Exposure Of Cartilage Research Articles

A Patient With Exposed Costal Cartilage After Microtia Surgery Successfully Treated With Perifascial Areolar Tissue Grafting

Postoperative costal cartilage exposure is a troublesome complication following costal cartilage grafting for microtia. The authors report a case of attempted recovery using perifascial areolar tissue (PAT) transplantation that achieved favorable results. The patient was a 13-year-old boy, who developed a 27 × 11 mm2 skin ulcer with a 6 × 3.5 mm2 area of exposed cartilage at the helix 1 month after ear ablation surgery. PAT harvested from above the trapezius muscle was grafted onto the ulcer. The wound was closed 14 days later using a split-thickness skin graft from the head. PAT transplants can be harvested from anywhere in the body, are minimally invasive, and are highly flexible. This case demonstrates that, although factors such as the extent and location of cartilage exposure must be considered, PAT transplants are an option for microtia salvage surgery.

Classification of Microtia With Unusable Remnant Ear and Techniques in the First Stage of Two-Stage Auricular Reconstruction.

The remnant ear is a very important material in auricular reconstruction surgery; its dimension, position, and shape determine how it is used. However, the local conditions of microtia patients are complex and variable. Situations may be encountered where a series of abnormal remnant ears cannot be utilized in clinical practice. Currently, there are no literature that elaborates on this type of microtia and provides systematic treatment methods. The purpose of this article is to systematically classify them and optimize the two-stage method auricular reconstruction, to provide an effective surgical method for these patients. Based on the size, shape, and relative position of the residual ears, the unusable remnant ears were classified into three types: tiny size, abnormal shape, and relative position anomaly (over 1-cm higher than the contralateral earlobe). Fifty-three microtia patients with unusable remnant ear (54 ears) who underwent two-stage auricular reconstruction from August 2020 to August 2023 were reviewed. All patients had experienced earlobe reconstruction by using autologous rib cartilage during the first stage of surgery. Aesthetic assessments were evaluated from the naturalness of the earlobe reconstructed with autologous rib cartilage and the connection with the overall framework. The data on any complications that occurred during the follow-up period and patient satisfaction were collected. Among all patients, 31 had tiny size, 14 had abnormal shape, and 8 had excessively high positions. Patients were followed up for an average period of 9.2 months (6 to 12 months). No complex complications such as infection, skin necrosis, or cartilage exposure occurred. Fifty patients (94.3%) achieved excellent or good aesthetic outcomes. Fifty-one patients (96.2%) were satisfied with the reconstruction outcomes. An accurate assessment of the residual ear preoperatively is essential. Reconstructing and splicing the earlobe with autologous rib cartilage in cases where the residual ear cannot be utilized compensate for the defect that the soft tissue cannot provide the earlobe flap. This is an effective surgical method for the ear reconstruction in such patients.

Clinical Analysis and Treatment Strategies About Cartilage Scaffold Exposure After Auricular Reconstruction With the Expanded Two-Flap Method.

Objectives: Soft tissue expansion is one of the main methods for autologous cartilage auricular reconstruction. The aim of this study was to analyze the risk factors for cartilage exposure after this method and to describe a surgical method for this complication. Methods: From January 2018 to December 2020, 853 patients (908 sides) underwent auricular reconstruction with an expanded two-flap method at our center. Thirty-two patients experienced cartilage exposure postoperatively. These patients were set as the case group, and 1:1 matched sampling was performed among patients who did not have cartilage exposure. The matched sample of 32 cases was set as the control group. All 64 patients were evaluated according to the Orbit, Mandible, Ear, Nerve, and Soft tissue (OMENS) classification system to analyze the correlation between cartilage exposure and hemifacial microsomia (HFM) and OMENS subtypes. The complication was repaired with superficial temporal fascial flap combined with skin graft. Results: HFM might be a risk factor for scaffold cartilage exposure, and there was a significant correlation between cartilage exposure and orbital malformation, facial nerve dysplasia, and soft tissue developmental malformation. The use of a superficial temporal fascial flap combined with a split-thickness skin graft to repair the complication achieved satisfactory outcomes. Conclusions: There is a correlation between cartilage scaffold exposure and the severity of HFM. Temporoparietal fascial flap transfer combined with skin grafting proved to be an effective method for cartilage exposure.

