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Bone regeneration using tissue engineered constructs requires strategies to effectively stimulate vascularization within such a construct that is crucial for its supply and integration with the host tissue. In this work, porous scaffolds of a collagen/hydroxyapatite nanocomposite were modified with heparin to generate biomimetic bone matrices which are able to release angiogenic factors in a controlled manner. Heparin was either integrated during material synthesis (in situ) or added to the scaffolds after their fabrication (post). Both approaches resulted in stable incorporation of heparin into the matrix of mineralized collagen. Investigations of binding and release of the vascular endothelial growth factor (VEGF-A₁₆₅) loaded onto the scaffolds revealed an enhanced binding capacity as well as a sustained and nearly constant delivery of VEGF as result of both heparin modification methods. The release rate could be controlled by varying the quantity of incorporated heparin and the modification method. Although the biological activity of VEGF released after 7 days from the unmodified scaffolds was reduced in comparison to control VEGF, it was maintained after release from post or even enhanced after release from in situ modified scaffolds. In conclusion, the heparin-modified scaffolds of mineralized collagen exhibited favorable growth factor binding and release properties and may be beneficial to stimulate vascularization.

One of the most important requirements for calcium phosphate bone cements (CPBC) is remodelling in vivo. Degradation of the artificial material and the formation of native new bone matrix have to interdigitate to avoid instability. The remodelling process should not last longer than one year. In this study a CPBC was modified with O-phospho-L-serine (phosphoserine) to improve the material properties in order to speed up remodelling in vivo. The results showed that the modified cements exhibit a nano-crystalline microstructure with a high specific surface area and increased compressive strength (about 50 %). Metabolic activity of osteoblasts was improved on the modified material. Monocytes were found to be highly activated on the cements containing phosphoserine. In addition the formation of multinucleated giant cells (osteoclast-like cells) was not impaired on phosphoserine modified cement composites. In vivo experiments in Wistar rats and mini pigs clearly revealed that phosphoserine modified cements showed a higher capability of remodelling compared to the cements without phosphoserine.

Background Chronic granulomatous disease (CGD) patients are susceptible to recurrent opportunistic infections and to recurrent or chronic inflammations of presumably non-infectious origin. Both types of manifestations are often accompanied by granuloma formation. Both can remain unnoticed until they deteriorate considerably and can become life-threatening if not treated in time. Objective To evaluate the effectiveness of regular follow-up visits in CGD patients. Methods Findings of imaging (ultrasound, radiographs, computer-tomography, magnetic resonance imaging), lung function tests, histopathological and microbiological assessments of biopsies have been reviewed. Results A total of 32 CGD patients have been evaluated within 15 years. Of these eight patients have been checked regularly for more than 5 years. Early detection prior to specific clinical signs and consecutive treatment of six lung manifestations and one liver manifestation such as interstitial pneumonia with formation of small granulomas, formation of large granulomas, fibrosis, Aspergillus infections, and abscesses could presumably prevent considerable aggravation in seemingly healthy or mildly symptomatic patients. In contrast, patients without surveillance who presented with severe symptoms (seven manifestations) often had irreversible organ damage or even died. Conclusions Regular follow-up visits can help prevent or mitigate clinical manifestations, improve life quality and expectancy and weigh indication for bone marrow transplantation in CGD patients.

Dominant mutations in the CIAS1 gene cause a spectrum of autoinflammatory diseases such as familial cold autoinflammatory syndrome, FCAS, which is characterized by episodes of urticaria, arthralgia, fever and conjunctivitis after generalized exposure to cold. We here describe patients of two German families with the 592G-->A, V198M mutation, which has been described to induce FCAS before. However, in our patients the clinical phenotype was very different from this disease. They never had urticaria, cold induced fever or conjunctivitis; instead the following symptoms occurred: Very regular periodic fever, irregular severe febrile episodes, relatively mild arthralgia, dry cough, cardiomyopathy, nephropathy and euthyroid thyroiditis all being reversible. We conclude that the clinical phenotype associated with mutations in the CIAS1 gene is much broader than assumed before.

The collection of sputum for microbiological examination in young cystic fibrosis patients can be very difficult. However, a knowledge of bacterial flora colonizing the patient's airways is of paramount importance for proper antimicrobial therapy. It is also known that cystic fibrosis patients colonized by Pseudomonas species have a poorer prognosis than Pseudomonas-negative patients. Noninvasive ways of diagnosing airway inflammation that require only minimal cooperation of the patient might yield new possibilities for early detection of airway colonisation. The breath condensate method as a noninvasive diagnostic technique seems especially appropriate for use in children. Therefore, the aim of this study was to evaluate whether the breath condensate method could be used for detection of Pseudomonas species in children with cystic fibrosis. In total, 32 breath condensate and seven sputum samples were obtained from 13 cystic fibrosis patients with Pseudomonas aeruginosa- or Burkholderia cepacia-positive sputum culture (20 samples were obtained during forced expiration). PCR for combined detection of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia was performed. PCR results of all breath condensate samples were negative for Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Burkholderia cepacia, while all sputum sample results were positive. A minimum DNA quantity of 10 fg could be detected in dilution series of the positive control group. We conclude that the breath condensate method cannot be used as a tool for detection of Pseudomonas species.

Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a deforming arthritis. In the CIAS1 gene of many but not all CINCA patients, disease-associated mutations have been found recently. We here describe two such patients from Germany. One of them, a 3-yr-old boy, has a 1709A-->G, Y570C, mutation, which has previously been described to cause CINCA syndrome. His clinical course is very severe and no satisfying response has been achieved even with high doses of local and systemic steroids. The other patient has a somewhat milder clinical course and considerable improvement could be accomplished with moderate and low doses of steroids. In her CIAS1 gene we have found a 1043C-->T, T348M, mutation, which has only been detected in Muckle-Wells syndrome before. Our results suggest that the severity of symptoms in CINCA patients may be influenced by the underlying mutation in the CIAS1 gene. Furthermore, our observations support the view that CINCA syndrome and Muckle-Wells syndrome are essentially the same disease with different degrees of severity.