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Stem Cell Research & Therapy Jun 2024In the realm of studying joint-related diseases, there is a continuous quest for more accurate and representative models. Recently, regenerative medicine and tissue... (Review)
Review
In the realm of studying joint-related diseases, there is a continuous quest for more accurate and representative models. Recently, regenerative medicine and tissue engineering have seen a growing interest in utilizing organoids as powerful tools for studying complex biological systems in vitro. Organoids, three-dimensional structures replicating the architecture and function of organs, provide a unique platform for investigating disease mechanisms, drug responses, and tissue regeneration. The surge in organoid research is fueled by the need for physiologically relevant models to bridge the gap between traditional cell cultures and in vivo studies. Osteochondral organoids have emerged as a promising avenue in this pursuit, offering a better platform to mimic the intricate biological interactions within bone and cartilage. This review explores the significance of osteochondral organoids and the need for their development in advancing our understanding and treatment of bone and cartilage-related diseases. It summarizes osteochondral organoids' insights and research progress, focusing on their composition, materials, cell sources, and cultivation methods, as well as the concept of organoids on chips and application scenarios. Additionally, we address the limitations and challenges these organoids face, emphasizing the necessity for further research to overcome these obstacles and facilitate orthopedic regeneration.
Topics: Organoids; Humans; Tissue Engineering; Animals; Cartilage; Regenerative Medicine; Bone and Bones
PubMed: 38902814
DOI: 10.1186/s13287-024-03790-5 -
Annals of Biomedical Engineering Jun 2024In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of...
In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of mid-infrared (MIR) spectroscopy for detecting structural, compositional, and functional changes in AC resulting from two injury types. Three grooves (two in parallel in the palmar-dorsal direction and one in the mediolateral direction) were made via arthrotomy in the AC of the radial facet of the third carpal bone (middle carpal joint) and of the intermediate carpal bone (the radiocarpal joint) of nine healthy adult female Shetland ponies (age = 6.8 ± 2.6 years; range 4-13 years) using blunt and sharp tools. The defects were randomly assigned to each of the two joints. Ponies underwent a 3-week box rest followed by 8 weeks of treadmill training and 26 weeks of free pasture exercise before being euthanized for osteochondral sample collection. The osteochondral samples underwent biomechanical indentation testing, followed by MIR spectroscopic assessment. Digital densitometry was conducted afterward to estimate the tissue's proteoglycan (PG) content. Subsequently, machine learning models were developed to classify the samples to estimate their biomechanical properties and PG content based on the MIR spectra according to injury type. Results show that MIR is able to discriminate healthy from injured AC (91%) and between injury types (88%). The method can also estimate AC properties with relatively low error (thickness = 12.7% mm, equilibrium modulus = 10.7% MPa, instantaneous modulus = 11.8% MPa). These findings demonstrate the potential of MIR spectroscopy as a tool for assessment of AC integrity changes that result from injury.
PubMed: 38902468
DOI: 10.1007/s10439-024-03540-x -
Clinical Orthopaedics and Related... Jun 2024Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that...
BACKGROUND
Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated.
QUESTIONS/PURPOSES
(1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin?
METHODS
Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS.
RESULTS
Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01).
CONCLUSION
A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors.
LEVEL OF EVIDENCE
Level III, diagnostic study.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Magnetic Resonance Imaging; Adult; Bone Neoplasms; Chondrosarcoma; Biopsy; Aged; Pelvic Bones; Predictive Value of Tests; Risk Assessment; Young Adult; Risk Factors; Margins of Excision; Adolescent; Preoperative Care; Disease-Free Survival
PubMed: 38901841
DOI: 10.1097/CORR.0000000000003065 -
Cartilage Mar 2024A novel aragonite-based scaffold has been developed. In this study, mid-term clinical and magnetic resonance imaging (MRI) results on 12 patients affected by isolated...
OBJECTIVE
A novel aragonite-based scaffold has been developed. In this study, mid-term clinical and magnetic resonance imaging (MRI) results on 12 patients affected by isolated chondral or osteochondral lesions of the knee treated by the scaffold implantation have been evaluated at a mean follow-up of 6.5 (range: 5-8) years.
DESIGN
The study population consisted of 3 females and 9 males, mean age 34.4 (20-51) years. The lesion was located on the medial femoral condyle, the trochlea, and the lateral femoral condyle in 5, 5, and 2 patients, respectively. In all cases, a single lesion over grade 3 of the International Cartilage Restoration and Joint Preservation Society (ICRS) classification was treated: in 9 cases by implantation of one plug, and in 2 cases with 2 plugs; the mean size of the lesion was 2.5 cm (1-7).
