What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis?

Chondroitin sulfate and glucosamine sulfate exert beneficial effects on the metabolism of in vitro models of cells derived from synovial joints: chondrocytes, synoviocytes and cells from subchondral bone, all of which are involved in osteoarthritis (OA). They increase type II collagen and proteoglycan synthesis in human articular chondrocytes and are able to reduce the production of some pro-inflammatory mediators and proteases, to reduce the cellular death process, and improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Clinical trials have reported a beneficial effect of chondroitin sulfate and glucosamine sulfate on pain and function. The structure-modifying effects of these compounds have been reported and analyzed in recent meta-analyses. The results for knee OA demonstrate a small but significant reduction in the rate of joint space narrowing. Chondroitin sulfate and glucosamine sulphate are recommended by several guidelines from international societies for the management of knee and hip OA, while others do not recommend these products or recommend only under condition. This comprehensive review clarifies the role of these compounds in the therapeutic arsenal for patients with knee OA.     

膝关节软骨损伤的研究进展

本文通过系统回顾分析中老年患者膝关节软骨损伤的流行病学特点、病因及可能的发病机制,进而探讨软骨损伤后的危害性,归纳外科治疗膝关节软骨损伤术式的选择及存在的优缺点,以及软骨损伤最新研究进展情况。     

Differential effect of hypoxia on human mesenchymal stem cell chondrogenesis and hypertrophy in hyaluronic acid hydrogels

Photocrosslinked hyaluronic acid (HA) hydrogels provide a conducive 3-D environment that supports the chondrogenesis of human mesenchymal stem cells (hMSCs). The HA macromer concentration in the hydrogels has a significant impact on the chondrogenesis of the encapsulated MSCs due to changes in the physical properties of the hydrogels. Meanwhile, hypoxia has been shown to promote MSC chondrogenesis and suppress subsequent hypertrophy. This study investigates the combinatorial effect of tuning HA macromer concentration (1.5–5% w/v) and hypoxia on MSC chondrogenesis and hypertrophy. To decouple the effect of HA concentration from that of crosslinking density, the HA hydrogel crosslinking density was adjusted by varying the extent of the reaction through the light exposure time while keeping the HA concentration constant (5% w/v at 5 or 15 min). It was found that hypoxia had no significant effect on the chondrogenesis and cartilaginous matrix synthesis of hMSCs under all hydrogel conditions. In contrast, the hypoxia-mediated positive or negative regulation of hMSC hypertrophy in HA hydrogels is dependent on the HA concentration but independent of the crosslinking density. Specifically, hypoxia significantly suppressed hMSC hypertrophy and neocartilage calcification in low HA concentration hydrogels, whereas hypoxia substantially enhanced hMSC hypertrophy, leading to elevated tissue calcification in high HA concentration hydrogels irrespective of their crosslinking density. In addition, at a constant high HA concentration, increasing hydrogel crosslinking density promoted hMSC hypertrophy and matrix calcification. To conclude, the findings from this study demonstrate that the effect of hypoxia on hMSC chondrogenesis and hypertrophy is differentially influenced by the encapsulating HA hydrogel properties.     

A biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin,hyaluronic acid and chondroitin sulfate

The development of hydrogels tailored for cartilage tissue engineering has been a research and clinical goal for over a decade. Directing cells towards a chondrogenic phenotype and promoting new matrix formation are significant challenges that must be overcome for the successful application of hydrogels in cartilage tissue therapies. Gelatin–methacrylamide (Gel-MA) hydrogels have shown promise for the repair of some tissues, but have not been extensively investigated for cartilage tissue engineering. We encapsulated human chondrocytes in Gel-MA-based hydrogels, and show that with the incorporation of small quantities of photocrosslinkable hyaluronic acid methacrylate (HA-MA), and to a lesser extent chondroitin sulfate methacrylate (CS-MA), chondrogenesis and mechanical properties can be enhanced. The addition of HA-MA to Gel-MA constructs resulted in more rounded cell morphologies, enhanced chondrogenesis as assessed by gene expression and immunofluorescence, and increased quantity and distribution of the newly synthesized extracellular matrix (ECM) throughout the construct. Consequently, while the compressive moduli of control Gel-MA constructs increased by 26 kPa after 8 weeks culture, constructs with HA-MA and CS-MA increased by 114 kPa. The enhanced chondrogenic differentiation, distribution of ECM, and improved mechanical properties make these materials potential candidates for cartilage tissue engineering applications.     

Self-crosslinked oxidized alginate/gelatin hydrogel as injectable,adhesive biomimetic scaffolds for cartilage regeneration

Biopolymeric hydrogels that mimic the properties of extracellular matrix have great potential in promoting cellular migration and proliferation for tissue regeneration. The authors reported earlier that rapidly gelling, biodegradable, injectable hydrogels can be prepared by self-crosslinking of periodate oxidized alginate and gelatin in the presence of borax, without using any toxic crosslinking agents. The present paper investigates the suitability of this hydrogel as a minimally invasive injectable, cell-attractive and adhesive scaffold for cartilage tissue engineering for the treatment of osteoarthritis. Time and frequency sweep rheology analysis confirmed gel formation within 20 s. The hydrogel integrated well with the cartilage tissue, with a burst pressure of 70 ± 3 mmHg, indicating its adhesive nature. Hydrogel induced negligible inflammatory and oxidative stress responses, a prerequisite for the management and treatment of osteoarthritis. Scanning electron microscopy images of primary murine chondrocytes encapsulated within the matrix revealed attachment of cells onto the hydrogel matrix. Chondrocytes demonstrated viability, proliferation and migration within the matrix, while maintaining their phenotype, as seen by expression of collagen type II and aggrecan, and functionality, as seen by enhanced glycosoaminoglycan (GAG) deposition with time. DNA content and GAG deposition of chondrocytes within the matrix can be tuned by incorporation of bioactive signaling molecules such as dexamethasone, chondroitin sulphate, platelet derived growth factor (PDGF-BB) and combination of these three agents. The results suggest that self-crosslinked oxidized alginate/gelatin hydrogel may be a promising injectable, cell-attracting adhesive matrix for neo-cartilage formation in the management and treatment of osteoarthritis.     

Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs

Hydrogels can provide a suitable environment for tissue formation by embedded cells, which makes them suitable for applications in regenerative medicine. However, hydrogels possess only limited mechanical strength, and must therefore be reinforced for applications in load-bearing conditions. In most approaches the reinforcing component and the hydrogel network have poor interactions and the synergetic effect of both materials on the mechanical properties is not effective. Therefore, in the present study, a thermoplastic polymer blend of poly(hydroxymethylglycolide-co-ε-caprolactone)/poly(ε-caprolactone) (pHMGCL/PCL) was functionalized with methacrylate groups (pMHMGCL/PCL) and covalently grafted to gelatin methacrylamide (gelMA) hydrogel through photopolymerization. The grafting resulted in an at least fivefold increase in interface-binding strength between the hydrogel and the thermoplastic polymer material. GelMA constructs were reinforced with three-dimensionally printed pHMGCL/PCL and pMHMGCL/PCL scaffolds and tested in a model for a focal articular cartilage defect. In this model, covalent bonds at the interface of the two materials resulted in constructs with an improved resistance to repeated axial and rotational forces. Moreover, chondrocytes embedded within the constructs were able to form cartilage-specific matrix both in vitro and in vivo. Thus, by grafting the interface of different materials, stronger hybrid cartilage constructs can be engineered.     

Costal cartilage fracture: A commonly missed thoracic injury in trauma patients

In this report, we describe a case of a 43-year-old male who sustained a displaced mid chondral costal cartilage fracture along with multiple ipsilateral rib fractures following a jet ski collision. Costal cartilage fractures (CC) are commonly missed on imaging evaluation, and accordingly underreported in the literature. High-energy blunt chest trauma represents the most common mechanism for CC injuries. Computed Tomography (CT) is the modality of choice to diagnose CC fractures along with the associated cardiopulmonary and abdominal injuries in polytrauma patients. There is currently no consensus with respect to the management of CC fractures. Further research is required to explore the long-term impact of CC fractures on thoracic cage stability.     

Ossicular chain reconstruction in chronic otitis media: hearing results and analysis of prognostic factors

IntroductionThe goal of ossiculoplasty is to improve hearing and the success of this procedure depends on several factors.ObjectiveAnalyze the hearing results in patients with chronic otitis media undergoing ossicular chain reconstruction, as well as predictive factors for successful surgery.MethodsCharts of patients undergoing ossiculoplasty between 2006 and 2016 were reviewed. Sixty-eight patients were included, totaling 72 ears. The following data was analyzed: gender, age, smoking status, laterality, pathology, audiometric exams, type of surgery, previous surgery, characteristics of the middle ear, otorrhea and ossicular chain status. Patients were also classified according to two indices: middle ear risk index and ossiculoplasty outcome parameter staging. The results were evaluated by comparing the air-bone gap before and after surgery. The success of reconstruction was defined as air-bone gap ≤20 dB and the improvement of speech reception Thresholds, calculated through the mean frequencies 0.5, 1, 2 and 3 kHz.ResultsReconstruction success rate was 61%. The mean preoperative air bone gap was 34.63 dB and decreased to 17.26 dB after surgery. There was a correlation between low risk in middle ear risk index and ossiculoplasty outcome parameter staging indices with postoperative success. The most frequently eroded ossicle was the incus and the type of prosthesis most used was tragal cartilage. In the patients without incus, we achieved success in 74.2% of the surgeries. In the absence of the stapes, the success rate decreased to 63.3%. In the absence of the malleus, 85% of the patients had and air bone gap ≤20 dB.ConclusionWe achieved good audiometric outcomes in ossiculoplasty and the results are comparable to other centers. Ossicle status influenced postoperative results, especially in the presence of stapes. We also concluded that the indexes analyzed may help to predict the success of the surgery.     

Endoscopic cartilage tympanoplasty: full thickness and partial thickness tragal graft

IntroductionCartilage is the grafting material of choice for certain disorders of the middle ear. The indications for its routine use remain controversial due to the possible detrimental effect on post-operative hearing.ObjectiveThe present study was carried out to report a personal experience with “tragal cartilage shield” tympanoplasty to compare the results, in terms of graft uptake and hearing improvement, of endoscopic cartilage shield technique using either partial thickness or full thickness tragal cartilage for type 1 tympanoplasty and to highlight the tips for single-handed endoscopic ear surgery.MethodsFifty patients with safe chronic suppurative otitis media, assisted at out-patient department from February 2014 to September 2015 were selected. They were randomly allocated into two groups, 25 patients were included in group A where a full thickness tragal cartilage was used and 25 patients included in group B where a partial thickness tragal cartilage was used. Audiometry was performed 2 months after the surgery in all cases and the patients were followed for one year.ResultsOut of the total of 50 patients 39 (78%) had a successful graft take up, amongst these 22 belonged to group A and 17 belonged to the group B. The hearing improvement was similar in both groups.ConclusionThis study reveals that endoscopic tragal cartilage shield tympanoplasty is a reliable technique; with a high degree of graft take and good hearing results, irrespective of the thickness. Furthermore, the tragal cartilage is easily accessible, adaptable, resistant to resorption and single-handed endoscopic ear surgery is minimally invasive, sutureless and provides a panoramic view of the middle ear.