Aims. Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease. Methods. A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed. Results. A total of 161 studies were included, which covered capsule, ligaments, meniscus, skeletal muscle, synovium, and tendon in both humans and animals, and fat pad and intervertebral disc in humans only. These studies covered a wide variety of ECM features, including individual ECM components (i.e. collagens, proteoglycans, and glycoproteins), ECM architecture (i.e.
Aims. Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods. High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results. More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of
Damage to and repair of the acetabular labral-chondral complex are areas of clinical interest in the treatment of young adults with pain in the hip and in the prevention of degenerative arthritis of the hip. There are varying theories as to why most acetabular tears are located anterosuperiorly. We have studied the prenatal development of the human acetabular labral-chondral complex in 11 fetal hips, aged from eight weeks of gestation to term. There were consistent differences between the anterior and posterior acetabular labral-chondral complex throughout all ages of gestation. The anterior labrum had a somewhat marginal attachment to the acetabular cartilage with an intra-articular projection. The posterior labrum was attached and continuous with the acetabular cartilage. Anteriorly, the labral-chondral transition zone was sharp and abrupt, but posteriorly it was gradual and interdigitated. The
1. The surface of mature adult human articular cartilage from the knee has been studied by electron microscopy in eleven patients ranging in age from thirty-seven to eighty-three years. The ultrastructural appearance varies from person to person and often from area to area in the same specimen. These variations range from an intact surface to one showing overt fibrillation visible with the light microscope. 2. In areas where the articular surface appears intact the underlying superficial matrix consists of closely packed
Aims. Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology. Methods. In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry. Results. On MMP arrays, most of the targeted MMPs and TIMPs were detected in the FAI and normal labral proteins. After data normalization, in comparison with the normal labral proteins, expression of MMP-1 and MMP-2 in the FAI group was increased and expression of TIMP-1 reduced. The histology of the FAI labrum showed disorderly cell distribution and altered composition of thick and thin
Objectives. Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. Methods. A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). Results. Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented
Objectives. This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing. Materials and Methods. A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation. Results. While the SHG light intensity of the healing tendon samples was significantly lower than that of the uninjured tendon samples, 2D Fourier transform SHG images showed a clear difference in
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. Methods. A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization). Results. The pSFT remodelled into a ligament-like structure and no adverse inflammatory reaction was seen. The ground reaction force in the operated leg of the Endobutton group was higher at 11 weeks (p < 0.05). An indirect insertion was seen at the graft-bone interface characterized by Sharpey-like fibres. Qualitative differences in tendon remodelling were seen between the two groups, with greater crimp-like organization and more aligned
We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure. Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating
Objectives. After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP). Methods. Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing. Results. Histological analysis showed well organised arrangement of
We used an in vivo model to assess the use of an autogenous cancellous bone block and marrow graft for augmenting tendon reattachment to metallic implants. We hypothesised that augmentation of the tendon-implant interface with a bone block would enable retention of the graft on the implant surface, enhance biological integration, and result in more consistent functional outcomes compared with previously reported morcellised graft augmentation techniques. A significant improvement in functional weight-bearing was observed between six and 12 weeks. The significant increase in ground reaction force through the operated limb between six and 12 weeks was greater than that reported previously with morcellised graft augmented reconstructions. Histological appearance and
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
Bone samples from the iliac crest of patients with no signs of bone disorder were treated with collagenase to remove the collagen component and so allow detailed observation of the mineral hydroxyapatite. Both polished and unpolished surfaces were studied in the scanning electron microscope and they showed that the mineral component of bone is composed of small rounded units about 10 nm across which are fused together to form larger spheroidal units roughly 100 nm in diameter. In the unpolished surfaces these 100 nm units are seen to aggregate to form columns approximately parallel to their neighbours and with numerous interconnections forming a continuous mineral phase. The polished sections also show the hydroxyapatite as a continuous phase of contiguous spheroids and the holes from which the
While the evolution of the bony skeleton of the shoulder girdle is well described, there is little information regarding the soft tissues, in particular of the rotator cuff. We dissected the shoulders of 23 different species and compared the anatomical features of the tendons of the rotator cuff. The alignment and orientation of the
1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient. 2. The disease is characterised by a defect in the formation of the
