Evidence-Based Approach to Orthobiologics for Osteoarthritis and Other Joint Disorders.

Osteoarthritis and cartilage lesions are a major cause of functional limitations which is why the goal of biological treatment is to preserve the native joint to delay the onset of OA. As a result of improvements in surgical techniques and technology, treatment options are more and more available, allowing the treatment of a whole range of injuries, from minor to extensive lesions both acute and chronic. In chondral lesion treatment, restoring hyaline-like cartilage provides improved durability of repaired tissue and desirable wear characteristics. Biological cell-based cartilage restoration treatment was developed to address the need for the long-term viability of repaired tissue. These procedures provide a reliable source of chondrocytes, whether directly or through the differentiation of multipotent precursor cells, capable of producing hyaline-like cartilage, with the minimal formation of fibrocartilage tissue. However, if arthritic changes begin biological therapies offer possibilities to delay. This chapter aims to discuss and give insights into these regenerative, joint preservation techniques for cartilage treatment and possible biological treatment in OA.

Is the Synovium the First Responder to Posttraumatic Knee Joint Stress? The Molecular Pathogenesis of Traumatic Cartilage Degeneration.

OBJECTIVE: The aim of this study was to evaluate if a similar catabolic and inflammatory gene pattern exists between the synovium, hyaline cartilage, and blood of patients with the knee joint tissues and if one precedes the other. DESIGN: A total of fifty-eight patients (34 females and 24 males) with a mean age of 44.7 years (range, 18-75) underwent elective knee arthroscopy due to previously diagnosed pathology. Full blood samples were collected preoperatively from synovium and cartilage samples intraoperatively. Real time PCR with spectrophotometric analysis was performed. Following genes taking part in ECM (extracellular matrix) remodeling were selected for analysis: MMP-1, MMP-2, MMP-8, MMP-9, MMP-13, MMP-14, ADAMTS-4 (Agg1) and ADAMTS-5 (Agg2) proteases, TIMP-1, and TIMP-2 - their inhibitors - and IL-1 and TNF-α cytokines. RESULTS: Analysis revealed a strong and significant correlation between gene expression in synovial and systemic blood cells (p <0.05 for all studied genes) with ADAMTS-4, ADAMTS-5, IL-1, TNF-α and TIMP-2 expression most positively correlated with an R>0.8 for each. An analysis between chondrocytes and systemic blood gene expression shown no significant correlation for all genes. Bivariate correlation of International Cartilage Repair Society grading and genes expression revealed significant associations with synovial MMP-1, MMP-2, MMP-8, MMP-9, IL-1, TNF-α and TIMP-2. CONCLUSION: We suggest that the synovial tissue is the first responder for knee joint stress factors in correlation with the response of blood cells. The chondrocyte's genetic response must be further investigated to elucidate the genetic program of synovial joints, as an organ, during OA development and progression.

Assessment of the influence of vegetarian diet on the occurrence of erosive and abrasive cavities in hard tooth tissues.

INTRODUCTION: The aim of the study was to determine the potential relation between vegetarian diet and tooth erosion and abrasion. MATERIAL/METHODS: The examination included 46 vegetarians and the same number in the control group. Clinical research was carried out in order to detect the presence of abrasive and erosive changes and the level of hygiene in oral cavities. The questionnaire survey concerned dietary and hygienic habits. Statistical analysis of the data was conducted with Chi-square test and Mann-Whitney U test. The relations between following a vegetarian diet and the occurrence of non-carious cavities was tested with models of logistic regression. RESULTS: Tooth erosion was present among 39.1% of vegetarians and 23.9% of controls, while abrasion appeared among 26.1% and 10.9%, respectively, and the differences were statistically insignificant. The distribution of the changes was similar in both groups. Among vegetarians, significantly more frequent consumption of sour products (predominantly raw vegetables and fruit and tomatoes) was observed. The level of oral hygiene and hygienic habits were similar in both groups. The analysis of statistical regression did not reveal any relations between following a vegetarian diet and the occurrence of tooth erosion and abrasion. DISCUSSION: The results did not reveal any direct influence of vegetarian diet on the occurrence of erosive and abrasive changes. However, in the vegetarian group, more frequent consumption of some sour products and more commonly used horizontal brushing method were observed, with a slightly higher occurrence of non-carious cavities. Further research is required to obtain unambiguous conclusions.

