Genetic expression of Col-2A and Col-10A as a function of administration of IGF-1 &TGF-<i>β</i>with and without anterior mandibular repositioning appliance on the growth of mandibular condylar cartilage in young rabbit

New Zealand (NZ) young rabbits with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) with and without mandibular anterior repositioning appliances are explored for the growth of the mandibular condylar cartilage (MCC). 32 growing NZ and rabbits were divided into 4 groups: the group with saline injection in TMJ, the group which received growth factor injection in TMJ, the group which received anterior positioning appliance and the group which received growth factors injection as well as mandibular repositioning appliance. Gene expression was studied by real-time RT-PCR and cartilage growth by histomorphometry. Administration of growth factors along with mandibular repositioning appliances has induced 1) 1.70-fold expression of Col-2Agene (p value < 0.0005) and 2) 1.47-fold expression of Col-10Agene (p value < 0.0005). In contrast, administration of only mandibular repositioning appliances induced 1) 1.28-fold expression of Col-2Agene (p value < 0.0005) and 2) merely 0.62-fold expression of Col-10Agene (p value < 0.0005), while administration of growth factors only induced 1) mere 0.56-fold expression of Col-2Agene (p value 10A gene (p value growth factors along with mandibular repositioning appliances causes an increase in genetic expressions which have been corroborated by histomorphometry and validated by statistical analysis, during an accelerated growth of mandibular condylar cartilage. Administration of growth factors in the TMJ could provide a synergistic role along with mandibular repositioning appliances for treatment of mandibular retrognathism as well as disorders on the MCC.

Elevated levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and vascular endothelial growth factor in patients with knee articular cartilage injury

BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.

Cartilage repair techniques of the talus: An update

Symptomatic chondral or osteochondral defects of the talus reduce the quality of life of many patients.Although their pathomechanism is well understood,it is well known that different aetiologic factors play a role in their origin.Additionally,it is well recognised that the talar articular cartilage strongly differs from that in the knee.Despite this fact,many recommendations for the management of talar cartilage defects are based on approaches that were developed for the knee.Conservative treatment seems to work best in paediatric and adolescent patients with osteochondritis dissecans.However,depending on the size of the lesions,surgical approaches are necessary to treat many of these defects.Bone marrow stimulation techniques may achieve good results in small lesions.Large lesions may be treated by open procedures such as osteochondral autograft transfer or allograft transplantation.Autologous chondrocyte transplantation,as a restorative procedure,is well investigated in the knee and has been applied in the talus with increasing popularity and promising results but the evidence to date is poor.The goals of the current article are to summarise the different options for treating chondral and osteochondral defects of the talus and review the available literature.

Non-invasive MRI assessment of the articular cartilage in clinical studies and experimental settings

Attrition and eventual loss of articular cartilage are important elements in the pathophysiology of osteoarthritis(OA).Preventing the breakdown of cartilage is believed to be critical to preserve the functional integrity of a joint.Chondral injuries are also common in the knee joint,and many patients benefit from cartilage repair.Magnetic resonance imaging(MRI) and advanced digital post-processing techniques have opened possibilities for in vivo analysis of cartilage morphology,structure,and function in healthy and diseased knee joints.Techniques of semi-quantitative scoring of human knee cartilage pathology and quantitative assessment of human cartilage have been developed.Cartilage thickness and volume have been quantified in humans as well as in small animals.MRI detected cartilage loss has been shown to be more sensitive than radiographs detecting joint space narrowing.It is possible to longitudinally study knee cartilage morphology with enough accuracy to follow the disease-caused changes and also evaluate the therapeutic effects of chondro-protective drugs.There are also several MRI methods that may allow evaluation of the glycosaminoglycan matrix or collagen network of articular car-tilage,and may be more sensitive for the detection of early changes.The clinical relevance of these methods is being validated.With the development of new therapies for OA and cartilage injury,MR images will play an important role in the diagnosis,staging,and evaluation of the effectiveness of these therapies.

Update on mesenchymal stem cell therapies for cartilage disorders

Cartilage disorders, including focal cartilage lesions, are among the most common clinical problems in orthopedic practice. Left untreated, large focal lesions may result in progression to osteoarthritis, with tremendous impact on the quality of life of affected individuals. Current management strategies have shown only a modest degree of success, while several upcoming interventions signify better outcomes in the future. Among these, stem cell therapies have been suggested as a promising new era for cartilage disorders. Certain characteristics of the stem cells, such as their potential to differentiate but also to support healing made them a fruitful candidate for lesions in cartilage, a tissue with poor healing capacity. The aim of this editorial is to provide an update on the recent advancements in the field of stem cell therapy for the management of focal cartilage defects. Our goal is to present recent basic science advances and to present the potential of the use of stem cells in novel clinical interventions towards enhancement of the treatment armamentarium for cartilage lesions. Furthermore, we highlight some thoughts for the future of cartilage regeneration and repair and to explore future perspectives for the next steps in the field.

Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus

Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.

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.

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.

Research Progress of Osteochondral Composite Scaffolds in Tissue Engineering Cartilage Repair

Repair and regeneration of articular cartilage has always been a major challenge in the medical field due to its peculiar structure(e.g.sparsely distributed chondrocytes,no blood supply).Cartilage tissue engineering is one promising strategy for cartilage repair,however,one critical issue for cartilage tissue engineering is the integration between tissue-engineered and native cartilage.In recent years,osteochondral tissue engineering has attracted growing interest for overcoming this problem.Herein,we review the development of osteochondral tissue engineering.Firstly,currently used seed cells in osteochondral tissue engineering will be described.Secondly,several types of scaffolds and their(dis)advantage for osteochondral tissue engineering will be introduced.Thirdly,the growth factors currently used in osteochondral tissue engineering will be presented and discussed.

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.

New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness.We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials,and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures.Adult articular cartilage has low capacity to repair itself,and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, result-ing in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubM ed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the wellknown tissue engineering methods for the treatment of knee osteoarthritis.

Effect of osteoporosis and intervertebral disc degeneration on endplate cartilage injury in rats

Objective:To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.Methods:A total of 48 female Sprague Dawley rats(3 months)were randomly divided into Groups A,B,C and D with 12 rats in each group.Osteoporosis and intervertebral disc degeneration composite model,simple degeneration model and simple osteoporosis model were prepared in Groups A,B and C respectively.After modeling,four rats of each group at 12th.18th and 24th week were sacrificed,Intervertebral height of cervical vertebra C6/C7 was measured.Micro-CT was used to image the endplate of cephalic and caudal cartilage at C6/C7 intervertebral disc.Abraded area rate of C6 caudal and C7 cephalic cartilage endplate was calculated,and then C6/C7 intervertebral disc was routinely embedded and sectioned.stained with safranin O to observe histological changes microscopically.Results:At 12,18 and24 weeks,intervertebral disc height of C6/C7 were(0.58±0.09)mm,(0.53±0.04)mm and(0.04±0.06)mm in Group A rats,(0.55±0.05)mm,(0.52±0.07)mm and(0.07±0.05)mm in Group B rats.At 24th week.intervertebral disc height of Group A rats was significantly lower than that of Group B rats(P<0.05);intervertebral disc height of Groups A and B rats at each time point were significantly lower than that of Groups C and D(P<0.05).There was no significantly statistical difference of intervertebral disc height between Groups C and D(P>0.05).At 12 and 18 weeks,the abraded rate of C6 caudal and C7 cephalic cartilage endplate in Group A rats were significantly higher than that in Groups B.C and D rats(P<0.05);the abraded rate in Group B was significantly higher than that in Groups C and D(P>0.05).Microscopic observation of CT showed that ventral defects in C6caudal or C7 cephalic cartilage endplate in Groups A and B appeared after 12 weeks of modeling;obvious cracks were found in front of the C6 and C7 vertebral body,and cartilage defect shown the trend of"repairing"at 18 and 24 weeks after modeling.Conclusions:Intervertebral disc degeneration and osteoporosis can cause damage to the cartilage endplate.Co-existence of these two factors can induce more serious damage to the endplate.which has possitive correlation with intervertebral disc degeneration.Osteoporosis plays a certain role in intervertebral disc degeneration process,and accelerates the degeneration of intervertebral disc in a specific time window.

