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Foot and Ankle Clinics Jun 2024The last several decades have brought about substantial development in our understanding of the biomolecular pathways associated with chondral disease and progression to... (Review)
Review
The last several decades have brought about substantial development in our understanding of the biomolecular pathways associated with chondral disease and progression to arthritis. Within domains relevant to foot and ankle, genetic modification of stem cells, augmentation of bone marrow stimulation techniques, and improvement on existing scaffolds for delivery of orthobiologic agents hold promise in improving treatment of chondral injuries. This review summarizes novel developments in the understanding of the molecular pathways underlying chondral damage and some of the recent advancements within related therapeutics.
Topics: Humans; Cartilage, Articular; Cartilage Diseases
PubMed: 38679445
DOI: 10.1016/j.fcl.2023.08.002 -
Journal of Pediatric Orthopedics Feb 2024Previous research on patellar and trochlear groove osteochondritis dissecans (OCD) is limited by small sample sizes. This study aims to describe the presentation of...
OBJECTIVE
Previous research on patellar and trochlear groove osteochondritis dissecans (OCD) is limited by small sample sizes. This study aims to describe the presentation of patients with OCD lesions of the patella and trochlea and characterize the outcomes of operative and nonoperative treatments.
METHODS
This retrospective cohort study identified all patients from a single institution from 2008 to 2021 with patellar and/or trochlear OCD lesions. Patients were excluded from the study if surgical records were unavailable or if the patient had knee surgery for a different injury at index surgery or in the 12 months postoperative. Minimum follow-up was 12 months. Outcomes included a return to sports (RTS), pain resolution, radiographic healing, and treatment "success" (defined as full RTS, complete pain resolution, and full healing on imaging).
RESULTS
A total of 68 patients (75 knees) were included-45 (60%) with patellar OCD and 30 (40%) with trochlear. Of the patients, 69% were males. The median age at knee OCD diagnosis was 14 years. At the final follow-up, 62% of knees (n = 44) recovered sufficiently to allow a full RTS and 54% of knees (n = 39) had full pain resolution. Of the 46 knees with radiographic imaging at least 1 year apart, 63% had full healing of the lesion. There was no significant difference in RTS, pain resolution, radiographic healing, or overall success when comparing treatments.
CONCLUSIONS
This study provides valuable epidemiologic demographic and outcome data regarding the scarcely reported patellar and trochlear OCD. While over half of patients fully returned to sports and reported full pain resolution, a large proportion continued to experience symptoms over a year after presentation. Future research should aim to better define the treatment algorithms for these OCD subtypes.
LEVEL OF EVIDENCE
Level III.
Topics: Male; Humans; Adolescent; Female; Osteochondritis Dissecans; Patella; Retrospective Studies; Pain; Knee Joint; Demography
PubMed: 38108383
DOI: 10.1097/BPO.0000000000002588 -
Journal of Cellular Physiology Nov 2023Temporomandibular joint (TMJ) osteoarthritis (OA) is a common type of TMJ disorders causing pain and dysfunction in the jaw and surrounding tissues. The causes for TMJ...
Temporomandibular joint (TMJ) osteoarthritis (OA) is a common type of TMJ disorders causing pain and dysfunction in the jaw and surrounding tissues. The causes for TMJ OA are unknown and the underlying mechanism remains to be identified. In this study, we generated genetically-modified mice deficient of two homologous microRNAs, miR-204 and miR-211, both of which were confirmed by in situ hybridization to be expressed in multiple TMJ tissues, including condylar cartilage, articular eminence, and TMJ disc. Importantly, the loss-of-function of miR-204 and miR-211 caused an age-dependent progressive OA-like phenotype, including cartilage degradation and abnormal subchondral bone remodeling. Mechanistically, the TMJ joint deficient of the two microRNAs demonstrated a significant accumulation of RUNX2, a protein directly targeted by miR-204/-211, and upregulations of β-catenin, suggesting a disrupted balance between osteogenesis and chondrogenesis in the TMJ, which may underlie TMJ OA. Moreover, the TMJ with miR-204/-211 loss-of-function displayed an aberrant alteration in both collagen component and cartilage-degrading enzymes and exhibited exacerbated orofacial allodynia, corroborating the degenerative and painful nature of TMJ OA. Together, our results establish a key role of miR-204/-211 in maintaining the osteochondral homeostasis of the TMJ and counteracting OA pathogenesis through repressing the pro-osteogenic factors including RUNX2 and β-catenin.
