoses at arthroscopy when compared to open
The treatment of extremity ballistic injury is challenging in that the zone of injury can be extensive and determining the surgical exposure can be difficult. We describe a method of pre-operative evaluation of the zone of injury in conjunction with the regional anesthesiologist utilizing ultrasound to determine the presence of nerve disruption. This non-invasive method of examination may elucidate whether significant nerve exists and may also serve to pinpoint the location of injury. Such information allows the surgeon to more effectively and efficiently surgically expose the zone of injury and understand the boundaries of the nerve outside the zone of injury. Moreover, such preoperative evaluation may at times obviate the need for exploratory surgery at all. It is important for the anesthesiologist and surgeon to work together with respect to the ability to both interpret the ultrasound images and to clinically correlate the findings. The zone of tissue disruption in ballistic injuries is extremely variable. It is beneficial to both the surgeon and patient to engage in a collaborative effort with an experienced regional anesthesiologist who is well-versed in interpretation of ultrasound images and tissue plane disruption in an effort to minimize surgical time and the potential unintended consequences of unnecessary
All types of regenerative materials, including metal implants, porous scaffolds and cell-laden hydrogels, interact with the living tissue and cells. Such interaction is key to the settlement and regenerative outcomes of the biomaterials. Notably, the immune reactions from the host body crucially mediate the tissue-biomaterials interactions. Macrophages (as well as monocytes and neutrophils), traditionally best known as defenders, accumulate at the tissue-biomaterials interface and secrete abundant cytokines to create a microenvironment that benefits or inhibits regeneration. Because the phenotype of these cells is highly plastic in response to varying stimuli, it may be feasible to manipulate their activity at the interface and harness their power to mediate bone regeneration. Towards this goal, our team have been working on macrophage-driven bone regeneration in two aspects. First, targeting the abundant, glucan/mannan-recognising receptors on macrophages, we have devised a series of glucomannan polymers that can stimulate macrophages to secrete pro-osteogenic cytokines, and applied them as coating polymer of mesenchymal stem cells-laden hydrogels. Second, targeting the toll-like receptors (TLRs) on macrophages, we have screened TLR-activating polysaccharides and picked up zymosan (beta-glucan) to be modified onto titanium and glass implants. We evaluated both the efficacy of integration and safety of immune stimulation in both in vitro and in vivo models. Our future
Mesenchymal stem cells (MSC) have a well recognised potential for tissue repair. This potential is two pronged: they can differentiate into the functional cell types of the damaged tissues and they can support tissue recovery by secreting trophic factors, depositing an extracellular matrix (ECM) and dampening inflammation. Three-dimensional microscopy recently shown that MSCs in the bone marrow create an intricate proteo-cellular scaffold with the ECM forming an interconnected cellular continuum whose structure is guided by the deposited ECM. This proteo-cellular scaffold controls bone marrow functions from hematopoiesis to osteogenesis. In the current study we aimed to optimise ECM production under in vitro conditions by immortalised MSCs with the view that the generated ECM can be utilised for tissue repair. With immunocytochemistry we determined the deposition of bone marrow-characteristic ECM proteins: collagen I, III, IV, V, VI, laminin and fibronectin. While primary MSCs produced slightly higher amount ECM proteins than immortalised MSCs, the relative abundancy of the ECM proteins was very similar. In order to isolate the ECM, we optimised a decellularisation method based on gentle lysis with sodium-deoxycholate and DNase digestion. Immunostaining for collagen I, III, VI and fibronectin and labelling the nuclei with Hoechst-33342 confirmed removal of all cells while retaining the ECM in its original architecture. Ideally, the decellularised ECM retains associated cytokines and chemokines, such as CXCL12, important for attracting MSCs. To test this, we seeded Molm-13 leukemia cells on decellularised ECM as MSC-produced CXCL12- and other cytokines protect leukemia cells against chemotherapeutics. We found that the decellularisation process however removed these factors and thus for therapeutic purposes, the decellularised ECM would need to be re-loaded with the essential chemo/cytokines. Overall, we developed a system for decellularised ECM production by immortalised MSCs and the results warrant further
This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.Aims
Methods