Mesenchymal stem cells for cartilage regeneration in dogs

Articular cartilage damage and osteoarthritis (OA) are common orthopedic diseases in both humans and dogs. Once damaged, the articular cartilage seldom undergoes spontaneous repair because of its avascular, aneural, and alymphatic state, and the damage progresses to a chronic and painful situation. Dogs have distinctive characteristics compared to other laboratory animal species in that they share an OA pathology with humans. Dogs can also require treatment for naturally developed OA;therefore, effective treatment methods for OA are desired in veterinary medicine as well as in human medicine. Recently, interest has grown in regenerative medicine that includes the use of mesenchymal stem cells (MSCs). In cartilage repair, MSCs are a promising therapeutic tool due to their self-renewal capacity, ability to differentiate into cartilage, potential for trophic factor production, and capacity for immunomodulation. The MSCs from dogs (canine MSCs;cMSCs) share various characteristics with MSCs from other animal species, but they show some deviations, particularly in their differentiation ability and surface epitope expression. In vivo studies of cMSCs have demonstrated that intraarticular cMSC injection into cartilage lesions results in excellent hyaline cartilage regeneration. In clinical situations, cMSCs have shown great therapeutic effects, including amelioration of pain and lameness in dogs suffering from OA. However, some issues remain, such as a lack of regulations or guidelines and a need for unified methods for the use of cMSCs. This review summarizes what is known about cMSCs, including their in vitro characteristics, their therapeutic effects in cartilage lesion treatment in preclinical in vivo studies, their clinical efficacy for treatment of naturally developed OA in dogs, and the current limitations of cMSC studies.

Poly(<i>N</i>-isopropylacrylamide-co-<i>N</i>-<i>tert</i>-butylacrylamide)- grafted hyaluronan as an injectable and self-assembling scaffold for cartilage tissue engineering

Novel poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-grafted hyaluronan [P(NIPAAm-co-NtBAAm)-g-HA] has been developed as a modified derivative to improve phase-transition characteristics of PNIPAAm-g-HA, which has a lower critical solution temperature (LCST) of approximately 32°C. This promising self-assembling biomaterial has potential as an injectable scaffold for in situ cartilage tissue engineering. LCST of the P(NIPAAm-co-NtBAAm)-g-HA decreased to approximately 3.6°C compared to that of the original PNIPAAm-g-HA. This modification enabled self-assembly at body temperatures lower than the temperature of the parental PNIPAAm-g-HA molecule. Cytotoxicity and acute systemic toxicity assays revealed that P(NIPAAm-co-NtBAAm)-g-HA was not hazardous. The DNA content of chondrogenic differentiated mesenchymal stem/stromal cells (MSCs) embedded in the gels was higher than that of biomaterial-free aggregates during the culture periods. Cartilage-related genes were also expressed in chondrogenic differentiated MSCs embedded in the P (NIPAAm-co-NtBAAm)-g-HA hydrogel. Specifically, an increased expression of SRY-related HMG box-containing gene 9 (Sox9) observed in the hydrogel group compared to controls. These data suggest that P(NIPAAm-co-NtBAAm)-g-HA is a promising injectable scaffold with thermoresponsive properties suitable for in situ cartilage tissue engineering.

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.

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.

Repair effect of articular cartilage defects by nitric oxide synthase inhibitor

Objective To discuss repairing effects of articular cartilage defects by nitric oxide synthase inhibitor (S methylisothiourea, SMT), and explore the role of nitric oxide in cartilage repair. Methods Full-thickness defects of cartilage were created in the intercondylar trochlear groove of femur of thirty-six adult New Zealand white rabbits, and were divided into three gorups. Twenty-four defects were untreated as the control, twenty-four were filled with fibrin glue and impregnated with rhBMP AS rhBMP group, the rest twenty-four were filled with fibrin glue and impregnated with rhBMP, and hypodermic injection with SMT as SMT group. The animals were sacrified at sixteen weeks postoperatively, and the gross appearance of the defect was estimated. The repair tissue was examined histologically and was evaluated according to the grading scale of histology. The amount of released NO and the activities of nitric oxide synthase(NOS) were examined by chemical colorimetry. The distribution of type-Ⅰ , Ⅱ

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.

Mesenchymal stem cells for cartilage regeneration in osteoarthritis

Osteoarthritis(OA) is a slowly progressive disease where cartilage of the synovial joint degenerates. It is most common in the elderly where patients experience pain and reduce physical activity. In combination with lack of conventional treatment, patients are often left with no other choices than arthroplasty. Over the last years, multipotent stromal cells have been used in efforts to treat OA. Mesenchymal stem/progenitor cells(MSCs) are stromal cells that can differentiate into bone, fat, and cartilage cells. They reside within bone marrow and fat. MSCs can also be found in synovial joints where they affect the progression of OA. They can be isolated and proliferated in an incubator before being applied in clinical trials. When it comes to treatment, emphasis has hitherto been on autologous MSCs, but allogenic cells from healthy donors are emerging as another source of the cells. The first adaptations of MSCs revolved in the use of cellrich matrix, delivered as invasive surgical procedure, which resulted in production of hyaline cartilage and fibrocartilage. However, the demand for less invasive delivery of cells has prompted the use of direct intraarticular injections, wherein a large amount of suspended cells are implanted in the cartilage defect.