Single-molecule force spectroscopy reveals structural differences of heparan sulfate chains during binding to vitronectin.

The syndecans represent an ongoing research field focused on their regulatory roles in normal and pathological conditions. The role of syndecans in cancer progression is well documented, implicating their importance in diagnosis and even proposing various potential cancer treatments. Thus, the characterization of the unbinding properties at the single-molecule level will appeal to their use as targets for therapeutics. In our study, syndecan-1 and syndecan-4 were measured during the interaction with the vitronectin HEP II binding site. Our findings show that syndecans are calcium ion dependent molecules that reveal distinct, unbinding properties indicating the alterations in the structure of heparan sulfate (HS) chains, possibly in the chain sequence or sulfation pattern. In this way, we suppose that HS chain affinity to extracellular matrix proteins may govern cancer invasion by altering the syndecans' ability to interact with cancer-related receptors present in the tumor microenvironment, thereby promoting the activation of various signaling cascades regulating tumor cell behavior.

In Vitro Assessment of Long-Term Fluoride Ion Release from Nanofluorapatite.

The issue concerning the tooth decay is ongoing, therefore the study of materials with potential use in its prevention is crucial. This study aimed to analyze the long-term release of fluoride from synthesized nanofluorapatite in various in vitro environments for its potential use in dental materials. We placed 100 mg samples in 0.9% NaCl or deionized water and incubated them at 37 °C or 22 °C for 12 weeks. F- levels were read at 1, 3, 24, 48, 72, and 96 h, and thereafter weekly. The levels of F- released at specific time intervals, as well as their cumulative values were compared. In a solution of 0.9% NaCl at 22 °C, there were no significant differences in the amount of F- released in the assessed time intervals, while at 37 °C, the highest value was read after 24 h (0.0697 ppm + 0.0006; p < 0.05). In deionized water, the highest amount of F- at 22 °C was read after 4 weeks (0.0776 ppm + 0.0028; p < 0.05), and at 37 °C, it was also the highest after 4 weeks (0.0910 ppm + 0.0156; p < 0.05). Under the same conditions, after 5 weeks the cumulative level of F- released (0.6216 ppm + 0.0085) significantly increased (p < 0.05), when compared to the samples placed in 0.9% NaCl at 37 °C and 22 °C (0.5493 ppm + 0.0321 and 0.5376 ppm + 0.0234, respectively). FAp releases F- for a long period of time in all assessed environments, therefore it is advised to continue testing in vivo models. Due to the probable remineralization effect towards hard tooth tissues, fluorapatite can be used in the prevention and treatment of dental caries and dentin hypersensitivity.

Probing the recognition specificity of αVß1 integrin and syndecan-4 using force spectroscopy.

The knowledge on how cells interact with microenvironment is particularly important in understanding the interaction of cancer cells with surrounding stroma, which affects cell migration, adhesion, and metastasis. The main cell surface receptors responsible for the interaction with extracellular matrix (ECM) are integrins, however, they are not the only ones. Integrins are accompanied to other molecules such as syndecans. The role of the latter has not yet been fully established. In our study, we would like to answer the question of whether integrins and syndecans, possessing similar functions, share also similar unbinding properties. By using single molecule force spectroscopy (SMFS), we conducted measurements of the unbinding properties of αVß1 and syndecan-4 in the interaction with vitronectin (VN), which, as each ECM protein, possesses two binding sites specific to integrins and syndecans. The unbinding force and the kinetic off rate constant derived from SMFS describe the stability of single molecular complex. Obtained data show one barrier transition for each complex. The proposed model shows that the unbinding of αVß1 from VN proceeds before the unbinding of SDC-4. However, despite different unbinding kinetics, the access to both receptors is needed for cell growth and proliferation.

How Complex Is the Concanavalin A-Carboxypeptidase Y Interaction?

Lectin-carbohydrate interactions can be exploited in ultrasensitive biochemical recognition or medical diagnosis. For this purpose, besides the high specificity of the interactions, an appropriate methodology for their quantitative and detailed characterization is demanded. In this work, we determine the unbinding properties of the concanavalin A-carboxypeptidase Y complex, which is important for characterization of glycoproteins on the surface of biological cells. To achieve the goal, we have developed a methodology based on dynamic force spectroscopy measurements and two advanced theoretical models of force-induced unbinding. Our final results allowed excluding both, rebinding processes and the multibarrier character of the interaction potential, as possible explanations of the concanavalin A-carboxypeptidase Y unbinding mechanisms. Such characteristics as the position and height of the activation barrier and the force-free dissociation rate were determined. We hope our paper contributes to a better understanding of the unbinding processes in receptor-ligand complexes.