Topics: Animals; Mice; beta Catenin; Cartilage, Articular; Chondrocytes; Core Binding Factor Alpha 1 Subunit; MicroRNAs; Osteoarthritis; Temporomandibular Joint Disorders
PubMed: 37697972
DOI: 10.1002/jcp.31120 -
Stem Cell Reviews and Reports Aug 2023Orthopedic surgeons face a lot of difficulties in managing and repairing osteochondral defects. Damaged articular cartilage and the subchondral bone underneath are both... (Review)
Review
Orthopedic surgeons face a lot of difficulties in managing and repairing osteochondral defects. Damaged articular cartilage and the subchondral bone underneath are both present in osteochondral defects. The demands of the bone, cartilage, and the contact between the bone and the cartilage must be taken into consideration while repairing an osteochondral defect. Only palliative, not curative, therapeutic interventions are now available for the healing of osteochondral abnormalities. With its ability to successfully rebuild bone, cartilage, and the junction between bone and cartilage, tissue engineering has been recognized as an effective substitute. In correlation, mechanical stress and physical processes are commonly applied to the osteochondral area. Therefore, the ability of chondrocytes and osteoblasts to regenerate is influenced by bioactive molecules and the physicochemical characteristics of the surrounding matrix. The treatment of osteochondral disorders is said to benefit from the use of stem cells as an alternative intervention. In the field of tissue engineering, various approaches have been used such as the direct implantation of scaffolding materials at the site of tissue injury in patients, either alone or loaded with cells and bioactive molecules at the target site to imitate the natural extracellular matrix. Despite the extensive use and advancements of tissue-engineered biomaterials such as natural and synthetic polymer-based scaffolds, their repair capacity is limited due to challenges in combating antigenicity, designed to simulate in vivo microenvironment, and conducting mechanical or metabolic characteristics comparable to native organs/tissues. This study explores numerous osteochondral tissue engineering methodologies focusing on scaffold design, material varieties, manufacturing techniques, and functional features. This review is focused on recent breakthroughs in bioactive scaffolds that aid osteogenic and chondrogenic differentiation for bone and cartilage repair. The topic will cover fundamental anatomy, osteochondral repair methodologies and obstacles, cell selection, biochemical variables, and bioactive materials, as well as the design and manufacture of bioactive scaffolds. Additionally, we focus on the concept and construction of decellularized scaffolds, and the fabrication of dECM scaffolds in tissue engineering from various skin, bone, nerve, heart tissue, lung, liver, and kidney, and their application in osteochondral regeneration.
Topics: Humans; Tissue Engineering; Tissue Scaffolds; Regenerative Medicine; Cartilage, Articular; Chondrocytes
PubMed: 37074547
DOI: 10.1007/s12015-023-10545-x -
Acta Biomaterialia Oct 2023The incidence of osteochondral defect is increasing year by year, but there is still no widely accepted method for repairing the defect. Hydrogels loaded with bioactive...
The incidence of osteochondral defect is increasing year by year, but there is still no widely accepted method for repairing the defect. Hydrogels loaded with bioactive molecules have provided promising alternatives for in-situ osteochondral regeneration. Kartogenin (KGN) is an effective and steady small molecule with the function of cartilage regeneration and protection which can be further boosted by TGF-β. However, the high cost, instability, and immunogenicity of TGF-β would limit its combined effect with KGN in clinical application. In this study, a composite hydrogel CM-KGN@GelMA, which contained TGF-β1 analog short peptide cytomodulin-10 (CM-10) and KGN, was fabricated. The results indicated that CM-10 modified on GelMA hydrogels exerted an equivalent role in enhancing chondrogenesis as TGF-β1, and this effect was also boosted when combined with KGN. Moreover, it was revealed that CM-10 and KGN had a synergistic effect on promoting the chondrogenesis of BMSCs by up-regulating the expression of RUNX1 and SOX9 at both mRNA and protein levels in vitro. Finally, the composite hydrogel exhibited a satisfactory osteochondral defect repair effect in vivo, showing similar structures close to the native tissue. Taken together, this study has revealed that CM-10 may serve as an alternative for TGF-β1 and can collaborate with KGN to accelerate chondrogenesis, which suggests that the fabricated CM-KGN@GelMA composite hydrogel can be acted as a potential scaffold for osteochondral defect regeneration. STATEMENT OF SIGNIFICANCE: Kartogenin and TGF-β have shown great value in promoting osteochondral defect regeneration, and their combined application can enhance the effect and show great potential for clinical application. Herein, a functional CM-KGN@GelMA hydrogel was fabricated, which was composed of TGF-β1 mimicking peptide CM-10 and KGN. CM-10 in hydrogel retained an activity like TGF-β1 to facilitate BMSC chondrogenesis and exhibited boosting chondrogenesis by up-regulating RUNX1 and SOX9 when being co-applied with KGN. In vivo, the hydrogel promoted cartilage regeneration and subchondral bone reconstruction, showing similar structures as the native tissue, which might be vital in recovering the bio-function of cartilage. Thus, this study developed an effective scaffold and provided a promising way for osteochondral defect repair.
