Filippo Boriani

Prolonged Exposure to Hypoxic Milieu Improves the Osteogenic Potential of Adipose Derived Stem Cells

Mesenchymal stem cells (MSC) have been widely used in orthopedics for several applications. Conventionally, MSC are maintained under 21% O2 which does not reflect the real O2 tension in vivo. Recently, it was reported that different O2 conditions can give different cellular responses. Here, we investigated whether prolonged exposure to hypoxia affects the osteogenic differentiation of adipose‐derived stem cells (ASC). ASC from six individuals were cultured under “low” (2–3%) or “air” (21%) oxygen tensions, either without or with osteogenic stimuli. The effect of the O2 tension was evaluated on cell proliferation, surface antigens, stemness and bone‐related genes expression, alkaline phosphatase activity (ALP), mineralization activity, and release of osteogenic growth factors. Without differentiating stimuli, hypoxia favored ASC proliferation, reduced the number of CD184+ and CD34+ cells, and preserved the expression of NANOG and SOX2. The combination of hypoxia and osteogenic medium induced a high proliferation rate, a rapid and more pronounced mineralization activity, a higher expression of genes related to the MSC differentiation, a higher release of mitogenic growth factors (bFGF, PDGF‐BB), and the decrease in TGF‐β secretion, an inhibitor of the early stage of the osteoblast differentiation. We demonstrated that hypoxia acts dually, favoring ASC proliferation and the maintenance of the stemness in the absence of osteogenic stimuli, but inducing the differentiation in a bone‐like microenvironment. In conclusion, prolonged cell culture in hypoxic microenvironment represents a proper method to modulate the stem cell function that may be used in several applications, for example, studies on bone pathophysiology or bone‐tissue engineering. J. Cell. Biochem. 116: 1442–1453, 2015.

Metabolic Effects of Large-Volume Liposuction for Obese Healthy Women: A Meta-Analysis of Fasting Insulin Levels

BackgroundObesity is increasingly frequent in our society and is associated closely with metabolic disorders. As some studies have suggested, removal of fat tissue through liposuction and dermolipectomies may be of some benefit in the improvement of metabolic indices. This article aimed to review the published literature on this topic and to evaluate metabolic variations meta-analytically after liposuction, dermolipectomy, or both.MethodsThrough a literature search with the PubMed/Medline database, 14 studies were identified. All articles were analyzed, and several metabolic variables were chosen in the attempt to meta-analyze the effect of adipose tissue removal through the various studies. All statistical calculations were performed with Review Manager (RevMan), version 5.0.ResultsSeveral cardiovascular and metabolic variables are described as prone to variations after body-contouring procedures when a significant amount of adipose tissue has been excised. Four of the studies included in the analysis reported improvements in all the parameters examined. Seven articles showed improvement in some variables and no improvement in others, whereas three studies showed no beneficial variation in any of the considered indicators after body-contouring procedures. Fasting plasma insulin was identified as the only variable for which a meta-analysis of five included studies was possible. The meta-analysis showed a statistically significant reduction in fasting plasma insulin resulting from large-volume liposuction in obese healthy women.ConclusionMany beneficial metabolic effects resulting from dermolipectomy and liposuction procedures are described in the literature. In particular, fasting plasma insulin and thus insulin sensitivity seem to be positively influenced. Further research, including prospective clinical studies, is necessary for better exploration of the effects that body-contouring plastic surgery procedures have on metabolic parameters.No Level AssignedThis journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

A novel technique for decellularization of allogenic nerves and in vivo study of their use for peripheral nerve reconstruction

Autografts represent the gold standard for peripheral nerve reconstruction but their limited availability, the discrepancy of nerve caliber, and long surgical times are drawbacks. Allografts have therefore become a valid alternative option. In particular, acellular nerve allografts (ANAs) rather than fresh allografts do not need immunosuppression and appear to be safe and effective based on recent studies. An innovative method was conceived to obtain ANAs, so as to speed up nerve decellularization, without compromising nerve architecture, and without breaking the asepsis chain. Several detergent-based techniques, integrated with sonication and mechanical stirring, were tested in vitro on rabbit nerves, to identify, by microscopy and immunohistochemistry, the most effective protocol in terms of cell lysis and cellular debris clearance, while maintaining nerve architecture. Furthermore, a pilot in vivo study was performed: ANAs were implanted into tibial nerve defects of three rabbits, and autografts, representing the gold standard, in other three animals. Twelve weeks postoperatively, rabbits were clinically evaluated and euthanasized; grafts were harvested and microscopically and histomorphometrically analyzed. The method proved to be effective in vitro: the treatment removed axons, myelin and cells, without altering nerve architecture. The in vivo study did not reveal any adverse effect: animals maintained normal weight and function of posterior limb during the entire experimental time. A mild fibrotic reaction was observed, macrophages and leukocytes were rare or absent; ANAs regenerated fascicles and bundles were comparable versus autografts. Based on these results, this decellularization protocol is encouraging and deserves deeper investigations with further preclinical and clinical studies.