Primary Anterior Cruciate Ligament Repair With Hyaluronic Scaffold and Autogenous Bone Marrow Aspirate Augmentation in Adolescents With Open Physes.

It is well known that the anterior cruciate ligament (ACL) is the main stabilizer to the anterior tibial translation in the knee. The current gold standard of treatment for such lesions is ACL reconstruction. However, there are notable disadvantages to ACL reconstruction that include loss of proprioception, donor site morbidity, incomplete return to high-demand sports, and the inability to restore normal kinematics of the knee joint. Additionally, in adolescents who have open physes, there is a risk of potential iatrogenic growth plate injury. Tibial-sided soft-tissue avulsion is a rare subtype of ACL injuries. This Technical Note presents a method for primary anatomic ACL repair with a bioabsorbable scaffold and bone marrow concentrate augmentation for an acute distal ACL injury. Our technique is an alternative to reconstruction as it allows the preservation of the native insertion site and has the potential to reduce the risk of posttraumatic osteoarthritis.

Lateral Extra-articular Tenodesis with Iliotibial Band Strip - a Solution for Anterolateral Instability?

It is widely acknowledged that anterior cruciate ligament (ACL) injury is the cause of anterolateral insta-bility, but in some cases not only the ACL ruptures, but also anterolateral structures (ALS), including the antero-lateral ligament. Their insufficiency may be the cause of residual instability after ACL reconstruction, which significantly increases the risk of graft rupture. In the past, anterolateral instability caused by ACL injury was treat-ed with extra-articular reconstructions, including lateral extra-articular tenodesis. Nowadays those techni-ques are used simultaneously in cases of complex anterolateral and rotational instability. This article briefly describes historical methods of lateral tenodesis and presents step-by-step two techniques used in our depart-ments involving two alternative graft femoral fixation methods.

Co-expression of the aryl hydrocarbon receptor and estrogen receptor in the developing teeth of rat offspring after rat mothers' exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and the protective action of α-tocopherol and acetylsalicylic acid.

BACKGROUND: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can cause adverse effects in many organs. Toxic effects are caused due to the formation of a TCDD complex with the cytoplasmatic aryl hydrocarbon receptor (AhR), whose mechanism of action is similar to that of the estrogen receptor (ER). Some substances, including α-tocopherol (E) and acetylsalicylic acid (ASA), can reduce the toxic effects of TCDD in offspring. OBJECTIVES: The objective of this study was to evaluate the co-expression of AhR and ER in the incisors of rat offspring whose mothers were exposed to TCDD, using immunohistochemical and histological techniques. Moreover, the possible protective role of E and ASA was investigated. MATERIAL AND METHODS: Four groups of 2-day-old rat offspring, whose mothers were intoxicated by TCDD before mating, were established: control group (C), TCDD group, TCDD+E group and TCDD+ASA group. RESULTS: In the TCDD group, there was an increase in ER expression and a decrease in AhR expression in comparison with the C group. In the TCDD+E and TCDD+ASA groups, there was a weak or negative ER expression and slightly stronger expression of AhR than in the TCDD group. CONCLUSIONS: The co-expression of AhR and ER during tooth development suggests the role of AhR and ER in the control of this process. Both receptors are also involved in the process of detoxification of TCDD. The increase in AhR in TCDD+E and TCDD+ASA groups indicate a preventive action of antioxidant and antiinflammatory pharmaceutics, which may limit negative effects of TCDD.

Unbinding Kinetics of Syndecans by Single-Molecule Force Spectroscopy.

Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. Despite structural similarities between all members of the syndecan family, their specific attachment to extracellular matrix proteins is defined by heparan and chondroitin chains. We postulate various unbinding kinetics for each type of single syndecan complex. Force spectroscopy data, recorded by atomic force microscope, were analyzed using two theoretical approaches describing force-induced unbinding, authored by Bell-Evans and Dudko-Hummer-Szabo. Our results reveal distinct unbinding pathways dependent on the syndecan family member. Syndecan-1 unbinds by passing over two energy barriers, inner and outer. Syndecan-4 unbinds by crossing over only one energy barrier. It has already been reported that both syndecans bear heparan chains that are structurally indistinguishable. Our finding reveals that unbinding of single syndecan complexes is family-member-dependent. Distinct unbinding pathways can be attributed to structural differences of heparan and chondroitin chains.

