The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (<45 a). 5-hydroxymethylcytosine (5 hmC) and 5-methylcytonsine (5 mC) distribution as well as TET gene expression were evaluated to assess the evidence of active DNA demethylation. We observed a decrease of 5 hmC in Ad-MSCs from older donors. Incubation of these cells with 5-Azacytidine induced proliferation and improved the osteogenic differentiation potential in these cells. The increase in AP activity and matrix mineralization was associated with an increased presence of 5 hmC as well as with an increased TET2 and TET3 gene expression. Our data show, for the first time, a decrease of DNA hydroxymethylation in Ad-MSCs which correlates with donor-age and that treatment with 5-Azacytidine provides an approach which could be used to rejuvenate Ad-MSCs from aged donors.

Background: Despite advances in the monitoring of free flaps, there is still a demand for new technology to detect ischemic complications at an early stage. The aim of the present study was to evaluate the reliability of the O2C-device in terms of detecting flap failure in commonly used perforator flaps for breast reconstruction. Methods: A total of 34 patients undergoing breast reconstruction were involved in this study. The perfusion dynamics of 23 deep inferior epigastric perforator flaps and 11 superior gluteal arterial perforator flaps were assessed using the O2C-device, which combines a laser light, to determine blood flow (flow), velocity, and white light to determine hemoglobin oxygenation (SO 2 ) and relative amount of hemoglobin (rHB). Measurements were carried out intra-operatively after clamping and declamping the perforator vessels. In the post-operative period measurements were carried out every hour for the first 48 hours and from 3rd to 7th for every 2 hours. These dates were compared to findings of clinical assessment. Results: Several intra-operative measurements, during the clamping and declamping the different perforator vessels, revealed a high correlation for all parameters: Flow (r 5 0.89, P < 0. 05), Velo (r 5 0.92, P < 0. 05), SO 2 (r 50.84, P <0. 05), and rHB (r 50.83 P < 0.05). Vessel occlusion was detected in five cases, of which three were due to arterial thrombosis and two further cases were due to venous occlusion. Of the five cases, one flap loss caused by venous occlusion was noted. Conclusion: The O2C-device seems to be a reliable, objective, and non-invasive device for the monitoring of free flaps. Thus, it may improve flap survival rates by detecting vascular compromise at an early stage. V V C 2013 Wiley Periodicals, Inc. Microsurgery 33: 350-357, 2013.

The authors' combined study showed varying perfusion characteristics between anatomical and clinical settings, which could be caused by a number of complex systemic and local processes. Thus, the selection of the DIEP zones should be assessed individually depending on the anatomy in question and the characteristics of the perforators until the mentioned issues are clarified in detail.

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BackgroundWe systematically reviewed etiological factors of Kienböck’s disease (osteonecrosis of the lunate) discussed in the literature in order to examine the justification for including Kienböck’s disease (KD) in the European Listing of Occupational Diseases.MethodsWe searched the Ovid/Medline and the Cochrane Library for articles discussing the etiology of osteonecrosis of the lunate published since the first description of KD in 1910 and up until July 2012 in English, French or German. Literature was classified by the level of evidence presented, the etiopathological hypothesis discussed, and the author's conclusion about the role of the etiopathological hypothesis. The causal relationship between KD and hand-arm vibration was elucidated by the Bradford Hill criteria.ResultsA total of 220 references was found. Of the included 152 articles, 140 (92%) reached the evidence level IV (case series). The four most frequently discussed factors were negative ulnar variance (n=72; 47%), primary arterial ischemia of the lunate (n=63; 41%), trauma (n=63; 41%) and hand-arm vibration (n=53; 35%). The quality of the cohort studies on hand-arm vibration did not permit a meta-analysis to evaluate the strength of an association to KD. Evidence for the lack of consistency, plausibility and coherence of the 4 most frequently discussed etiopathologies was found. No evidence was found to support any of the nine Bradford Hill criteria for a causal relationship between KD and hand-arm vibration.ConclusionsA systematic review of 220 articles on the etiopathology of KD and the application of the Bradford Hill criteria does not provide sufficient scientific evidence to confirm or refute a causal relationship between KD and hand-arm vibration. This currently suggests that, KD does not comply with the criteria of the International Labour Organization determining occupational diseases. However, research with a higher level of evidence is required to further determine if hand-arm vibration is a risk factor for KD.

The demand for scaffolds comprised of natural materials such as collagen has increased in recent years. However, many scaffolds rely on chemical or physical modifications in order to comply with the necessary requirements for biomedical engineering. We evaluated the in vivo biocompatibility and biodegradation of a novel, thin, mechanically stable, and chemically non-crosslinked collagen cell carrier (CCC). CCC was implanted subcutaneously into 25 adult Lewis rats and biopsies were taken on days 7, 14, 21, 42, and 84 after surgery. For histological analysis, paraffin sections of implanted skin were immunolabeled for CD68 and stained by hematoxylin-eosin and Masson-Goldner's trichrome method. Macroscopic analysis of skin surface during wound healing process showed a normal physiological reaction. Biodegradation of CCC was completed 42 days after subcutaneous implantation. Histological evaluation revealed no evidence of encapsulation, scar formation, or long-term vascularization and inflammation. The collagen type I based biomaterial demonstrated a high in vivo biocompatibility, low irritability, complete resorption, and replacement by autologous tissue. The in vivo biocompatibility and degradation behavior encourage for further evaluation of CCC in surgical applications and regenerative medicine.

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Fibulo-scapho-lunate fusion is an elegant method of distal radius reconstruction with good functional outcome and low risk of pulmonary metastasis.