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.

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.

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.

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.

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.

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.

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.

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.

The role of TGF-beta3 in cartilage development and osteoarthritis

Articular cartilage serves as a low-friction,load-bearing tissue without the support with blood vessels,lymphatics and nerves,making its repair a big challenge.Transforming growth factor-beta 3(TGF-β3),a vital member of the highly conserved TGF-βsuperfamily,plays a versatile role in cartilage physiology and pathology.TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses,including cell survival,proliferation,migration,and differentiation.Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy,its regulatory role is especially important to cartilage development.Increased TGF-β3 plays a dual role:in healthy tissues,it can facilitate chondrocyte viability,but in osteoarthritic chondrocytes,it can accelerate the progression of disease.Recently,TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis(OA)owing to its protective effect,which it confers by enhancing the recruitment of autologous mesenchymal stem cells(MSCs)to damaged cartilage.However,the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood.In this review,we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology,providing up-to-date strategies for cartilage repair and preventive treatment.

Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression

Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.

Robotic in situ bioprinting for cartilage tissue engineering

Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for efficacious cartilage repair,and long-term patient outcomes are not satisfying.Three-dimensional bioprinting has been used to fabricate biochemical and biophysical environments that aim to recapitulate the native microenvironment and promote tissue regeneration.However,conventional in vitro bioprinting has limitations due to the challenges associated with the fabrication and implantation of bioprinted constructs and their integration with the native cartilage tissue.In situ bioprinting is a novel strategy to directly deliver bioinks to the desired anatomical site and has the potential to overcome major shortcomings associated with conventional bioprinting.In this review,we focus on the new frontier of robotic-assisted in situ bioprinting surgical systems for cartilage regeneration.We outline existing clinical approaches and the utilization of robotic-assisted surgical systems.Handheld and robotic-assisted in situ bioprinting techniques including minimally invasive and non-invasive approaches are defined and presented.Finally,we discuss the challenges and potential future perspectives of in situ bioprinting for cartilage applications.

Divergent chondro/osteogenic transduction laws of fibrocartilage stem cell drive temporomandibular joint osteoarthritis in growing mice

The anterior disc displacement(ADD)leads to temporomandibular joint osteoarthritis(TMJOA)and mandibular growth retardation in adolescents.To investigate the potential functional role of fibrocartilage stem cells(FCSCs)during the process,a surgical ADDTMJOA mouse model was established.From 1 week after model generation,ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis(OA)-like joint cartilage degeneration,manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis.Lineage tracing using Gli1^(-)CreER^(+);Tm^(fl/-)mice and Sox9-CreER^(+);Tm^(fl/-)mice showed that ADD interfered with the chondrogenic capacity of Gli1+FCSCs as well as osteogenic differentiation of Sox9+lineage,mainly in the middle zone of TMJ cartilage.Then,a surgically induced disc reposition(DR)mouse model was generated.The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice.And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment.In conclusion,ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage,resulting in cartilage degeneration and loss of subchondral bone homeostasis,finally causing TMJ growth retardation.DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.

3D printing of personalized polylactic acid scaffold laden with GelMA/autologous auricle cartilage to promote ear reconstruction

At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.

Purifi cation and identification of anti-inflammatory peptides from sturgeon (Acipenser schrenckii) cartilage

Cartilage is a nonedible byproduct with little saleable value.However,previous studies have proposed the possibility of producing peptides from cartilage with immune function modulation potential.The current study aimed to investigate the potential anti-inflammatory activity of peptides derived from sturgeon(Acipenser schrenckii)cartilage in lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.Five peptide sequences,including four novel peptides,were identified from ethanol-soluble cartilage hydrolysates.Among these five peptides,LTGP,LLLE,LLEL and VGPAGPAGP reduced the production of nitric oxide(NO)and interleukin-6(IL-6)while increasing interleukin-10(IL-10)excretion.Transcriptome analysis suggested the inhibition of activated mitogen-activated protein kinase(MAPK)and interleukin-17(IL-17)signaling pathways after LLEL intervention.MAPK,which is involved in the IL-17 signaling pathway,was further proved to be blocked by downregulating the phosphorylation of p38,extracellular-signal regulated protein kinase(ERK),and c-jun N-terminal kinase(JNK).This novel peptide offers an attractive approach to develop functional foods.

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.

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.

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.

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.