Osteointegration of soft tissue grafts within the bone tunnels in anterior cruciate ligament reconstruction can be enhanced

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice. © 2009 Springer-Verlag.postprin

Functional tissue engineering of ligament healing

Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Diffusion-controlled swelling of reservoir oil by indirect contact with injection gas

The diffusion-controlled swelling of reservoir oil, when the oil is indirectly contacted by an injection gas such as CO by diffusion through a water barrier film, is presented. The solutions are based on the method of the variable powered profile to describe the distribution of CO in the oil and water phases. This technique greatly reduces the mathematical complexity of the moving boundary problem which is represented by a system of coupled partial differential governing equations, to a system of coupled ordinary differential equations. The present solution is compared with the numerical solution for CO diffusion into an oil phase through a diminishing water barrier. This study demonstrates that the water-blocking phase produces the major mass transfer resistance. The increase in time for the oil phase to saturate with CO is highly non-linear. It increases rapidly with increasing water phase thickness

ROCK TYPING AND PETROPHYSICAL PROPERTY ESTIMATION VIA DIRECT ANALYSIS ON MICROTOMOGRAPHIC IMAGES

ABSTRACT Correlations for petrophysical parameters and saturation dependent transport properties are usually grouped by &quot;rock type&quot;. This is a broad classification including quantitative measures such as porosity, permeability, pore and throat size distributions, pore connectivity and qualitative descriptions of rock fabric and texture. Rock typing is based on conventional core analysis data (porosimetry, permeametry, mercury injection capillary pressure (MICP)), special core analysis (SCAL), wireline logs (electrofacies), description of cuttings and depositional environment, and thin-section analysis. The broad nature of this classification has obvious limitations and fails to fully capture the complex dependence between pore space geometry and topology (rock micro-structure) and petrophysical properties. We propose an alternate classification for rocks based on high resolution X-ray computed microtomography which is complementary to the conventional approach and allows the establishment of a more direct relationship between rock micro-structure and petrophysical properties. Petrophysical properties are computed directly from 3D microtomographic images of clastic and carbonate cores drawn from a wide range of reservoirs. The computed petrophysical properties are used to test empirical correlations between permeability and other important petrophysical parameters (e.g., hydraulic radius, drainage capillary pressure, NMR response, grain size and sorting) for various rock types. We find that the most universally robust correlations are based on the critical pore radius determined from drainage capillary pressure data. The results clearly demonstrate the potential for digital imaging and computations on 3D images to develop improved correlations for petrophysical properties

Entrainment Control Using a Newly Developed Telecentric Inline Probe

This contribution presents a novel approach to investigate entrainment in distillation and absorption columns. An image-based probe allows precise droplet detection at various radial and axial positions above trays. Validations achieve an aver-age error of 6.4 % (monospheres 9.2–114.4mm) and 3 % (monodisperse droplet stream up to 19 m s–1and 74.5mm).Experiments in a DN 450 cold flow test rig show an increasing (decreasing) share of larger droplets with higher gas (liq-uid) loads. Locally measured droplet sizes depend on probe position as well as tray design and enable an extrapolation tointegral entrainment rates