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

Perifascial areolar tissue graft promotes angiogenesis and wound healing in an exposed ischemic component rabbit model.

Multiple studies have reported the use of perifascial areolar tissue (PAT) grafts to treat wounds involving exposed ischemic tissues, avascular structures, and defective membrane structures. Our objective was to assess the quantitative effects of PAT grafts and their suitability for wounds with ischemic tissue exposure and to qualitatively determine the factors through which PAT promotes wound healing and repair. We conducted histological, immunohistochemical, and mass spectrometric analyses of the PAT grafts. PAT grafts contain numerous CD34+ progenitor/stem cells, extracellular matrix, growth factors, and cytokines that promote wound healing and angiogenesis. Furthermore, we established a male rabbit model to compare the efficacy of PAT grafting with that of an occlusive dressing treatment (control) for wounds with cartilage exposure. PAT grafts could cover ischemic components with granulation tissue and promote angiogenesis. Macroscopic and histological observations of the PAT graft on postoperative day seven revealed capillaries bridging the ischemic tissue (vascular bridging). Additionally, the PAT graft suppressed wound contraction and alpha smooth muscle actin (αSMA) levels and promoted epithelialization. These findings suggested that PAT can serve as a platform to enhance wound healing and promote angiogenesis. This is the first study to quantify the therapeutic efficacy of PAT grafts, revealing their high value for the treatment of wounds involving exposed ischemic structures. The effectiveness of PAT grafts can be attributed to two primary factors: vascular bridging and the provision of three essential elements (progenitor/stem cells, extracellular matrix molecules, and growth factors/cytokines). Moreover, PAT grafts may be used as transplant materials to mitigate excessive wound contraction and the development of hypertrophic scarring.

Salvage of Extensive Skin Graft Necrosis After Auricle Reconstruction by Using Modified Nagata Method.

Extensive skin graft necrosis after auricle reconstruction surgery is a thorny problem for plastic surgeons. Four unilateral microtia patients were enrolled for extensive skin graft necrosis after ear elevation surgery. Early debridement and daily dressing changes were important for preoperative preparation. Surgical treatments involved local flaps and secondary split-thickness skin graft. After 3 to 12 months of follow-up, clear surface structures and obvious auricular sulcus were shown in all 4 patients. No cartilage exposure, skin necrosis, healing impairment, or other complications were found. We attribute the cause of extensive skin graft necrosis to subcutaneous hematoma. Local skin flaps and split-thickness skin grafting can be effective treatments for such situations. The use of temporoparietal fascial flap is unnecessary when poor graft survival is caused by subcutaneous hematoma.

A Retrospective Study on the Reconstruction of Nasal Septal Mucosal Defects after Asian Rhinoplasty.

Nasal septal mucosal defects following rhinoplasty in Asian patients are uncommon complications. However, the reconstruction of such defects presents a challenging task in plastic surgery. The aim of this study was to present comprehensive surgical strategies for the reconstruction of nasal septal mucosal defect after rhinoplasty. Thirteen cases presenting with nasal septal mucosal defects between January 2016 and October 2021 were retrospectively reviewed. The size, location, and severity of the defect as well as the extent of cartilage exposure were taken into consideration during evaluation, and surgical approaches were employed for repair accordingly. Patient satisfaction was evaluated using a questionnaire with visual analog scale (VAS) and nasal obstruction symptom evaluation scale (NOSE). The average postoperative follow-up period in this study group was 10.15 months. Reconstruction of nasal septal mucosal defects resulted in successful treatment for all patients. There was no evidence of flap failure or nasal valve stenosis. All patients were satisfied with the reconstruction outcome. The successful application of surgical techniques for nasal septal mucosal defects after rhinoplasty requires comprehensive consideration. The utilization of the retrograde-flow superior labial artery mucosal flap appears to be a secure, efficient, and effective technique for nasal septal mucosal defect reconstruction in rhinoplasty, particularly in cases with cartilage exposure. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Brent Technique of Repair Versus Nagata Auricular Reconstruction for Microtia Reconstruction: A Systematic Review and Meta-Analysis.