Topics: Hydrogels; Transforming Growth Factor beta1; Core Binding Factor Alpha 2 Subunit; Tissue Scaffolds; Mesenchymal Stem Cells; Peptides; Chondrogenesis
PubMed: 37586447
DOI: 10.1016/j.actbio.2023.08.013 -
Foot and Ankle Clinics Jun 2024Although most commonly found in the knee, elbow, and talar dome, osteochondral lesions can also be found in the subtalar joint and can occur due to either high or low... (Review)
Review
Although most commonly found in the knee, elbow, and talar dome, osteochondral lesions can also be found in the subtalar joint and can occur due to either high or low energy trauma. Diagnosis of these lesions in the subtalar joint is typically confirmed with advanced imaging such as computerized tomography and MRI. Although there are a few published case reports, there is otherwise very limited literature on the prevalence, treatment options, prognosis, or outcomes for patients with osteochondral lesions of the subtalar joint, and thus further research is required in this area.
Topics: Humans; Subtalar Joint; Prognosis; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Cartilage, Articular
PubMed: 38679435
DOI: 10.1016/j.fcl.2023.07.002 -
Foot and Ankle Surgery : Official... Dec 2023Platelet-rich plasma (PRP) is an autologous serum containing higher concentrations of platelets and growth factors above normal blood. The process of obtaining PRP... (Review)
Review
Platelet-rich plasma (PRP) is an autologous serum containing higher concentrations of platelets and growth factors above normal blood. The process of obtaining PRP involves the extraction of blood from the patient which is then centrifuged to obtain a concentrated suspension of platelets. PRP continues to evolve as a potential treatment modality with many applications in orthopaedic surgery. The therapeutic components of PRP possess numerous theoretical regenerative properties. The present manuscript outlines how PRP is prepared, noting the tremendous variability between preparation protocols. Given the growing body of evidence examining the use of PRP in pathologies of the foot and ankle, we assess its efficacy as it relates to our field. Specifically, we evaluate the literature in the past five years regarding the role of PRP in treating plantar fasciitis, Achilles tendinopathy, insertional Achilles tendinitis, Achilles tendon ruptures, osteochondral lesions of the talus, hallux rigidus, and ankle osteoarthritis.
Topics: Humans; Ankle; Achilles Tendon; Tendinopathy; Tendon Injuries; Platelet-Rich Plasma; Treatment Outcome
PubMed: 37516651
DOI: 10.1016/j.fas.2023.07.010 -
Bioactive Materials Sep 2023Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and... (Review)
Review
Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.
PubMed: 37180643
DOI: 10.1016/j.bioactmat.2023.04.016 -
Diagnostics (Basel, Switzerland) Apr 2024Osteochondritis dissecans (OCD) of the elbow mainly occurs in overhead athletes (OHAs). This narrative review aimed to comprehensively analyze the epidemiological data,... (Review)
Review
Osteochondritis dissecans (OCD) of the elbow mainly occurs in overhead athletes (OHAs). This narrative review aimed to comprehensively analyze the epidemiological data, etiological factors, clinical and imaging features, treatment options, and outcomes of OHAs with the diagnosis of elbow OCD. A literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science. Individuals with elbow OCD were usually 10-17 years of age with incidence and prevalence varying between studies, depending on the sport activity of the patients. The etiology of OCD lesions is multifactorial, and the main causes are believed to be repetitive trauma, the biomechanical disproportion of the articular surfaces, poor capitellar vascular supply, and inflammatory and genetic factors. Athletes usually presented with elbow pain and mechanical symptoms. The mainstay for the diagnosis of elbow OCD is MRI. The treatment of elbow OCD lesions should be conservative in cases of stable lesions, while various types of surgical treatment are suggested in unstable lesions, depending mainly on the size and localization of the lesion. The awareness of medical practitioners and the timely diagnosis of OCD lesions in OHAs are key to favorable outcomes.
PubMed: 38732330
DOI: 10.3390/diagnostics14090916