Background. Multiple randomised controlled trials have demonstrated that arthroscopy provides little benefit in patients with knee osteoarthritis. In 2008, NICE released guidelines to reflect this evidence. Implementation has been sporadic, and arthroscopy for knee osteoarthritis is commonly performed with an annual incidence of 9.9 per 10,000 in England. Our aim was to establish whether previous arthroscopy affects Patient Reported Outcome Measures (PROMs) in Total Knee Replacement (TKR) patients. Methods. Data was retrospectively collected from 2010–2012 from a University hospital. Pre-operative and one-year post-operative PROMs were collected on patients who had undergone arthroscopy and then TKR, or only TKR. The change in PROMs score over TKR was then compared between groups. Results. Complete data was available for 85 patients: 36 had arthroscopy prior to TKR, with 49 receiving only TKR. There was no difference between the groups with regard to age and gender. Oxford Knee Score (OKS) before TKR for both groups were similar (arthroscopy group 41.9, non-arthroscopy 40.8). At arthroscopy 81% of patients had grade IV arthritis, with 19% demonstrating grade III. Patients who had arthroscopy before TKR had a worse response to TKR compared to those who did not have an arthroscopy (respective mean change of 23.79%, 38.4%, p< 0.001). Conclusions. Although this exploratory study is small and subject to selection bias, our data suggest that arthroscopy may have a detrimental effect on patient function after TKR. This may be due to psychological factors, as there is growing evidence to suggest stress and anxiety negatively affect PROMs4. Medicalisation of patients through arthroscopic procedures may contribute to poor PROMs. This study offers a potential pre-operative factor that may explain some of the variability in outcome seen with TKR. This relationship requires confirmation and
Background. The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option, however, its effectiveness in comparison to the two-stage strategy remains uncertain. A systematic review and meta-analysis was conducted to compare the effectiveness of one- and two-stage revision strategies to prevent re-infection after prosthetic hip infection. Methods. Cohort studies (prospective or retrospective) conducted in unselected patients with infection treated exclusively by one- or two-stage revision and reporting re-infection outcomes within two years of revision were retrieved from MEDLINE, EMBASE, Web of Science, Cochrane databases, manual search of bibliographies to March 2015, and email contact with investigators. Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics. Results. In 38 one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate for 60 two-stage studies was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no evidence of publication bias among contributing studies. Conclusion. Among unselected populations, evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision. More detailed analyses under a broader range of circumstances and
This case series highlights the use of the Ganz approach and surgical dislocation for excision of fibrous dysplasia of the femoral neck, pigmented villonodular synovitis and synovial chrondromatosis of the hip, which has never been described for use with all three tumours together. These are rare benign tumours, which were found incidentally and required excision. We demonstrate that it is possible to obtain excellent exposure of the femoral neck, head and acetabulum allowing easy inspection,
Demographics changes and the increasing incidence of metastatic bone disease are driving the significant issues of vertebral body (VB) fractures as an important consideration in the quality of life of the elderly. Whilst osteoporotic vertebral fractures have been widely studies both clinically and biomechanically, those fractures arising from metastatic infiltration in the spine are relatively poorly understood. Biomechanical in-vitro assessment of these structurally weaker specimens is an important methodology for gaining an understanding of the mechanics of such fractures in which a key aspect is the development of methodologies for predicting the failure load. Here we report on a method to predict the vertebral strength by combining computed tomography assessment with an engineering beam theory as an alternative to more complex finite element analyses and its verification within a laboratory scenario. Ninety-two human vertebral bodies with 3 different pathologies: osteoporosis, multiple myeloma (MM) and specimens containing cancer metastases were loaded using a define protocol and the failure loads recorded. Analysis of the resulting data demonstrated that the mean difference between predicted and experimental failure loads was 0.25kN, 0.41kN and 0.79 kN, with adjunct correlation coefficients of 0.93, 0.64 and 0.79 for osteoporotic, metastatic and MM VBs, respectively. Issues in predicting vertebral fracture arise from extra-vertebral bony formations which add to vertebral strength in osteoporotic VB but are structurally incompetent in metastatic disease. The methodology is currently used in providing better experimental design/benchmarking within in-vitro investigations together with further
Current knowledge regarding upper limb myotomes is based on historic papers. Recent advances in magnetic resonance imaging (MRI) and surgical
Purpose of study. To explore the clinical reasoning strategies used by extended scope physiotherapists (ESPs) when assessing patients with low back pain. Background. Extended scope physiotherapists commonly work in back pain services and their training emphasises the acquisition of clinical skills and possible diagnostic tests (including MRI) to aid clinical reasoning and diagnosis. Whilst there has been some