Up to 17.4 in every 10,000 births are affected by microtia, but no consensus exists on a gold standard technique for autogenous repair. In this study, the authors compare 2 common methods-the Brent and Nagata autogenous costal cartilage ear reconstruction techniques. A systematic review of the literature and a quantitative meta-analysis to compare the outcomes of these 2 approaches were performed. The outcomes analyzed included rates of infection, necrosis, cartilage exposure, cartilage resorption, hematoma, wire extrusion, and hypertrophic scar. A MEDLINE database systematic review with the following keywords: microtia, Brent, and Nagata was performed. Case reports and articles without original data or patient outcomes were excluded. Inclusion methods for study selection are outlined in Supplemental Digital Content 1, http://links.lww.com/SCS/F461 , below. The prevalence of outcomes for each study was analyzed through meta-analysis of proportions using Stata. A total of 536 potential studies were retrieved for review. Twelve of these studies met inclusion criteria. Four studies utilized the Brent method of repair with the inclusion of 563 ear reconstructions. Nine studies implemented the Nagata technique in 2304 reconstructions. Two studies directly compared the Brent (327 ears) and Nagata (471 ears) techniques. The calculated rate and 95% confidence intervals are summarized in Supplemental Digital Content 2, http://links.lww.com/SCS/F461 . There were no statistically significant differences in complication rates between the Brent and Nagata microtic reconstruction techniques identified in this study. The Brent and Nagata microtia reconstruction techniques have no difference in the risk of infection, necrosis, cartilage exposure, cartilage resorption, hematoma, wire extrusion, or hypertrophic scars.

Primary Ear Reconstruction Using Cadaveric Costal Cartilage.

Allogeneic cadaveric costal cartilage is commonly used for grafts in nasal reconstruction surgery; however, limited information exists on its use in total ear reconstruction for microtia. In this case series, we describe the novel use of cadaveric cartilage for auricular framework construction in ear reconstruction and review preliminary histologic findings. Patients requiring primary complete reconstruction of the auricle from August 2020 to December 2021 were eligible and underwent ear reconstruction using cadaveric costal cartilage. Patients were evaluated for surgical site infection, skin necrosis, cartilage resorption, and cartilage exposure during regular follow-up visits. Two cartilage samples were taken after 2 separate second-stage surgeries done 52 weeks after first-stage reconstruction. These samples were stained with hematoxylin and eosin as well as safranin-O and examined under light microscopy. A total of 12 ear reconstruction procedures using cadaveric costal cartilage were performed across 11 patients; 10 of 12 ears had type III microtia and 2 of 12 ears had type IV microtia. Patients ranged from 4 to 25 years old at the time of surgery, with an average age of 10.7 years. Follow-up time ranged from 1.6 to 25.4 months, with a mean follow-up time of 11.2 months. No patients experienced any visibly significant cartilage warping. Two patients experienced minor construct exposure, which were successfully salvaged. Two patients experienced surgical site infections, one lead to resorption requiring framework replacement. Preliminary histologic analysis of the 2 samples taken 1 year after implantation showed viable chondrocytes with no evidence of immunologic rejection or any local inflammation or host foreign body response. Cadaveric costal cartilage serves as a viable alternative to autologous cartilage and other alloplastic biomaterials for construction of auricular frameworks in primary microtia reconstruction. Resorption secondary to infection and construct exposure remain potential risks. Longer follow-up times and a larger sample size are needed for assessment of long-term efficacy.

Strategies of Total Auricular Reconstruction for Patients With Poor Skin Coverage at the Mastoid Area.

