Lumbar instability remodels cartilage endplate to induce intervertebral disc degeneration by recruiting osteoclasts via Hippo-CCL3 signaling

Degenerated endplate appears with cheese-like morphology and sensory innervation,contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However,the origin and development mechanism of the cheese-like morphology remain unclear.Here in this study,we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change.

Current practice in autologous rib and costal-cartilage harvest for rhinoplasty:A systematic review

Background:Autologous costal grafts are used universally in clinical practice for rhinoplasty and reconstruction.However,surgeons worldwide have not agreed on the details of graft harvesting,including rib selection,side preference,operation mode,cutting methods,and handling of the periosteum and perichondrium.This study aimed to provide an overview of the novel techniques used for auto-rib harvesting in rhinoplasty within the past 5 years and identify potential avenues for future research.Methods:We searched for related articles in PubMed,Embase,and Web of Science from 2019 to 2023,summa-rized crucial but controversial steps in recent practice,and analyzed their theoretical basis and clinical feasibility.Results:Auto-rib and cartilage open harvest is still mainstream in rhinoplasty and reconstruction,with the 5th to 8th ribs and cartilage being the most used.The laparoscopic harvest is gaining attention,being second only to the open harvest,with the 9th/10th ribs and cartilages being particularly convenient.The clinical applications of full-cut and split-cut methods differ in their advantages.Except for some special reasons,almost all studies tended to preserve the periosteum and perichondrium in situ,and few surgeons chose to harvest the grafts on the left side.Conclusion:Multiple techniques have emerged,requiring surgeons to balance the benefits and risks of various strategies at each step.New theories and techniques should be fully tested promptly and in clinical practice before wide application.Overall,a professional consensus is needed for better directivity,precision,and stability in clinical practice.

Ear keloid and epidermal cyst following auricular cartilage harvest for rhinoplasty:A case report

BACKGROUND This case report highlights a rare instance of concurrent keloid and epidermal cyst development at an ear cartilage harvest site following rhinoplasty in a 25-year-old woman.Both conditions,which typically stem from skin trauma,seldom occur together,demonstrating the exceptional characteristics of this case.CASE SUMMARY The patient underwent successful surgical removal of both the keloid and the epidermal cyst.Postoperative treatment included the use of silicone sheets,gel,and oral tranilast to reduce scarring.No recurrence was observed over a 6-mo follow-up period,indicating effective management of the condition.CONCLUSION The effective management of complex skin trauma cases underscores the need for individualized treatment strategies in plastic surgery.

Interlayer repair with porcine small intestinal submucosa versus internal repair with tragus cartilage in endoscopic tympanoplasty

Objective Endoscopic tympanoplasty includes various surgical methods,such as internal repair,interlayer repair,and external overlay.This technique requires autologous materials,allografts,and xenografts,which are used to repair tympanic membrane(TM)perforation.To obtain good results,appropriate surgical methods and repair materials should be selected.This study aims to assess the efficacy of repairing refractory TM perforations in the porcine small intestinal submucosa(SIS)during transcanal endoscopic type I tympanoplasty.Method A retrospective chart review was performed on patients who underwent TM perforation repair with porcine SIS and tragus cartilage between January 2022 and September 2022 at Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.Perforation size,tympanic status,pre-and postoperative symptoms,follow-up data,wound healing rates,and hearing improvement were analysed.Results Of the 115 patients included in the study,56 underwent interlayer repair with porcine SIS of the TM,and 59 patients underwent internal repair with tragus cartilage.No significant difference was found between the two groups at baseline in terms of age,sex,disease course,perforation side,tympanic status,underlying disease,or preoperative infection.The total postoperative effective rate of interlayer implantation with porcine SIS was 91.07%(51 patients),and that of internal implantation with tragus cartilage was 88.14%(52 patients).No significant difference was found in terms of the graft success rate between the two surgical methods(p=0.887).Postoperative pure tone auditory(PTA)and air-bone gap(ABG)density significantly increased in both groups compared with before surgery(p<0.05).However,the postoperative PTA and ABG density were not significantly different 3 months post-surgery between the two groups(p>0.05).Compared to those in the internal implantation group,the patients in the interlayer group had a shorter operation duration(51.36±6.76 min vs.59.71±7.45 min,t=6.298,p<0.001)and less blood loss(11.91±2.61 mL vs.15.27±2.57 mL,t=7.019,p<0.001).Conclusions Our study suggests that the porcine SIS,as well as the tragus cartilage,has a high success rate in repairing irreversible TM perforation.Endoscopic tympanoplasty via interlayer implantation with porcine SIS offers distinct advantages,including the absence of donor-site incision and scar formation,and ease of graft modification and manipulation.

