The effect of the carbon fibres diameter on cell response

W ramach pracy otrzymano włókninę zbudowaną z włókien o różnych średnicach i wielkości, której mikrostruktura posiada biomimetyczny charakter, tzn. składa się z włókien o średnicach zbliżonych do średnic włókien występujących w tkankach. Badania biologiczne wykazały, że włókna o niskich średnicach są gorzej tolerowane przez tkanki.A three dimensional fibrous material, made from fibres differing in diameters and porosity, has been designed and prepared. These materials will constitute a 3D scaffold containing fibrous components mimicking the structure of natural tissue. The biological studies indicate that the fibres with bigger diameter allow for more intense and quick regeneration of surrounding tissue

In vitro and in vivo studies on biocompatibility of carbon fibres

In the present study we focused on the in vitro and in vivo evaluation of two types of carbon fibres (CFs): hydroxyapatite modified carbon fibres and porous carbon fibres. Porous CFs used as scaffold for tissues regeneration could simultaneously serve as a support for drug delivery or biologically active agents which would stimulate the tissue growth; while addition of nanohydroxyapatite to CFs precursor can modify their biological properties (such as bioactivity) without subsequent surface modifications, making the process cost and time effective. Presented results indicated that fibre modification with HAp promoted formation of apatite on the fibre surface during incubation in simulated body fluid. The materials biocompatibility was determined by culturing human osteoblast-like cells of the line MG 63 in contact with both types of CFs. Both tested materials gave good support to adhesion and growth of bone-derived cells. Materials were implanted into the skeletal rat muscle and a comparative analysis of tissue reaction to the presence of the two types of CFs was done. Activities of marker metabolic enzymes: cytochrome c oxidase (CCO) and acid phosphatase were examined to estimate the effect of implants on the metabolic state of surrounding tissues. Presented results evidence the biocompatibility of porous CFs and activity that stimulates the growth of connective tissues. In case of CFs modified with hydroxyapatite the time of inflammatory reaction was shorter than in case of traditional CFs

Long-term clinical and experimental/surface analytical studies of carbon/carbon maxillofacial implants

BACKGROUND:Over the past 30-40years, various carbon implant materials have become more interesting, because they are well accepted by the biological environment. The traditional carbon-based polymers give rise to many complications. The polymer complication may be eliminated through carbon fibres bound by pyrocarbon (carbon/carbon). The aim of this study is to present the long-term clinical results of carbon/carbon implants, and the results of the scanning electron microscope and energy dispersive spectrometer investigation of an implant retrieved from the human body after 8years.METHODS:Mandibular reconstruction (8-10years ago) was performed with pure (99.99%) carbon implants in 16 patients (10 malignant tumours, 4 large cystic lesions and 2 augmentative processes). The long-term effect of the human body on the carbon/carbon implant was investigated by comparing the structure, the surface morphology and the composition of an implant retrieved after 8years to a sterilized, but not implanted one.RESULTS:Of the 16 patients, the implants had to be removed earlier in 5 patients because of the defect that arose on the oral mucosa above the carbon plates. During the long-term follow-up, plate fracture, loosening of the screws, infection or inflammations around the carbon/carbon implants were not observed. The thickness of the carbon fibres constituting the implants did not change during the 8-year period, the surface of the implant retrieved was covered with a thin surface layer not present on the unimplanted implant. The composition of this layer is identical to the composition of the underlying carbon fibres. Residual soft tissue penetrating the bulk material between the carbon fibre bunches was found on the retrieved implant indicating the importance of the surface morphology in tissue growth and adhering implants.CONCLUSIONS:The surface morphology and the structure were not changed after 8years. The two main components of the implant retrieved from the human body are still carbon and oxygen, but the amount of oxygen is 3-4 times higher than on the surface of the reference implant, which can be attributed to the oxidative effect of the human body, consequently in the integration and biocompatibility of the implant. The clinical conclusion is that if the soft part cover is appropriate, the carbon implants are cosmetically and functionally more suitable than titanium plates

Doppler ultrasound in the measurement of pulse wave velocity: agreement with the Complior method

Aortic stiffness is an independent predictor factor for cardiovascular risk. Different methods for determining pulse wave velocity (PWV) are used, among which the most common are mechanical methods such as SphygmoCor or Complior, which require specific devices and are limited by technical difficulty in obtaining measurements. Doppler guided by 2D ultrasound is a good alternative to these methods. We studied 40 patients (29 male, aged 21 to 82 years) comparing the Complior method with Doppler. Agreement of both devices was high (R = 0.91, 0.84-0.95, 95% CI). The reproducibility analysis revealed no intra-nor interobserver differences. Based on these results, we conclude that Doppler ultrasound is a reliable and reproducible alternative to other established methods for the measurement of aortic PWV