Burns and injuries can lead to massive defects in the mastoid tissues, which increase the difficulty of ear reconstruction. It is crucial to choose an appropriate surgical method for these patients. Here, we introduce strategies for auricular reconstruction in patients without satisfactory mastoid tissues. From April 2020 to July 2021, 12 men and 4 women were admitted to our institution. Twelve patients were severely burned, 3 patients experienced car accidents, and 1 patient had a tumor on his ear. The temporoparietal fascia was used for ear reconstruction in 10 cases, and the upper arm flap was used in 6 cases. All of the ear frameworks were made of costal cartilage. The location, size, and shape of both sides of the auricles were generally the same. Two patients needed further surgical repair because of cartilage exposure at the helix. All of the patients were satisfied with the outcome of the reconstructed ear. For patients with ear deformity and poor skin coverage in the mastoid area, we can choose the temporoparietal fascia if the patient's available superficial temporal artery is longer than 10cm. If not, we can choose the upper arm flap. The latter needs a five-stage operation, which is more time consuming and difficult than the former. Moreover, the expanded upper arm flap is thinner and has better elasticity than the temporoparietal fascia, so the shape of the reconstructed ear is better. We need to evaluate the condition of the affected tissue and choose the appropriate surgical method to achieve a good result.

Fascial turnover flap - an effective method to resolve cartilage exposure after autologous microtia reconstruction

Introduction. Microtia presents a congenital ear deformity ranging from a minor and barely visible defect to a complete absence of the ear. Currently, there are three options for ear reconstruction: autologous costal cartilage, silicon prothesis, and prosthetic ear. Ear reconstruction with autologous costal cartilage is usually performed in two stages. During the first stage, the cartilaginous framework is fabricated and placed under the skin, in the anatomical position of the ear. In the second stage, the elevation of the frame is performed. During these procedures, complications such as vascular compromise of the skin envelope can occur. Cartilage exposure can lead to its resorption and distortion, leading to an unsatisfactory anatomical result, and this should be resolved as soon as possible. Cartilage exposure at the convex part of the frame is especially problematic. The goal of this paper is to show that fascial turnover flap is a safe method to deal with cartilage exposure as a complication. Outlines of cases. We present two patients with anotia and hemifacial microsomia. Both underwent autologous cartilage microtia repair. In both patients, the cartilage exposure at the convex part of the ear was revealed as a complication. Fascial turnover flap has been used to resolve this complication in both patients. Conclusion. Fascial turnover flap is a safe method to deal with cartilage exposure after microtia reconstruction with autologous cartilage.

A Two-Stage Method for Adult Congenital Microtia: The Essentials of 15-Year Experience.

Treatment of congenital microtia in adults remains challenging due to the unique physiological characteristics of the costal cartilages and retroauricular skin, which interfere with obtaining a satisfactory aesthetic result; thus, different perspectives and technical modifications during treatment are warranted. This article aims to present complementary new information and essential tips to refine the surgical technique in adult microtia reconstruction. A total of 346 adult microtia patients underwent surgical intervention at the Auricular Reconstruction Center of Plastic Surgery Hospital (Beijing, China) between 2006 and 2021. Each patient underwent a rigorous preoperative evaluation and stages one and two surgeries. Patients were followed in our clinic for 6 months to 10 years (average: 15.3 months). The postoperative complication rate was 8.1%, which included cartilage exposure, broken helix, local hematoma, infection, poor skin graft survival, and scar hypertrophy. Our results showed that the two-stage treatment strategy for adults is versatile, reliable, and effective for the treatment of congenital microtia. 4 Laryngoscope, 133:2148-2153, 2023.

Structural-Functional Pluralistic Modification of Silk Fibroin via MOF Bridging for Advanced Wound Care.

