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Bone & Joint Research
Vol. 12, Issue 3 | Pages 219 - 230
10 Mar 2023
Wang L Li S Xiao H Zhang T Liu Y Hu J Xu D Lu H

Aims

It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth.

Methods

C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs.


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 931 - 938
1 May 2021
Liu Y Lu H Xu H Xie W Chen X Fu Z Zhang D Jiang B

Aims

The morphology of medial malleolar fracture is highly variable and difficult to characterize without 3D reconstruction. There is also no universally accepeted classification system. Thus, we aimed to characterize fracture patterns of the medial malleolus and propose a classification scheme based on 3D CT reconstruction.

Methods

We retrospectively reviewed 537 consecutive cases of ankle fractures involving the medial malleolus treated in our institution. 3D fracture maps were produced by superimposing all the fracture lines onto a standard template. We sliced fracture fragments and the standard template based on selected sagittal and coronal planes to create 2D fracture maps, where angles α and β were measured. Angles α and β were defined as the acute angles formed by the fracture line and the horizontal line on the selected planes.


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An established rabbit model was used to preliminarily investigate the effect of acellular triphase, namely bone-cartilage-tendon, scaffold (ATS) sandwiched with autologous bone mesenchymal stem cells (BMSCs) sheets on tendon-bone interface healing. Bone, fibrocartilage and tendon tissue were harvested from the rabbits and sectioned into a book-type scaffold. The scaffolds were decellularized and their characterization was presented. BMSCs were isolated and co-cultured with the scaffolds to verify their cytocompatibility. BMSCs sheets were fabricated and inserted into the book page of the scaffold to construct an autologous BMSCs-sheets/book-type ATS complex. The complex was implated in the right knee of rabbits which operated standard partial patellectomy for TBI regeneration using Imaging, histological and biomechanical examinations.

The bone, fibrocartilage and tendon tissue were sectioned into a book-type scaffold before decellularization. Then we decellularized the above tissue and mostly preserved their microstructure and composition of the natural extracellular matrix, including collagen and proteoglycan. After the physicochemical and biological properties of the book-type ATS were evaluated, autologous BMSCs sheets were inserted into the book page of the scaffold to construct an autologous BMSCs-sheets/book-type ATS implants for TBI regeneration. In addition, the ATS has the advantages of non-toxicity, suitable for cell adhesion and growth as well as low immunogenicity while co-cultured with the BMSCs. At the same time, different scaffolds has the ability to induce the osteogenic, chondrogenic and tenogenic differentiation of BMSCs by immunofluorescence, reverse transcription-polymerase chain reaction and western blot analysis.

To determine the efficacy of the tissue-engineered implants for TBI regeneration, we transplanted it into a rabbit patella-patellar tendon (PPT) injury model, and the rabbits were sacrificed at postoperative week 8 or 16 for the radiological, histological, and mechanical evaluation. Radiologically, Synchrotron radiation micro-computed tomography (SR-μCT) showed that BMSCs/ATS group significantly increased bone area, BV/TV, trabecular thickness and trabecular number at the healing interface as compared with other groups at postoperative week 8 or 16. Histologically, the BMSCs/ATS group showed more woven bone, and a more robust fibrocartilaginous junction with a characteristic matrix rich in proteoglycans was seen at the PPT healing interface in comparison with other groups after 8 weeks. At week 16, the healing interface in 3 groups displayed better remodeling with respect to postoperative week 8. Healing and remodeling at the PPT junction were almost complete, with a resemblance to a healthy BTI consisting of the characteristic 4 zones in all groups. At last, we used biomechanical test as functional parameters to evaluate the quality of tendon-bone healing. Biomechanical testing indicated that BMSCs/ATS group showed significantly higher failure load and stiffness than other groups at postoperative week 8 and 16.

The complex composed of acellular triphase, namely bone-cartilage-tendon, scaffold (ATS) sandwiched with autologous bone mesenchymal stem cells (BMSCs) sheets can simulate the gradient structure of tendon-bone interface, inducing stem cell directional differentiation, so as to promote patella-patellar tendon interface healing effectively after injury.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 25 - 25
1 Jan 2017
Shih K Lin C Lu H Lin C Lu T
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Total knee replacements (TKR) have been the main choice of treatment for alleviating pain and restoring physical function in advanced degenerative osteoarthritis of the knee. Recently, there has been a rising interest in minimally invasive surgery TKR (MIS-TKR). However, accurate restoration of the knee axis presents a great challenge. Patient-specific-instrumented TKR (PSI-TKR) was thus developed to address the issue. However, the efficacy of this new approach has yet to be determined. The purpose of the current study was thus to measure and compare the 3D kinematics of the MIS-TKR and PSI-TKR in vivo during sit-to-stand using a 3D fluoroscopy technology.

Five patients each with MIS-TKR and PSI-TKR participated in the current study with informed written consent. Each subject performed quiet standing to define their own neutral positions and then sit-to-stand while under the surveillance of a bi-planar fluoroscopy system (ALLURA XPER FD, Philips). For the determination of the 3D TKR kinematics, the computer-aided design (CAD) model of the TKR for each subject was obtained from the manufacturer including femoral and tibial components and the plastic insert. At each image frame, the CAD model was registered to the fluoroscopy image via a validated 2D-to-3D registration method. The CAD model of each prosthesis component was embedded with a coordinate system with the origin at the mid-point of the femoral epicondyles, the z-axis directed to the right, the y-axis directed superiorly, and the x-axis directed anteriorly. From the accurately registered poses of the femoral and tibial components, the angles of the TKR were obtained following a z-x-y cardanic rotation sequence, corresponding to flexion/extension, adduction/abduction and internal/external rotation.