1. A description is given of the pathology of a generalised skeletal disease characterised by a defect in the formation of the
We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an in vivo ovine model of reconstruction of the extensor mechanism at the knee. We hypothesised that augmentation of the tendon-implant interface with DBM would enhance the functional and histological outcomes as compared with previously reported control reconstructions without DBM. Function was assessed at six and 12 weeks postoperatively, and histological examination was undertaken at 12 weeks. A significant increase of 23.5% was observed in functional weight-bearing at six weeks in the DBM-augmented group compared with non-augmented controls (p = 0.004). By 12 weeks augmentation with DBM resulted in regeneration of a more direct-type enthesis, with regions of fibrocartilage, mineralised fibrocartilage and bone. In the controls the interface was predominantly indirect, with the tendon attached to the bone graft-hydroxyapatite base plate by perforating
Surgical treatment for traumatic, anterior glenohumeral instability requires repair of the anterior band of the inferior glenohumeral ligament, usually at the site of glenoid insertion, often combined with capsuloligamentous plication. In this study, we determined the mechanical properties of this ligament and the precise anatomy of its insertion into the glenoid in fresh-frozen glenohumeral joints of cadavers. Strength was measured by tensile testing of the glenoid-soft-tissue-humerus (G-ST-H) complex. Two other specimens of the complex were frozen in the position of apprehension, serially sectioned perpendicular to the plane containing the anterior and posterior rims of the glenoid, and stained with Toluidine Blue. On tensile testing, eight G-ST-H complexes failed at the site of the glenoid insertion, representing a Bankart lesion, two at the insertion into the humerus, and two at the midsubstance. For those which failed at the glenoid attachment the mean yield load was 491.0 N and the mean ultimate load, 585.0 N. At the glenoid region, stress at yield was 7.8 ± 1.3 MPa and stress at failure, 9.2 ± 1.5 MPa. The permanent deformation, defined as the difference between yield and ultimate deformation, was only 2.3 ± 0.8 mm. The strain at yield was 13.0 ± 0.7% and at failure, 15.4 ± 1.2%; therefore permanent strain was only 2.4 ± 1.1%. Histological examination showed that there were two attachments of the anterior band of the inferior glenohumeral ligament at the site of the glenoid insertion. In one, poorly organised
The experiments were performed to answer three main questions. These and our answers may be summarised as follows. What is the precise mechanism of healing of a raw bony surface in a joint? What cells are involved? Where do they originate?âIn all the implant experiments and in the control series the fundamental mechanism of healing was similar. 1. A massive proliferation of fibroblasts occurred from the cut periosteum, from the cut joint capsule, and to a lesser extent from the medullary canal. 2. Fibroblasts grew centripetally in the first few weeks after operation, attempting to form a "fibroblast cap" to the cut bone end. 3. Fibroblasts of this cap near the cut bone spicules metamorphosed to become prechondroblasts, chondroblasts laying down cartilage matrix, and hypertrophied (alkaline phosphatase-secreting) chondrocytes lying in a calcified matrix. 4. This calcified cartilage matrix was invaded by dilated capillaries probably bearing osteoblasts which laid down perivascular (endochondral) bone. 5. Some of the cells of projecting bone spicules died and their matrix was eroded in the presence of many osteoclasts. 6. In the control experiments of simple excision of the radial head new bone was produced at the periphery only by processes (3) and (4). This sealed off the underlying peripheral cortical bone from the superficially placed peripheral articular surface of fibrocartilage. At about a year from operation the central portion of the articular surface was still formed of bare bone, or of bone spicules covered by a thin layer of irregularly arranged
1. The orientation of
By polarising microscope and x-ray crystallographic techniques the annulus fibrosus has been shown to consist of regularly oriented sheets of
The surface ultrastructure of ganglia has been studied using the scanning electron microscope. This study showed that the ganglion wall consists of multidirectional strata of
1. All articulating cartilages are fibrocartilages. 2. The articular cartilages of the synovial joints are largely composed of
Thirty cruciate ligaments were retrieved from either cadavers or limbs which had been amputated. Each specimen was sectioned and stained to demonstrate the presence of collagen, nerves and vessels. All 30 specimens contained an interconnecting band of
The soft tissue response to carbon fibre was studied histologically one and a half years after being used to reconstruct the lateral collateral ligament of the human knee. A remarkably consistent pattern was seen in the induced ligament. The basic pattern was a "composite unit", consisting of a core of carbon fibre enveloped in a concentric manner by coherent layers of fibroblasts and
1. The arrangement of
1. Human articular cartilage from normal femoral heads and from cases of osteoarthrosis in subjects of various ages has been examined histologically and by electron microscopy. 2. In specimens from middle-aged and old subjects, peculiar "matrix-streaks" have been observed in the deep zone of the pressure areas as oblique bands extending from the pericellubar halos into the adjacent matrix. 3. Ultrastructurally the streaks are correlated with an undulating pattern of the radially oriented
We describe the histology of a specimen taken from an amputated leg seven months after a 15 cm bone gap in the tibia had been closed by bone transport. Lengthening appeared to have occurred by repeated minor trauma to the bone, with the fractured trabeculae in sufficiently close contact for the repair process to proceed. Osteogenesis did not occur through a cartilage phase, but the fracture gaps were bridged by