Silk fibroin (SF) is widely used to fabricate biomaterials for skin related wound caring or monitoring, and its hydrogel state are preferred for their adaptability and easy to use. However, in-depth development of SF hydrogel is restricted by their limited mechanical strength, increased risk of infection, and inability to accelerate tissue healing. Therefore, a structure-function pluralistic modification strategy using composite system of metal organic framework (MOF) as bridge expanding SF's biomedical application is proposed. After developing the photocuring and bonding SF hydrogel, a MOF drug-loading system is utilized to enhance hydrogel's structural strength while endowing its antibacterial and angiogenic properties, yielding a multifunctional SF hydrogel. The synergy between the MOF and SF proteins at the secondary structure level gives this hydrogel reliable mechanical strength, making it suitable for conventional wound treatment, whether for closing incisions quickly or acting as adhesive dressings (five times the bonding strength of ordinary fibrin glue). Additionally, with the antibacterial and angiogenic functions getting from MOF system, this modified SF hydrogel can even treat ischemic trauma with cartilage exposure. This multiple modification should contribute to the improvement of advanced wound care, by promoting SF application in the production of tissue engineering materials.

Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model

BackgroundOsteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis.MethodsAn equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2− production. To identify the underlying molecular actors, stable isotope-labeling by amino acids in cell culture based secreted protein analyses were conducted, in the presence of serum. The relative abundance of highly sequenced proteins was finally confirmed by western blot.ResultsCo-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses.ConclusionsThese results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion.Graphical abstractmdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.

Auricular Framework Construction Using Cadaveric Costal Cartilage in Type III Microtia: Preliminary Results.

Non/minimally irradiated Cadaveric Costal Cartilage (NCCC) is commonly used for grafts in nasal reconstruction; however, no information exists on its use in total ear reconstruction for type III microtia. In this case series we describe preliminary results from the novel use of NCCC for auricular framework construction in 7 ear reconstructions. Patients requiring total ear reconstruction from August 2020 to October 2021 were eligible and underwent ear reconstruction using NCCC from MTF Biologics (Edison, NJ). Patients were evaluated for surgical site infection, skin necrosis, cartilage exposure, warping, and resorption during regular follow up visits. Seven ears were reconstructed using NCCC across 5 patients with type III microtia. Patients ranged from 5 to 51 years old at the time of surgery. Follow up time ranged from 12 to 78 weeks (mean: 46wk). No patients experienced surgical site infections or significant cartilage resorption. All procedures were done outpatient, total time under anesthesia was <90 minutes in 5/7 cases and postoperative narcotics for pain management were not needed in 5/7 cases. Complications included minor skin necrosis that was repaired via primary closure, construct exposure in the immediate postoperative period, which was successfully salvaged with a local flap, and explantation of one construct after reconstruction for a complicated revision surgery involving a previous temporoparietal fascial flap. NCCC serves as an immediately available alternative to alloplastic and autologous materials for construction of auricular frameworks during ear reconstruction. Longer follow up times and a larger sample size will further elucidate long-term efficacy.

Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1-induced inflammation.

The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 (IL-1) disrupted circadian rhythms and degraded the cartilage matrix. All three inflammation-resistant approaches showed protection against IL-1–induced degradation and loss of circadian rhythms. These synthetic gene circuits reveal a unique approach to support daily rhythms in cartilage and provide a strategy for creating cell-based therapies to preserve the circadian clock.

Salvage of Ear Framework Exposure Following Autologous Microtia Reconstruction: Repair Strategy for Each Location of Exposure.

One of the most common complications of total auricular reconstruction is exposure of the ear framework. Various reconstruction methods have been reported depending on the location and size of exposed cartilage. This report describes a safe reconstruction method for each exposed part of the grafted ear framework. From January 2019 to August 2021, 2 cases (4 areas) of framework exposure were observed following autologous microtia reconstruction. The first case developed 2 small areas of skin necrosis on the anterior helix and lower antihelix to concha. The former was reconstructed with a temporal fascia flap and the latter with a local transposition flap. The second case also developed 2 small areas of skin necrosis on the posterior helix and lower antihelix to concha. The former was sutured directly and the latter with a local transposition flap. However, both wounds recurred due to flap necrosis and the cartilage was exposed again. The 3rd operation was performed by covering both wounds with a posterior auricular turnover flap and skin graft. In both cases, the exposed framework was completely covered with the flaps, and the reconstructed ears showed well-defined convolutions. Covering exposed cartilage with a local flap with a random pattern of blood circulation is convenient because no additional skin grafts are required. However, the blood circulation of the flaps is inadequate when an elongated flap is required; consequently, flap necrosis may occur. On the other hand, a temporal fascia flap and posterior auricular flap, which have axillary pattern blood circulation, are considered to be safer. We believe that it is safe to use a temporal fascia flap for cartilage exposure in the upper half of the auricle, and a posterior auricular turnover flap for the lower half.