Oral cavity health among cystic fibrosis patients: Literature overview.

Cystic fibrosis is a genetic disorder in which the mutation of the Cystis Fibrosis Transmembrane Conductance Regulator (CFTR) gene that codes the protein forming a chloride channel of epithelial cells results in its distorted functioning. The manifestations of the disorder are mainly observed in the respiratory and digestive system. Accumulation of sticky and thick mucus is the dominant clinical symptom; it leads to chronic infections and gradual tissue destruction. Although cystic fibrosis remains incurable, it is currently feasible to extend patients' life expectancy thanks to modern therapy possibilities. As cystic fibrosis is no longer the domain of pediatricians, health care to CF patients needs to be provided by doctors of various specializations. The multidisciplinary team of doctors should include a dentist aware of specific prevention and treatment needs of this group of patients. It results from the fact that in the course of cystic fibrosis it is possible to observe a variety of changes in the oral cavity environment. The study presents dental issues observed in CF patients and reported in literature. Particular attention was paid to dental caries, mineralization disorders of hard dental tissues, gingivitis and the change in the content and properties of saliva; moreover, prevention and treatment options regarding oral cavity health is this group of patients were taken into consideration.

Long-term release of fluoride from fissure sealants-In vitro study.

The intensity of the cariostatic activity of fluoride ions can be attributed to their multidirectional influence on the caries process. They are an irreplaceable factor that helps sustain mineral balance of dental tissues, simultaneously demonstrating antibacterial properties. As a consequence, many manufacturers of fissure sealants include fluoride ions in their products. The aim of this in vitro study was to determine long-term fluoride release from four fissure sealants (Conseal F, Fissurit FX, Delton Fs+, Admira Seal). During a 14-week-long observation, all the materials showed a relatively constant level of F- release; however, it is crucial to mention that within the first 48h, the most significant increase in fluoride release was found for Fissurit and Delton sealants. Based on the overall assessment, the highest total amount of the released fluoride ions was observed for Delton, and the lowest level was reported for Admira Seal.

Assessment of Heat Hazard during the Polymerization of Selected Light-Sensitive Dental Materials.

Introduction. Polymerization of light-cured dental materials used for restoration of hard tooth tissue may lead to an increase in temperature that may have negative consequence for pulp vitality. Aim. The aim of this study was to determine maximum temperatures reached during the polymerization of selected dental materials, as well as the time that is needed for samples of sizes similar to those used in clinical practice to reach these temperatures. Materials and Methods. The study involved four composite restorative materials, one lining material and a dentine bonding agent. The polymerization was conducted with the use of a diode light-curing unit. The measurements of the external surface temperature of the samples were carried out using the Thermovision®550 thermal camera. Results. The examined materials significantly differed in terms of the maximum temperatures values they reached, as well as the time required for reaching the temperatures. A statistically significant positive correlation of the maximum temperature and the sample weight was observed. Conclusions. In clinical practice, it is crucial to bear in mind the risk of thermal damage involved in the application of light-cured materials. It can be reduced by using thin increments of composite materials.

Celiac disease and its impact on the oral health status - review of the literature.

The paper presents the most recent reports on celiac disease, especially its manifestations within the oral cavity. Particular attention should be paid to typical dental enamel defects with a various degree of advancement: discolorations, horizontal groves and pits, and even significant structural destruction causing the change of the dental crown. Symmetric location of defects within all dentition sections, and within the same anatomic groups of teeth (the most frequently: incisors and first permanent molars), is specific for celiac disease. The changes described above may be the only manifestation of celiac disease; therefore, in the case of their occurrence further studies towards gluten intolerance are recommended even when other symptoms are not present. In celiac patients, recurrent aphthae and other disorders of the oral mucosa such as ulceration, erythema, atrophic glossitis, as well as dryness and a burning sensation (particularly of the tongue) may be present, which may be caused by malnutrition. Delayed tooth eruption may also be a consequence of alimentary deficiency in celiac disease.