In a study combining tissue mechanics and fracture morphology for the first time, we examined the ruptured surfaces of anterior cruciate ligaments of rabbits and related their appearance to the initial loading conditions. Sixteen specimens were stretched to failure at rates of displacement of 10 and 500 mm/min. We used video images to study the changes which occurred during the fracture process and SEM to examine the appearance of the ruptured surfaces. The surfaces of ligaments tested at 10 mm/min had more pulled-out
We studied 16 club feet and 27 normal feet from spontaneously aborted human fetuses in the second trimester of gestation and measured the length of the spring ligament, and the declination angle and size of the talus. We also studied the cellular characteristics of the spring ligament and the immunohistochemical features of the medial ankle ligaments using monoclonal antibodies against type-III collagen, desmin, vimentin, and smooth muscle actin. Histomorphometric results indicated that the talar deformity was not the primary lesion. Histological and immunohistochemical findings showed that the cells and
1. When cortisone is administered to rabbits there is early rapid resorption of bone and a partial inhibition of new bone formation. After a few days the effect becomes less obvious, so that, if observations are made at later stages, the results may be ascribed then to simple inhibition of bone growth. 2. The effect of mechanical stress has been studied in the jaw. When tooth movement is induced mechanically there is, in ordinary circumstances, a resorption of bone on the side to which the tooth is moving (the "pressure" side) and bone formation on the opposite side (the "tension" side). After administration of cortisone there is increased resorption on the "pressure" side and there is greater resorption of connective tissues here. On the "tension" side there is resorption and inhibition of bone formation. 3. In the areas of stress, when cortisone is administered,
1. In the experiments undertaken autogenous vesical mucosal transplants were made in guinea-pigs. The transplanted mucosa proliferates and forms a nodule. Central necrosis of the nodule and the secretion of the proliferating epithelium combine to form a cyst filled with a viscous fluid. 2. Before the cyst is well defined some of this fluid diffuses into the sub-epithelial connective tissue, producing areas of tissue oedema which later are transformed into translucent hyaloid islands. With further condensation of the
Our aim was to examine the potential of autologous perichondral tissue to form a meniscal replacement. In 18 mature sheep we performed a complete medial meniscectomy. The animals were then divided into two groups: 12 had a meniscal replacement using strips of autologous perichondral tissue explanted from the lower rib (group G) and six (group C) served as a control group without a meniscal replacement. In all animals restriction from weight-bearing was achieved by means of transection and partial resection of tendo Achillis. Six animals (four from group G and two from group C) were each killed at 3, 6 and 12 months. The grafts and the underlying articular cartilage were removed and studied by gross macroscopic examination, light microscopy, SEM, polarised light examination, and by biomechanical tests. In all the transplanted animals a new perichondral meniscus developed. After three months the transplants resembled normal menisci in size and thickness, while in the control animals only small rims of spontaneously grown tissue were seen. Microscopically, the perichondral menisci showed a normal orientation of
Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments.Aims
Methods
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. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.Aims
Methods
A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed.Aims
Methods
Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.Aims
Methods
This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.Aims
Methods
Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors. Cite this article:
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. 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.Aims
Methods
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
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. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.Aims
Methods
Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.Aims
Methods
The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.Aims
Methods
The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects. HAAM scaffolds were constructed via trypsinization from fresh human amniotic membrane (HAM). The characteristics of the HAAM scaffolds were evaluated by haematoxylin and eosin (H&E) staining, picrosirius red staining, type II collagen immunostaining, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Human amniotic mesenchymal stem cells (hAMSCs) were isolated, and stemness was verified by multilineage differentiation. Then, third-generation (P3) hAMSCs were seeded on the HAAM scaffolds, and phalloidin staining and SEM were used to detect the growth of hAMSCs on the HAAM scaffolds. Osteochondral defects (diameter: 3.5 mm; depth: 3 mm) were created in the right patellar grooves of 20 New Zealand White rabbits. The rabbits were randomly divided into four groups: the control group (n = 5), the HAAM scaffolds group (n = 5), the JCFs group (n = 5), and the HAAM + JCFs group (n = 5). Macroscopic and histological assessments of the regenerated tissue were evaluated to validate the treatment results at 12 weeks.Aims
Methods
Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery. Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites.Aims
Methods
The October 2023 Foot & Ankle Roundup360 looks at: Risk factors for failure of total ankle arthroplasties; Effects of synovial fluid fracture haematoma to tissue-engineered cartilage; Coronal plane deformity in CMT-cavovarus feet using automated 3D measurements; Immediate weightbearing after ankle fracture fixation – is it safe?; Unlocking the mystery of Mueller-Weiss disease; Diabetic foot management: predictors of failure.