Intra-Articular Synovial Fluid With Hematoma After Ankle Fracture Promotes Cartilage Damage In Vitro Partially Attenuated by Anti-Inflammatory Agents.

Intra-articular ankle fracture (IAF) causes posttraumatic osteoarthritis (PTOA), but the exact mechanism is unknown. Proinflammatory mediators have been shown to be present in the synovial fluid fracture hematoma (SFFH) but have not been linked to cartilage damage. The purpose of this study was to determine if the SFFH causes cartilage damage and whether this damage can be attenuated by commercially available therapeutic agents. Synovial fluid was obtained from 54 IAFs and cultured with cartilage discs from the dome of fresh allograft human tali and randomly assigned to one of the following groups: (A) control-media only, (B) SFFH from days 0 to 2 after fracture, (C) SFFH from days 3 to 9, (D) SFFH from days 10 to 14, (E) group B + interleukin 1 receptor antagonist (IL-1Ra), and (F) group B + doxycycline. The cartilage discs underwent histological evaluation for cell survival and cartilage matrix components. The spent media were analyzed for inflammatory mediators. Cartilage discs cultured with SFFH in groups B, C, and D demonstrated significantly increased production of cytokines, metalloproteinases (MMPs), and extracellular matrix breakdown products. Safranin O staining was significantly decreased in group B. The negative effects on cartilage were partially attenuated with the addition of either IL-1RA or doxycycline. There was no difference in chondrocyte survival among the groups. Exposure of uninjured cartilage to IAF SFFH caused activation of cartilage damage pathways evident through cartilage disc secretion of inflammatory cytokines, MMPs, and cartilage matrix fragments. The addition of IL-1Ra or doxycycline to SFFH culture partially attenuated this response. IAFs create an adverse intra-articular environment consisting of significantly increased levels of inflammatory cytokines and MMPs able to damage cartilage throughout the joint. These data suggest that the acute addition of specific inflammatory inhibitors may decrease the levels of these proinflammatory mediators.

A possible issue of articular cartilage degeneration in acute phase after anterior cruciate ligament reconstruction

A possible issue of articular cartilage degeneration in acute phase after anterior cruciate ligament reconstruction

Musculoskeletal complications associated with pathological iron toxicity and its molecular mechanisms.

Iron is fundamental for several biological functions, but when in excess can lead to the development of toxic events. Some tissues and cells are more susceptible than others, but systemic iron levels can be controlled by treating patients with iron-chelating molecules and phlebotomy. An early diagnostic can be decisive to limit the progression of musculoskeletal complications like osteoarthritis and osteoporosis because of iron toxicity. In iron-related osteoarthritis, aggravation can be associated to a few events that can contribute to joints articular cartilage exposure to high iron concentrations, which can promote articular degeneration with very little chance of tissue regeneration. In contrast, bone metabolism is much more dynamic than cartilage, but progressive iron accumulation and ageing can be decisive factors for bone health. The iron overload associated with hereditary diseases like hemochromatosis, hemophilias, thalassemias and other hereditary anaemias increase the negative impact of iron toxicity in joints and bone, as well as in life quality, even when iron levels can be controlled. The molecular mechanisms by which iron can compromise cartilage and bone have been illusive and only in the last 20 years studies have started to shed some light into the molecular mechanisms associated with iron toxicity. Ferroptosis and the regulation of intracellular iron levels is instrumental in the balance between detoxification and induced cell death. In addition, these complications are accompanied with multiple susceptibility factors that can aggravate iron toxicity and should be identified. Therefore, understanding tissues microenvironment and cell communication is fundamental to contextualize iron toxicity.