Clinical study on improving the diagnostic accuracy of adult elbow joint cartilage injury by multisequence magnetic resonance imaging

BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.

Donor-Site Morbidity Following Harvest of Autologous Costal Cartilage in Microtia Reconstruction

Objectives: The objective of this study is to evaluate donor-site morbidity after costal cartilage harvest for microtia reconstruction. Methods: A total of 70 patients who underwent autologous costal cartilage harvest for microtia reconstruction from March 2008-March 2009 were included. Anterior chest wall deformity was evaluated with chest topography, and scar quality at baseline and at 6-months follow-up, and final outcomes analyzed with SPSS. Results: In 70 patients, 52 (74%) were male, 18 (26%) were female, and altogether 40 (57%) patients developed deformity. At 6-month follow-up, the incidence of anterior chest wall deformity was highest at 80% in Block-III, and least at 0% in Block-I. The 6 - 10 years age group was the largest group at 84% (21), and also with highest incidence of deformity in association to Block-IV harvest at 83%. The incidence of donor-site deformity was higher in female gender at 66%, and 54% in males. But in the sub-group, male had higher incidence of deformity at 75% in both Block-III, and Block-IV when compared to the respective females. The 120 - 135 cm height group had the highest deformity at 67% with Block-IV costal cartilages harvested. At the three measurement points: 1) xiphisternum, 2) intersecting points between PSL and LCM, and 3) intersecting points between MCL and LCM, significant differences (mean) were observed in chest circumference from baseline to 6-month follow-up, and between the left and right chest hemi-circumference (postoperatively). Acceptable donor-site scar was observed in all but 3% (2) developed hypertrophic scar. Conclusion: The development of chest wall deformity was observed when more than one costal cartilage was harvested, particularly the 6th (complete), 7th, 8th block. Therefore, to minimize the deformity, we recommend harvesting only the necessary amount of cartilage, and at the lowest level possible to avoid injury of costochondral junction. Additionally, age, height, gender and chest development are equally important factors which influence donor-site deformity in microtia reconstruction.

Endoscopic push through tragal cartilage tympanoplasty: A 10-year retrospective review of our technique and outcomes

BACKGROUND Endoscopic ear surgery(EES)provides a magnified,high-definition view of the otological surgical field.EES allows otologists to avoid surgical incisions and associated postoperative complications.It is an ideal technique for the perfor-mance and teaching of tympanoplasty.AIM To examine the efficacy of total Endoscopic Push Through Tragal Cartilage Tympanoplasty(EPTTCT),at our institution over a 10-year period.METHODS A retrospective analysis of 168 cases of EPTTCT for closure of small to medium tympanic membrane perforations from 2013-2023 was conducted.Patient sex,age range(pediatric vs adult),etiology of injury,success rate,complications,and postoperative hearing status were collected.RESULTS Graft uptake results indicated success in 94%of patients,with less than a 2%complication rate.Postoperative pure tone audiometry demonstrated hearing status improvement in 69%of patients.CONCLUSION EPTTCT has been shown to be effective in tympanic membrane perforation closures with minimal complications.This study further demonstrates the efficacy and safety of these procedures in a single-center review.