Injury to the triangular fibrocartilage complex (TFCC) may result in ulnar wrist pain with or without instability. One component of the TFCC, the radioulnar ligaments, serve as the primary soft-tissue stabilizer of the distal radioulnar joint (DRUJ). Tears or avulsions of its proximal, foveal attachment are thought to be associated with instability of the DRUJ, most noticed during loaded pronosupination. In the absence of detectable instability, injury of the foveal insertion of the radioulnar ligaments may be overlooked. While advanced imaging techniques such as MRI and radiocarpal arthroscopy are well-suited for diagnosing central and distal TFCC tears, partial and complete foveal tears without instability may be missed without a high degree of suspicion. While technically challenging, DRUJ arthroscopy provides the most accurate method of detecting foveal abnormalities. In this annotation the spectrum of foveal injuries is discussed and a modified classification scheme is proposed. Cite this article:
Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model. We exposed zebrafish to 3 g and 6 g hypergravity from three to five days post-fertilization, when key events in jaw cartilage morphogenesis occur. Following this exposure, we performed immunostaining along with a range of histological stains and transmission electron microscopy (TEM) to examine cartilage morphology and structure, atomic force microscopy (AFM) and nanoindentation experiments to investigate the cartilage material properties, and finite element modelling to map the pattern of strain and stress in the skeletal rudiments.Aims
Methods
We investigated the prevalence of late developmental dysplasia of the hip (DDH), abduction bracing treatment, and surgical procedures performed following the implementation of universal ultrasound screening versus selective ultrasound screening programmes. A systematic search of PubMed, Embase, The Cochrane Library, OrthoSearch, and Web of Science from the date of inception of each database until 27 March 2022 was performed. The primary outcome of interest was the prevalence of late detection of DDH, diagnosed after three months. Secondary outcomes of interest were the prevalence of abduction bracing treatment and surgical procedures performed in childhood for dysplasia. Only studies describing the primary outcome of interest were included.Aims
Methods
Dupuytren’s contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis. We compared the expression of the adipocytokines adiponectin and leptin in the adipose tissue surrounding the palmar aponeurosis of male patients with Dupuytren’s contracture, and of male patients with carpal tunnel syndrome (CTS) as the control group. We also examined the effects of adiponectin on fibrosis-related genes and proteins expressed by fibroblasts in the palmar aponeurosis of patients with Dupuytren’s contracture.Aims
Methods
The December 2022 Shoulder & Elbow Roundup360 looks at: Biceps tenotomy versus soft-tissue tenodesis in females aged 60 years and older with rotator cuff tears; Resistance training combined with corticosteroid injections or tendon needling in patients with lateral elbow tendinopathy; Two-year functional outcomes of completely displaced midshaft clavicle fractures in adolescents; Patients who undergo rotator cuff repair can safely return to driving at two weeks postoperatively; Are two plates better than one? A systematic review of dual plating for acute midshaft clavicle fractures; Treatment of acute distal biceps tendon ruptures; Rotator cuff tendinopathy: disability associated with depression rather than pathology severity; Coonrad-Morrey total elbow arthroplasty implications in young patients with post-traumatic sequelae.
Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model. A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.Aims
Methods
After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed.Aims
Methods
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.