Three-dimensional bio-printing and bone tissue engineering: technical innovations and potential applications in maxillofacial reconstructive surgery

Background Bone grafting has been considered the gold standard for hard tissue reconstructive surgery and is widely used for large mandibular defect reconstruction. However, the midface encompasses delicate structures that are surrounded by a complex bone architecture, which makes bone grafting using traditional methods very challenging. Three-dimensional (3D) bioprinting is a developing technology that is derived from the evolution of additive manufacturing. It enables precise development of a scaffold from different available biomaterials that mimic the shape, size, and dimension of a defect without relying only on the surgeon’s skills and capabilities, and subsequently, may enhance surgical outcomes and, in turn, patient satisfaction and quality of life. Review This review summarizes different biomaterial classes that can be used in 3D bioprinters as bioinks to fabricate bone scaffolds, including polymers, bioceramics, and composites. It also describes the advantages and limitations of the three currently used 3D bioprinting technologies: inkjet bioprinting, micro-extrusion, and laser-assisted bioprinting. Conclusions Although 3D bioprinting technology is still in its infancy and requires further development and optimization both in biomaterials and techniques, it offers great promise and potential for facial reconstruction with improved outcome

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

A tubular polycaprolactone/hyaluronic acid scaffolds for nasal cartilage tissue engineering

In this preliminary study, 3D nanofibrous porous scaffolds in the form of spiral tubes for future application as nasal cartilages implants were fabricated by combining polycaprolactone electrospun fibers with drug modified hyaluronic acid gel. It is expected that the spiral form of the scaffold with open geometries, large surface area, and distance between the scaffold walls will be helpful for improving future cell penetration into the scaffolds, nutrient transport and metabolic waste removal, which are otherwise limited in conventional electrospun tissue-engineered scaffolds. The tubular scaffolds structure, its porosity and fibers’ diameter were assessed via scanning electron microscopy, and biological properties of the scaffolds were evaluated in an in vitro study using Simulated Body Fluid (SBF). SEM results showed that apatite formed within a short period on tubular scaffolds after its immersion in SBF, demonstrating high in vitro bioactivity of the scaffolds

Włókniny węglowe modyfikowane kwasem hialuronowym jako potencjalne podłoża w leczeniu ubytków kostno-chrzęstnych

Damaged articular cartilage is known to have poor capacity for regeneration. Carbon fibres (CFs) have been widely investigated as cellular growth supports in cartilage tissue engineering. However, the long duration of the process of cartilage restoration limits the applicability of CFs implants in the treatment of cartilage tissue defects. Hyaluronic acid (HA) plays a key role in cartilage tissue development, repair and function. In the present study we focused on the in vitro and in vivo evaluation of two types of carbon nonwoven fabrics: HA modified and non-modified carbon nonwovens. The results of in vitro studies showed that cells attached well and retained their good viability in the carbon nonwoven matrix. The incorporation of hyaluronic acid resulted in the enhancement of cell proliferation. The results of in vivo studies showed a faster process of tissue regeneration in the case of HA modified carbon nonwovens. The results presented indicated that HA-modified carbon materials seem to be a suitable material for the treatment of osteochondral defects.Uszkodzona chrząstka stawowa posiada słabą zdolność do regeneracji. Od lat prowadzone są badania nad zastosowaniem włókien węglowych w inżynierii tkankowej chrząstki, jako podłoży podtrzymujących wzrost komórek. Niestety długi proces odbudowy chrząstki w obrębie implantu węglowego ogranicza możliwość zastosowania włóknin węglowych w leczeniu ubytków chrzęstnych. Kwas hialuronowy (HA) jest składnikiem chrząstki odpowiedzialnym za jej właściwy rozwój oraz proces regeneracji. Modyfikacja włóknin kwasem hialuronowym może w korzystny sposób wpłynąć na własności biologiczne implantów węglowych. W pracy przedstawiono wyniki badań in vitro oraz in vivo nad włókninami węglowymi modyfikowanymi kwasem hialuronowym oraz nad włókninami niemodyfikowanymi. Z przeprowadzonych badań in vitro wynika, że modyfikacja włóknin węglowych kwasem hialuronowym powoduje wzrost proliferacji komórek hodowanych na tych materiałach. Natomiast wyniki badań in vivo wykazały, że proces regeneracji tkanki następuje szybciej w przypadku włóknin węglowych modyfikowanych kwasem hialuronowym niż w przypadku włóknin niemodyfikowanych. Przeprowadzone badania wskazują, że włóknina węglowa modyfikowana kwasem hialuronowym może być rozważana jako potencjalny materiał w leczeniu ubytków kostno-chrzęstnych