Effect of platelet mediator concentrate (PMC) on Achilles tenocytes: an in vitro study

Background: Although there are many studies discussing the etiological and pathological factors leading to both, acute and chronic tendon injuries, the pathophysiology of tendon injuries is still not clearly understood. Although most lesions are uncomplicated, treatment is long and unsatisfactory due to the poor vascularity of tendon tissue. Platelet mediator concentrate (PMC) contains many growth factors derived from platelets, which can promote wound healing. In this study we investigate the effects of PMC on tenocyte proliferation and differentiation in order to provide an experimental basis for tissue regeneration strategies and to develop new treatment concepts. Methods: Using enzyme linked immunosorbent assay (ELISA) we were able to quantify the several growth factors and cytokines found in PMC. Tenocytes were isolated both from human and from mouse Achilles tendons and stimulated with PMC. CyQuant((R)) and Cell Titer Blue((R)) assays were carried out to analyze tendon growth and viability at different concentrations of PMC. Real time RT-PCR was used to analyze tenocyte gene expression with or without PMC treatment. Immunohistochemistry was carried out to detect the tenocyte-specific antibody tenomodulin (TNMD) and scleraxis (SCX). Results: We were able to detect numerous mediators such as platelet derived growth factor BB (PDGF- BB), interleukin 6 (IL- 6), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-a), transforming growth factor beta 1 (TGF- beta 1), and bone morphogenetic proteins 2, 4 and 7 (BMP- 4, BMP- 2, BMP- 7) in PMC. It was possible to show a positive effect of PMC on human tendon cell growth and viability in a dose-dependent manner. Furthermore, PMC treatment led to induction of gene expression of scleraxis (SCX), type I collagen A 1 (Col1A1) and TNMD by tenocytes. Conclusions: We suggest that the use of autologous PMC may be a suitable addition to conventional tendon therapy that is capable of increasing and optimizing tendon healing and reducing the risk of recurrence

Discovery of Multifold Modified Sialosides as <i>Human</i> CD22/Siglec‑2 Ligands with Nanomolar Activity on B‑Cells

Sialic acids are abundant in higher domains of life and lectins recognizing sialosaccharides are heavily involved in the regulation of the human immune system. Modified sialosides are useful tools to explore the functions of those lectins, especially members of the Siglec (sialic acid binding immunoglobulin like lectin) family. Here we report design, synthesis, and affinity evaluation of novel sialoside classes with combined modification at positions 2, 4, and 9 or 2, 3, 4, and 9 of the sialic acid scaffold as <i>human</i> CD22 (<i>human</i> Siglec-2) ligands. They display up to 7.5 × 10⁵-fold increased affinity over αMe Neu5Ac (the minimal Siglec ligand). CD22 is a negative regulating coreceptor of the B-cell receptor (BCR). <i>In vitro</i> experiments with a human B-lymphocyte cell line showed functional blocking of CD22 upon B-cell receptor (BCR) stimulation in the presence of nanomolar concentrations of the novel ligands. The observed increased Ca²⁺ response corresponds to enhanced cell activation, providing an opportunity to therapeutically modulate B-lymphocyte responses, e.g., in immune deficiencies and infections

Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products

A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering an underexplored and underrepresented chemical space in fragment based drug discovery (FBDD)

Construction of a 3D-shaped, natural product like fragment library by defragmentation and diversification of natural products

A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of available 3D-shape and natural product like fragments from the available commercial sources. During the course of these studies, a novel rearrangement was discovered for Massarigenin C. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering an underexplored and underrepresented chemical space in fragment based drug discovery (FBDD)

Influence of additional cement augmentation on endplate stability in circumferential stabilisation of osteoporotic spine fractures

Background: Anterior stabilisation of osteoporotic spine fractures is uncommon but necessary in the case of complex vertebral body comminution. The purpose of this study was to investigate the effect of additional cement-augmentation on the endplate stability. Methods: Twelve human cadaveric lumbar spines were divided in two groups: (A) posterior cement-augmented pedicle screw/rod-based instrumentation of L3 to L5, posterior decompression of L4/5 and partial corpectomy of L4 and (B) same experimental setup with additional cement-augmentation of the adjacent endplates. A cyclic loading test was performed at a frequency of 3 Hz, starting with a peak of 500 N for the first 2.000 cycles, up to 950 N for 100.000 cycles under a general preload with 50 N. All specimens were evaluated with regard to a potential collapse of the adjacent endplates. Subsequently, the maximum zero-time failure load of all specimens was determined using a universal testing machine. Findings: The median T-score of bone density was - 4.32 (range - 2.97 to - 5.59), distributed equally in the two groups (average age 83 years). The specimen of the endplate-augmented group showed a significant higher failure load compared to non-endplate-augmented cadavers (group A: 2038 N, group 3: 2990 N, p = 0.03). All specimens passed the full cyclic loading protocol with 100.000 cycles. No significant difference was observable regarding the adjacent endplate subsidence. Interpretation: Additional cement augmentation in circumferential stabilisation resulted in a significant enhancement of the endplate stability regarding the maximum axial load, while the cyclic loading did not significantly enhance the fatigue endurance of the vertebral endplates over the 100,000 cycles tested

Successful Prediction of Substrate-binding Pocket in SLC17 Transporter Sialin

International audienc

Biomechanical effects of posterior pedicle screw-based instrumentation using titanium versus carbon fiber reinforced PEEK in an osteoporotic spine human cadaver model

Background: Aim of this biomechanical investigation was to compare the biomechanical effects of a carbon fiber reinforced PEEK and titanium pedicle screw/rod device in osteoporotic human cadaveric spine. Methods: Ten human fresh-frozen cadaveric lumbar spines (L1-L5) have been used and were randomized into two groups according to the bone mineral density. A monosegmental posterior instrumentation (L3-L4) using titanium pedicle screws and rods was carried out in group A and using carbon fiber reinforced PEEK in group B. A cyclic loading test was performed at a frequency of 3 Hz, starting with a peak of 500 N for the first 2000 cycles, up to 950 N for 100,000 cycles under a general preload with 100 N. All specimens were evaluated with regard to a potential collapse of the implanted pedicle screws. A CT supported digital measurement of cavities around the pedicle at 3 defined measuring points was performed. Finally, the maximum zero-time failure load of all specimens was determined using a universal testing machine (80% F-max). Findings: Regarding maximum axial force (group A: 2835 N, group B: 3006 N, p = 0.595) and maximum compression (group A: 11.67 mm, group B: 15.15 mm, p = 0.174) no statistical difference could be shown between the two groups. However, significant smaller cavity formation around the pedicle screws could be observed in group B (p = 0.007), especially around the screw tip (p < 0.001). Interpretation: Carbon fiber reinforced PEEK devices seem to be advantageous in terms of microscopic screw loosening compared to titanium devices