RESULTS
One patient failed and was revised with a custom-made metal implant (Episealer). Overall, Knee Injury and Osteoarthritis Outcome Score (KOOS) significantly improved from 45 ± 13 preoperatively to 86 ± 13 at final follow-up. All KOOS subscales improved significantly: pain subscale increased from 48 ± 12 to 92 ± 11; symptoms from 66 ± 13 to 91 ± 13; activity of daily living (ADL) from 60 ± 19 to 90 ± 21; sport from 23 ± 20 to 75 ± 20; finally, quality of life (QoL) increased from 27 ± 14 to 77 ± 19. Long-term MRI MOCART score was 64.
CONCLUSIONS
This study shows continued significant clinical improvement and good magnetic resonance imaging (MRI) findings with a minimum 5 years follow-up after implantation of a novel aragonite derived scaffold for the treatment of cartilage lesions of the knee. One patient failed and was revised with a custom-made metal implant (Episealer).
PubMed: 38899593
DOI: 10.1177/19476035241227346 -
European Journal of Radiology Jun 2024The trapeziometacarpal (TMC) joint is a complex joint, whose anatomy and function are different from the metacarpophalangeal joints of the long fingers. The stability of... (Review)
Review
INTRODUCTION
The trapeziometacarpal (TMC) joint is a complex joint, whose anatomy and function are different from the metacarpophalangeal joints of the long fingers. The stability of this joint is ensured at three levels by multiple structures: osteochondral, capsulo-ligamentous, and musculo-tendinous. The anatomical and biomechanical structures ensuring the stability of the TMC joint are perfectly evaluated on magnetic resonance imaging (MRI), with a high degree of confidence. All described ligaments are anatomically visible and perfectly assessed on MRI and ultrasound (US): the dorsoradial ligament, the posterior oblique ligament, the intermetacarpal ligament, the ulnar collateral ligament, the two bundles of the anterior oblique ligament (break ligament), as well as the superficial anterior oblique and deep anterior oblique ligaments.
METHODOLOGY
This educational review assesses the TMC joint anatomy using high-field MRI and US compared with cadaveric specimens as well the biomechanics of this joint. In addition, it highlights pathological patterns of traumatic (sprain, dislocation, and fractures) and degenerative diseases.
RESULTS AND CONCLUSION
Knowledge of TMC joint anatomy is crucial to the radiologists' understanding and assessment of various traumatic and degenerative pathologies, and thus helps clinicians and surgeons choose the appropriate treatment.
PubMed: 38897054
DOI: 10.1016/j.ejrad.2024.111561 -
Cells Jun 2024Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory... (Review)
Review
Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 , 149 , 470 , and 74 were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.
Topics: Animals; Temporomandibular Joint; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Temporomandibular Joint Disorders; Humans; Osteoarthritis; Extracellular Vesicles; Disease Models, Animal
PubMed: 38891122
DOI: 10.3390/cells13110990 -
Cartilage Jun 2024Multilineage differentiating stress-enduring (Muse) cells, a pluripotent stem cell subset of mesenchymal stem cells (MSCs), have shown promise for various tissue repairs...
OBJECTIVE
Multilineage differentiating stress-enduring (Muse) cells, a pluripotent stem cell subset of mesenchymal stem cells (MSCs), have shown promise for various tissue repairs due to their stress tolerance and multipotent capabilities. We aimed to investigate the differentiation potential , the dynamics , and the reparative contribution of Muse cells to osteochondral lesions.
DESIGN
Labeled MSCs were cultured and sorted into Muse and non-Muse (MSCs without Muse cells) groups. These cells were then formed into spheroids, and chondrogenic differentiation was assessed . Twenty-one immunocompromised mice were used as the models of osteochondral lesions. Live imaging, macroscopic evaluation, and histological and immunohistochemical analyses were conducted at the 4- and 8-week time points.
RESULTS
Muse cell spheroids were formed, which were larger and stained more intensely with toluidine blue than non-Muse spheroids, indicating better chondrogenic differentiation. Live imaging confirmed luminescence in all 4-week model knees, but only in a few knees at 8 weeks, suggesting cell persistence. Macroscopically and histologically, no significant differences were observed between the Muse and non-Muse groups at 4 and 8 weeks; however, both groups showed better cartilage repair than that of the vehicle group at 8 weeks. No collagen type II generation was observed in the repaired tissues.
CONCLUSION
The implantation of the spheroids of Muse and non-Muse cells resulted in better healing of osteochondral lesions than that of the controls, and Muse cells had a higher chondrogenic differentiation potential than non-Muse cells.
PubMed: 38887038
DOI: 10.1177/19476035241262020 -
Journal of Bone and Mineral Research :... Jun 2024Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within...
Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within the osteochondral unit may drive OA progression. While structural-biomechanical properties of bone and cartilage have been studied, potential interaction within the osteochondral unit in the context of OA has yet to be investigated. We performed comprehensive structural and biomechanical quantification of the cartilage, subchondral bone plate, and subchondral trabecular bone using 101 osteochondral cores collected from tibial plateaus of 12 control human cadavers (CT, 5 male/7 female) and 19 patients undergoing total knee replacement (OA, 6 male/13 female). For each sample, we quantified subchondral bone plate microstructure, plate-and-rod morphological properties of the subchondral trabecular bone using individual trabecula segmentation, and morphological and compositional properties of the articular cartilage. We also performed indentation testing on each compartment of the osteochondral unit to extract the respective structural-mechanical properties. Cartilage thickness was lower in moderate and severe OA regions, while OARSI score was higher only in severe OA regions. GAG content did not change in any OA region. Aggregate and shear moduli were lower only in severe OA regions, while permeability was lower only in moderate OA regions. In the subchondral bone plate, thickness and TMD were higher in moderate and severe OA regions. Tissue modulus of subchondral trabecular bone was lower in moderate OA regions despite a thicker and more mineralized subchondral bone plate; this deterioration was not observed in severe OA regions. Regression analysis revealed strong correlations between cartilage and subchondral trabecular bone properties in CT; these correlations were also found in moderate OA regions but were not observed in severe OA regions. In summary, our findings comprehensively characterize the human OA osteochondral unit. Importantly, uncoupling cartilage and subchondral bone structural-mechanical properties may be a hallmark of OA.
PubMed: 38887013
DOI: 10.1093/jbmr/zjae094 -
Knee Surgery, Sports Traumatology,... Jun 2024The present study aimed to compare the clinical outcomes and safety at a 1-year follow-up after 5 or 6 weeks of non-weight bearing after a Talar OsteoPeriostic grafting...
PURPOSE
The present study aimed to compare the clinical outcomes and safety at a 1-year follow-up after 5 or 6 weeks of non-weight bearing after a Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC) for a medial osteochondral lesion of the talus (OLT).
METHODS
A retrospective comparative case-control analysis of prospectively followed patients who underwent a TOPIC procedure with medial malleolus osteotomy was performed. Patients were matched in two groups with either 5 or 6 weeks of non-weight bearing. Clinical outcomes were evaluated using the Numeric Rating Scale (NRS) during walking, rest, running, and stairclimbing. Additionally, the Foot and Ankle Outcome Score (FAOS) and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were assessed. Moreover, radiology and complications were assessed.
RESULTS
Eleven patients were included in the 5-week non-weight bearing group and 22 in the 6-week non-weight bearing group. No significant differences were found in any of the baseline variables. The NRS during walking in the 5-week group improved by 3.5 points and 4 points for the 6-week group (p = 0.58 at 1-year post-operatively). In addition, all other NRS scores, FAOS subscales and the AOFAS scores improved (all n.s. at 1 year follow-up). No significant differences in radiological (osteotomy union and cyst presence in the graft) were found. Moreover, no significant differences were found in terms of complications and reoperations.
CONCLUSION
No statistical significant differences were found in terms of clinical, radiological and safety outcomes between 5 or 6 weeks of non-weight bearing following a TOPIC for a medial OLT.
LEVEL OF EVIDENCE
Level III, Therapeutic.
PubMed: 38881368
DOI: 10.1002/ksa.12315 -
Arthroscopy : the Journal of... Jun 2024The new radiographic "Windshield Wiper Sign" detects hip instability and an instability-related osteochondral defect of the anterolateral femoral head. It is visible on...
The Hip "Windshield Wiper Sign": An Osteochondral Defect of the Anterolateral Femoral Head, Predicts Instability and Allows Planning of Combined Arthroscopic Cartilage Therapy and Periacetabular Osteotomy.
The new radiographic "Windshield Wiper Sign" detects hip instability and an instability-related osteochondral defect of the anterolateral femoral head. It is visible on plain radiographs, as well as MRI and during arthroscopy, in otherwise considered normal or borderline hips based on the lateral center-edge angle (LCEA). In the last two decades, femoral acetabular impingement syndrome (FAIS) with labral lesions and cartilage lesions were treated with excellent results. Recently the focus shifted to complex cases, revision surgery, and capsular management preventing postoperative hip instability. (Micro-)instability of the hip causes poor outcomes, but preoperatively there has been no Gold Standard for radiographic assessment of hip instability. On plain radiographs we use the LCEA and the anterior center-edge angle (ACEA), we can also use the Femoro-Epiphyseal Acetabular Roof (FEAR) Index and The Gothic Arch Angle (GAA). These signs help detect in which cases arthroscopic surgery alone would provide poor results and a concurrent osteotomy, for example a periacetabular osteotomy (PAO), is needed. We now understand that hip instability in hips otherwise considered normal hips or borderline dysplastic can be detected by the Windshield Wiper Sign. This is important knowledge for concomitant arthroscopic combined with osteotomy, as the need for cartilage therapy can be determined preoperatively.
PubMed: 38880183
DOI: 10.1016/j.arthro.2024.06.003