During sit-to-stand the patterns and magnitudes of the translations were similar between the MIS-TKR and PSI-TKR groups, with posterior translations ranging from 10–20 mm and proximal translations from 29–31mm. Differences in mediolateral translations existed between the groups but the magnitudes were too small to be clinically significant. For angular kinematics, both groups showed close-to-zero abduction/adduction, but the PSI-TKR group rotated externally from an internally rotated position (10° of internal rotation) to the neutral position, while the MIS-TKR group maintained at an externally rotated position of less than 5° during the movement.

During sit-to-stand both groups showed similar patterns and magnitudes in the translations but significant differences in the angular kinematics existed between the groups. While the MIS-TKR group maintained at an externally rotated position during the movement, the PSI-TKR group showed external rotations during knee extension, a pattern similar to the screw home mechanism in a normal knee, which may be related to more accurate restoration of the knee axis in the PSI-TKR group. A close-to-normal angular motion may be beneficial for maintaining a normal articular contact pattern, which is helpful for the endurance of the TKR. The current study was the first attempt to quantify the kinematic differences between PSI and non-PSI MIS. Further studies to include more subjects will be needed to confirm the current findings. More detailed analysis of the contact patterns is also needed.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 222 - 222
1 Jul 2014
Lu H Hu J Cao Y Wu T Li D Cao M
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Summary Statement

In this study, we employed a novel imaging modalities, the synchrotron radiation microcomputed tomography (SRμCT) to visualise the 3D morphology of the spinal cord microvasculature and successfully obtained the 3D images.

Introduction

Understanding the morphology of the spinal cord microvasculature in three-dimensions (3D) is limited by the lack of an effective high-resolution imaging technique. In this study, we used two novel imaging modalities, conventional x-ray microcomputed tomography (CμCT) and synchrotron radiation microcomputed tomography (SRμCT), to visualise the 3D morphology of the spinal cord microvasculature and to compare their utility in basic science research.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 20 - 20
1 Jul 2014
Lu H Hu J Zhou J Zeng Z Cao Y Chen C
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Summary Statement

We successfully delineated the 3D micro morphology of chondrocytes in patella-patellar tendon using IL-XPCT for the first time. Compared with conventional histology, IL-XPCT can not only provide a higher resolution imgaing but also keep the 3D integrity of the specimen.

Introduction

The morphology of the bone-tendon junction was complex and quite different from other organs, which result the injured bone-tendon junction repair process too slowly. To study the micro morphology of the bone-tendon junction in 3D may have a great significant value to revealing the repair mechanisms of this pathological process and accelerating injured bone-tendon junction repair. However, it was hindered by the convention methods such as histologic section. In our study, a novel imaging tool, synchrotron radiation based in-line x-ray phase contrast imaging (IL-XPCT) was used to research the 3D micro morphology of the bone-tendon junction.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 231 - 231
1 Jul 2014
Lu H Kuo C Lin C Lu T
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Summary Statement

The current study introduced the effects of projection errors on ankle morphological measurements using CT-based simulated radiographs by correlation analysis between 2D/3D dimensions and reliability analysis with randomised perturbations while measuring planar parameters on radiographs.

Introduction

Clinical success of total ankle arthroplasty (TAA) depends heavily on the available anatomy-based information of the morphology for using implants of precisely matched sizes. Among the clinically available medical imaging modalities, bi-planar projective radiographs are commonly used for this purpose owing to their convenience, low cost, and low radiation dose compared with other modalities such as MRI or CT. However, the intrinsic articular surface of the ankle joint is not symmetrical and oblique which implies that it is difficult to describe all the anatomical dimensions in detail with only one radiograph, thereby hindering the determination of accurate ankle morphometric parameters. The purposes of this study were to compare the measurements of ankle morphology using 3D CT images with those on planar 2D images; and to quantify the repeatability of the 2D measurements under simulated random perturbations.


Major orthopaedic surgeries such as total hip and total knee replacements are considered a major risk factor for venous thromboembolism (VTE). Without prophylaxis, DVT occurs in 10–40% of general surgical or medical patients and 40–60% of patients following major orthopaedic surgery. There has, however, been a perception that VTE is less common in Asia than in Western countries. New evidence has emerged recently that contradicts this perception. Results from multinational epidemiological studies (SMART, AIDA, ENDORSE) clearly showed that the rate of venographic and symptomatic thrombosis after major joint replacement in Asian patients is similar to that previously reported in patients in Western countries. However, thromboprophylaxis is not routinely used in Asia, even in situations considered high risk in Western countries. The ENDORSE study reported that less than 20% of at-risk surgical patients in Asia received prophylaxis compared with over 80% in Western countries. This leaves the majority of patients at risk of developing VTE and VTE-related conditions, which continues after hospital discharge. Current guidelines recommend the use of thromboprophylaxis for at least 10 days and up to 35 days in patients undergoing total joint replacement. Available anticoagulants are effective at preventing VTE but are associated with various limitations, such as parenteral administration as in the case of UFH and LMWH. A narrow therapeutic window, unpredictable pharmacology, frequent coagulation monitoring and dose-adjustment as in the case of vitamin K antagonists (VKAs). Several new, oral anticoagulants are in advanced clinical development, including the direct thrombin inhibitor, dabigatran, and the direct Factor Xa inhibitors, rivaroxaban and apixaban.