The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (Aims
Methods
Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article:
Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model. A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks.Aims
Methods
Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold. Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.Aims
Methods
This study aims to evaluate a new home medical stretching device called the Self Treatment Assisted Knee (STAK) tool to treat knee arthrofibrosis. 35 patients post-major knee surgery with arthrofibrosis and mean range of movement (ROM) of 68° were recruited. Both the STAK intervention and control group received standard physiotherapy for eight weeks, with the intervention group additionally using the STAK at home. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Scores (OKS) were collected at all timepoints. An acceptability and home exercise questionnaire capturing adherence was recorded after each of the interventions.Aims
Methods
Here we introduce a wide and complex study comparing effects of growth factors used alone and in combinations on human mesenchymal stem cell (hMSC) proliferation and osteogenic differentiation. Certain ways of cell behaviour can be triggered by specific peptides – growth factors, influencing cell fate through surface cellular receptors. In our study transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) were used in order to induce osteogenesis and proliferation of hMSCs from bone marrow. These cells are naturally able to differentiate into various mesodermal cell lines. Effect of each factor itself is pretty well known. We designed experimental groups where two and more growth factors were combined. We supposed cumulative effect would appear when more growth factors with the same effect were combined. The cellular metabolism was evaluated using MTS assay and double-stranded DNA (dsDNA) amount using PicoGreen assay. Alkaline phosphatase (ALP) activity, as early osteogenesis marker, was observed. Phase contrast microscopy was used for cell morphology evaluation.Aims
Methods
The purpose of this study was to compare clinical results, long-term survival, and complication rates of stemless shoulder prosthesis with stemmed anatomical shoulder prostheses for treatment of osteoarthritis and to analyze radiological bone changes around the implants during follow-up. A total of 161 patients treated with either a stemmed or a stemless shoulder arthroplasty for primary osteoarthritis of the shoulder were evaluated with a mean follow-up of 118 months (102 to 158). The Constant score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) score, and active range of motion (ROM) were recorded. Radiological analysis for bone adaptations was performed by plain radiographs. A Kaplan-Meier survivorship analysis was calculated and complications were noted.Aims
Methods
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. A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.Aims
Methods
The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1). A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13). Expression of related proteins was detected by Western blotting.Objectives
Methods
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. 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).Aims
Materials and Methods
Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote Within the present study, we evaluated whether this promising new method, using 99mTc-hydroxydiphosphonate (99mTc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with 99mTc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured.Objectives
Methods
As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article:
Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health. Cite this article:
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. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Aims
Methods
Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries. We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in animal models. The studies were screened for inclusion based on randomization, controls, and reported measurable outcomes. The RevMan software package was used for the meta-analysis.Objectives
Methods
The aim of this study was to investigate the biomechanical effect of the anterolateral ligament (ALL), anterior cruciate ligament (ACL), or both ALL and ACL on kinematics under dynamic loading conditions using dynamic simulation subject-specific knee models. Five subject-specific musculoskeletal models were validated with computationally predicted muscle activation, electromyography data, and previous experimental data to analyze effects of the ALL and ACL on knee kinematics under gait and squat loading conditions.Objectives
Methods
The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours Objectives
Methods
The acetabular labrum is a soft-tissue structure
which lines the acetabular rim of the hip joint. Its role in hip
joint biomechanics and joint health has been of particular interest
over the past decade. In normal hip joint biomechanics, the labrum
is crucial in retaining a layer of pressurised intra-articular fluid
for joint lubrication and load support/distribution. Its seal around
the femoral head is further regarded as a contributing to hip stability through
its suction effect. The labrum itself is also important in increasing
contact area thereby reducing contact stress. Given the labrum’s
role in normal hip joint biomechanics, surgical techniques for managing
labral damage are continuously evolving as our understanding of
its anatomy and function continue to progress. The current paper
aims to review the anatomy and biomechanical function of the labrum
and how they are affected by differing surgical techniques. Take home message: The acetabular labrum plays a critical role
in hip function and maintaining and restoring its function during
surgical intervention remain an essential goal. Cite this article:
The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight ‘middle-aged’ baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically. Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature. Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing.