Nano“Undercover Agents”Lodge in Cartilage to Treat Osteoarthritis

The relentless pain and disability caused by osteoarthritis stem from the body’s own cartilage cells going rogue under inflammatory conditions.They secrete enzymes that devour the cushioning cartilage matrix,leading to joint damage.Conventional drugs cannot effectively reach this inflammatory source within the dense cartilage.

Functionalized Hydrogels for Articular Cartilage Tissue Engineering

Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.

Study on the Microstructure of Human Articular Cartilage/Bone Interface

For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope （SEM）, histological sections and MicroCT were used to observe, measure and model the micro- structure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified car- tilage and subchondral bone are in the manner of＂protrusion-pore＂ with average diameter of 17.0 gm and 34.1 lam respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

Repair of articular cartilage defects in minipigs by microfracture surgery and BMSCs transplantation

Objective:To investigate the feasibility of minimal invasive repair of cartilage defect by arthroscope-aided microfracture surgery and autologous transplantation of mesenchymal stem cells. Methods: Bone marrow of minipigs was taken out and the bone marrow derived mesenchymal stem cells (BMSCs) were isolated and cultured to passage 3. Then 6 minipigs were randomly divided into 2 groups with 6 knees in each group. After the articular cartilage defect was induced in each knee, the left defect received microfracture surgery and was injected with 2.5 ml BMSCs cells at a concentration of 3×107 cells/ml into the articular cavity; while right knee got single microfracture or served as blank control group. The animals were killed at 8 or 16 weeks, and the repair tissue was histologically and immunohistochemically examined for the presence of type Ⅱ collagen and glycosaminoglycans (GAGs) at 8 and 16 weeks. Results: Eight weeks after the surgery, the overlying articular surface of the cartilage defect showed normal color and integrated to adjacent cartilage. And 16 weeks after surgery, hyaline cartilage was observed at the repairing tissues and immunostaining indicated the diffuse presence of this type Ⅱ collagen and GAGs throughout the repair cartilage in the treated defects. Single microfracture group had the repairing of fibrocartilage, while during the treatment, the defects of blank group were covered with fewer fiber tissues, and no blood capillary growth or any immunological rejection was observed. Conclusion: Microfracture technique and BMSCs transplantation to repair cartilage defect is characterized with minimal invasion and easy operation, and it will greatly promote the regeneration repair of articular cartilage defect.

Thyroid Cartilage Chondrosarcoma Review: Management and Prognosis of a Rare Tumor

Objective: This article is a critical review of the literature concerning thyroid cartilage chondrosarcoma and is particularly focused on the management and prognosis of this rare entity. Study Design: A review of all the cases of thyroid cartilage chondrosarcoma reported in the literature up to January 2013. Methods: The search was carried out through the introduction of the MeSH terms: Chondrosarcoma, Laryngeal Cartilages, Thyroid Cartilage, Therapeutics. All the studies related to thyroid cartilage chondrosarcoma were selected together with a newly presented case. Results: A total of 47 cases have been described in the literature, and 35 of these include sufficient data for statistical analysis. The age of patients ranged from 40 to 77 years, with a male predilection (88.6%). The main symptoms were neck mass and hoarseness. Grade I and II tumors were most frequent. A total of 13 cases described an extension of the tumor beyond the thyroid cartilage. The most common treatment was partial laryngectomy (50%). All patients who died were male, with grade II or II-III tumor or associated sarcoma, had metastases and received radiotherapy in addition to total laryngectomy. Conclusion: Patient age and tumor size does not influence the prognosis. Tumor grade I and I-II have good prognoses, whereas the prognosis is unpredictable in tumors between grade II and III. Patients with associated sarcoma, or metastasis, have a worse prognosis. Partial laryngectomy is a good therapeutic option, although total laryngectomy is sometimes required in order to ensure complete resection.