The purpose of this study was to evaluate chronological changes
in the collagen-type composition at tendon–bone interface during
tendon–bone healing and to clarify the continuity between Sharpey-like
fibres and inner fibres of the tendon. Male white rabbits were used to create an extra-articular bone–tendon
graft model by grafting the extensor digitorum longus into a bone
tunnel. Three rabbits were killed at two, four, eight, 12 and 26
weeks post-operatively. Elastica van Gieson staining was used to colour
5 µm coronal sections, which were examined under optical and polarised
light microscopy. Immunostaining for type I, II and III collagen
was also performed.Objectives
Methods
We investigated the effect of mitomycin-C on the reduction of the formation of peritendinous fibrous adhesions after tendon repair. In 20 Wistar albino rats the tendo Achillis was cut and repaired using a modified Kessler technique. The rats were divided into two equal groups. In group 1, an injection of mitomycin-C was placed between the tendon and skin of the right leg. In group 2, an identical volume of sterile normal saline was injected on the left side in a similar fashion. All the rats received mitomycin-C or saline for four weeks starting from the day of operation. The animals were killed after 30 days. The formation of peritendinous fibrous tissue, the inflammatory reaction and tendon healing were evaluated. The tensile strength of the repaired tendons was measured biomechanically. Microscopic evidence of the formation of adhesions and inflammation was less in group 1. There was no significant difference in the tensile load required to rupture the repaired tendons in the two groups. Mitomycin-C may therefore provide a simple and inexpensive means of preventing of post-operative adhesions.
Treatment for osteoarthritis (OA) has traditionally
focused on joint replacement for end-stage disease. An increasing number
of surgical and pharmaceutical strategies for disease prevention
have now been proposed. However, these require the ability to identify
OA at a stage when it is potentially reversible, and detect small
changes in cartilage structure and function to enable treatment
efficacy to be evaluated within an acceptable timeframe. This has
not been possible using conventional imaging techniques but recent
advances in musculoskeletal imaging have been significant. In this
review we discuss the role of different imaging modalities in the
diagnosis of the earliest changes of OA. The increasing number of
MRI sequences that are able to non-invasively detect biochemical
changes in cartilage that precede structural damage may offer a
great advance in the diagnosis and treatment of this debilitating
condition. Cite this article:
We have used Fourier transform infrared spectroscopy (FTIR) to characterise the chemical and structural composition of the tendons of the rotator cuff and to identify structural differences among anatomically distinct tears. Such information may help to identify biomarkers of tears and to provide insight into the rates of healing of different sizes of tear. The infrared spectra of 81 partial, small, medium, large and massive tears were measured using FTIR and compared with 11 uninjured control tendons. All the spectra were classified using standard techniques of multivariate analysis. FTIR readily differentiates between normal and torn tendons, and different sizes of tear. We identified the key discriminating molecules and spectra altered in torn tendons to be carbohydrates/phospholipids (1030 cm−1 to 1200 cm−1), collagen (1300 cm−1 to 1700 cm−1 and 3000 cm−1 to 3350 cm−1) and lipids (2800 cm−1 to 3000 cm−1). Our study has shown that FTIR spectroscopy can identify tears of the rotator cuff of varying size based upon distinguishable chemical and structural features. The onset of a tear is mainly associated with altered structural arrangements of collagen, with changes in lipids and carbohydrates. The approach described is rapid and has the potential to be used peri-operatively to determine the quality of the tendon and the extent of the disease, thus guiding surgical repair.
The aim of this study was to examine whether asymmetric loading
influences macrophage elastase (MMP12) expression in different parts
of a rat tail intervertebral disc and growth plate and if MMP12
expression is correlated with the severity of the deformity. A wedge deformity between the ninth and tenth tail vertebrae
was produced with an Ilizarov-type mini external fixator in 45 female
Wistar rats, matched for their age and weight. Three groups were
created according to the degree of deformity (10°, 30° and 50°).
A total of 30 discs and vertebrae were evaluated immunohistochemically
for immunolocalisation of MMP12 expression, and 15 discs were analysed
by western blot and zymography in order to detect pro- and active
MMP12.Objectives
Methods
We developed an Kinematic gait analysis showed nearly normal function of the joint by 12 weeks. Force-plate assessment showed a significant increase in functional weight-bearing in the grafted animals (p = 0.043). The tendon-implant interface showed that without graft, encapsulation of fibrous tissue occurred. With autograft, a developing tendon-bone-HA-implant interface was observed at six weeks and by 12 weeks a layered tendon-fibrocartilage-bone interface was seen which was similar to a direct-type enthesis. With stable mechanical fixation, an appropriate bioactive surface and biological augmentation the development of a functional tendon-implant interface can be achieved.
In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained
To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. 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.Objectives
Methods
As one of the heat-stable enterotoxins, Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses.Objectives
Materials and Methods
Advances in hip arthroscopy have renewed interest in the ligamentum teres. Considered by many to be a developmental vestige, it is now recognised as a significant potential source of pain and mechanical symptoms arising from the hip joint. Despite improvements in imaging, arthroscopy remains the optimum method of diagnosing lesions of the ligamentum teres. Several biological or mechanical roles have been proposed for the ligament. Unless these are disproved, the use of surgical procedures that sacrifice the ligamentum teres, as in surgical dislocation of the hip, should be carefully considered. This paper provides an update on the development, structure and function of the ligamentum teres, and discusses associated clinical implications.
Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP.Objectives
Methods
Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge.
Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified. We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included.Objectives
Methods
Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.
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. 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.Objectives
Methods
Platelet-rich fibrin matrix (PRFM) has been proved to enhance tenocyte proliferation but has mixed results when used during rotator cuff repair. The optimal PRFM preparation protocol should be determined before clinical application. To screen the best PRFM to each individual’s tenocytes effectively, small-diameter culture wells should be used to increase variables. The gelling effect of PRFM will occur when small-diameter culture wells are used. A co-culture device should be designed to avoid this effect. Tenocytes harvested during rotator cuff repair and blood from a healthy volunteer were used. Tenocytes were seeded in 96-, 24-, 12-, and six-well plates and co-culture devices. Appropriate volumes of PRFM, according to the surface area of each culture well, were treated with tenocytes for seven days. The co-culture device was designed to avoid the gelling effect that occurred in the small-diameter culture well. Cell proliferation was analyzed by water soluble tetrazolium-1 (WST-1) bioassay.Objectives
Methods
Our aim was to describe the mid-term appearances of the repair
process of the Achilles tendon after tenotomy in children with a
clubfoot treated using the Ponseti method. A total of 15 children (ten boys, five girls) with idiopathic
clubfoot were evaluated at a mean of 6.8 years (5.4 to 8.1) after
complete percutaneous division of the Achilles tendon. The contour
and subjective thickness of the tendon were recorded, and superficial
defects and its strength were assessed clinically. The echogenicity,
texture, thickness, peritendinous irregularities and potential for
deformation of the tendon were evaluated by ultrasonography.Aims
Patients and Methods
We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks. The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022). The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.
The present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an Specifically, canine flexor digitorum profundus tendons were used for this study and were divided into the following groups: (1) untreated, unprocessed normal tendon; (2) decellularised tendon; (3) bone marrow stromal cell (BMSC)-seeded tendon; and (4) BMSC-seeded and cyclically stretched tendon. Lateral slits were introduced on the tendon to facilitate cell seeding. Tendons from all four study groups were distracted by a servohydraulic testing machine. Tensile force and displacement data were continuously recorded at a sample rate of 20 Hz until 200 Newton of force was reached. Before testing, the cross-sectional dimensions of each tendon were measured with a digital caliper. Young’s modulus was calculated from the slope of the linear region of the stress-strain curve. The BMSCs were labeled for histological and cell viability evaluation on the decellularized tendon scaffold under a confocal microscope. Gene expression levels of selected extracellular matrix tendon growth factor genes were measured. Results were reported as mean ± SD and data was analyzed with one-way ANOVAs followed by Tukey’s post hoc multiple-comparison test.Objectives
Methods
Anterior cruciate ligament (ACL) reconstruction
is commonly performed and has been for many years. Despite this, the
technical details related to ACL anatomy, such as tunnel placement,
are still a topic for debate. In this paper, we introduce the flat
ribbon concept of the anatomy of the ACL, and its relevance to clinical
practice. Cite this article:
The pathogenesis of rotator cuff disease (RCD) is complex and
not fully understood. This systematic review set out to summarise
the histological and molecular changes that occur throughout the
spectrum of RCD. We conducted a systematic review of the scientific literature
with specific inclusion and exclusion criteria.Introduction
Methods
In recent years, the plantaris tendon has been
implicated in the development of chronic painful mid-portion Achilles tendinopathy.
In some cases, a thickened plantaris tendon is closely associated
with the Achilles tendon, and surgical excision of the plantaris
tendon has been reported to be curative in patients who have not
derived benefit following conservative treatment and surgical interventions. The aim of this review is to outline the basic aspects of, and
the recent research findings, related to the plantaris tendon, covering
anatomical and clinical studies including those dealing with histology,
imaging and treatment. Cite this article
Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.
Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson’s ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.