Cartilage Wear in Healthy and Osteoarthritis Joints

This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant differences in their concentration. While examining the surface properties of OA joints, we found that OA PLs molecules cannot support lubrication, and increased friction was observed. Our lubrication mechanism was based on a surface active phospholipids (SAPL) multibilayer which in OA condition was deactivated and removed from the cartilage surface under OA conditions. Cartilage wettability study clearly demonstrated a significant decrease in hydrophobicity, the contact angle, θ (theta), dropping from 103° from bovine healthy cartilage to 65° in surface partially depleted and 35.1° for completely depleted surface. These results are discussed in the context that surface active phospholipid (SAPL) and lubricin, each has specific roles in a lamellar-repulsive lubrication system. However, deactivated phospholipid molecules are major indicator of cartilage wear (model) introduced in this study.

Advances in Negative Regulatory Mechanisms of Sox9 Gene Expression during Cartilage Development

As the main regulator of cartilage development, Sox9 gene can initiate transcription and expression of various enzymes and protein genes required for car- tilage growth and development. During this process, the expression and function of Sex9 are also regulated by a variety of factors and signaling pathways. More re- search is concerned about the positive regulation. At present, some studies dis- closed that negative regulation of Sox9 expression existed unique mechanisms. This study will discuss and summarize the negative regulatory mechanism of Sox9 gene by microRNA, NF-κB, Wnt, Notch and other factors and signaling pathways, in or- der to provide the basic framework for further investigating the expression and func- tion of Sox9 in cartilage development.

Use of bone morphogenetic proteins in mesenchymal stemcell stimulation of cartilage and bone repair

The extracellular matrix-associated bone morphogenetic proteins(BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-β protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell(MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted celltype lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair.

Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is as-sociated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechani-cal properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical pro-cedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morpho-logical features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells(MSCs) to be an appropriate cellular mate-rial for articular cartilage repair. These cells were origi-nally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic dif-ferentiation is an inherent property of MSCs noticedat the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative proper-ties. Moreover, these cells possess a considerable im-munomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening

AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage.METHODS Twenty-nine dogs were divided in two experimental groups: Group M-leg lengthening with manual distraction(1 mm/d in 4 steps), Group A-automated distraction(1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peronealand tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed.RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage(thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group.CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.

Injectable hydrogels for cartilage and bone tissue engineering

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix(ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed.

T1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis

AIM To investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.METHODS Magnetic resonance(MR) images were acquired from5 subjects scheduled for total knee arthroplasty(TKA)(mean age 70 years) and 20 young healthy control subjects without knee pain(mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained.Following TKA each condyle was divided into 4 parts(distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens(bone and cartilage blocks) were examined. For each joint,the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system.In magnetic resonance imaging(MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.RESULTS Eleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis(OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle, P = 0.461;medial posterior condyle(MPC), P = 0.352; lateral distal condyle, P = 0.654; lateral posterior condyle, P = 0.550],suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage.Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA(P= 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients. CONCLUSION Though cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.

Use of chondral fragments for one stage cartilage repair: A systematic review

AIM: To investigate the state of the art regarding Cartilage Autograft Implantation System(CAIS) or Particulated Juvenile Allograft Cartilage(PJAC).METHODS: The authors searched the English literature regarding CAIS and PJAC. The search strategy was:(particulated cartilage) OR autologous cartilage fragments. All basic science articles were included. Clinical articles with less than 10 patients treated and less than 6 mo of follow-up were excluded. With these criteria, a total of 17 articles were available for the present review. RESULTS: PJAC and CAIS are relatively novel techniques for cartilage repair. Good basic science evidence was described to support the concept. Although the preliminary clinical reports show encouraging results, clinical data are still limited, especially for CAIS. The indications for both techniques need to be precisely defined(age of the patients, size of the lesion, and involvement of the subchondral bone), together with other debated issues. CONCLUSION: In conclusion, the authors can state that encouraging preliminary results are available for both techniques. However, further studies are necessary to precisely determine the indications, surgical techniques, and long term outcomes for PJAC and CAIS.