Orthoplastics: an evolving concept for integrated surgical care of complex limb trauma and abnormality.

by conducting a more rigorous screening consisting of the plastic surgeon, the anesthesiologist, the pediatrician, the nutritionist, and the dentist on the patient’s first site visit. This ensures that the patient fulfills criteria for surgery, including certain age, hemoglobin, weight, and nutrition requirements, raising the chances of successful surgical intervention.8 On the day of surgery, a team consisting of a surgeon, anesthesiologist, scrub, and circulator works together to repair clefts. This year-round setup leads to a high volume of cleft repair that can facilitate efficiency and better outcomes9; the repetition can expedite the surgical process without compromising safety and potentially can lower the cost per operation. Ultimately, an experience of this sort engenders a collaborative spirit, where all participants take ownership of the patient, striving to overcome any setbacks, all for achieving the overarching goal of delivering the best care to the patient. Furthermore, in the comprehensive care model, the surgeon performing the original operation participates in follow-up care at 1 week, 2 months, and 6 months, permitting continuity of care in an effort to improve patient outcomes. If academic plastic surgeons visit these centers, an incredible exchange of knowledge can occur.10 For example, given the specialization and repetitive nature, some centers tend to perform a selected cleft repair (e.g., Millard rotation advancement, Furlow double Zplasty) with little variation; however, with visiting craniofacial surgeons, other options can be introduced, stimulating change that could be beneficial. Simultaneously, with the cleft center’s tremendous potential clinical volume, quality improvement research investigations with institutional support can be conducted ranging from basic science to clinical outcomes. Above all, the permanent establishment permits the visiting medical professionals the opportunity to return and continue their efforts from where they left off. The comprehensive care center provides a permanent, year-round, high-volume, dedicated cleft facility with a robust screening process and long-term, adequate follow-up that together can improve surgical outcomes. This model could prove to be a paradigm shift in how plastic surgeons will repair clefts as they endeavor to decrease the global surgical burden of disease. DOI: 10.1097/PRS.0b013e31827a294a

Orthoplastic surgical collaboration is required to optimise the treatment of severe limb injuries: A multi-centre, prospective cohort study

Open fractures are severe, complex, limb-threatening and high-energy injuries, often involving lesions of both bone and soft tissues. Traditionally, treatment has been piecemeal by orthopaedic and plastic surgeons. This study aimed to prospectively investigate whether combining orthopaedic and plastic surgery in treating these injuries is more effective than the conventional orthopaedic care. A prospective multi-centre cohort study was conducted. Differences in the type of approach to severe limb trauma allowed a comparison between combined orthoplastic and traditional exclusively orthopaedic treatment. Time for fracture and soft tissue healing and the recovery of limb function were the main outcome measures studied. All patients suffering from a severe open tibial fracture were prospectively included between January 2012 and December 2013 and followed until December 2014. Recruiting units were as follows: (1) an established orthoplastic centre, (2) a unit without experience in the orthoplastic approach and (3) a unit where the orthoplastic approach has been recently introduced in a developing country (Pakistan). A total of 160 patients were included in the study. Of these, 70% were treated with an orthoplastic approach, whereas 30% were treated by an orthopaedic team. All outcome measures were statistically improved by the orthoplastic approach. A coordinated, combined pathway to both the bony and the soft tissue components of open tibial fractures through orthoplastic surgery can be successfully delivered with attention to important timelines to achieve better patient outcomes in different socio-economic settings.

Is the high superior tension technique an equivalent substitute for progressive tension sutures in postbariatric abdominoplasty? A comparison prospective study.

Background: The addition of progressive tension sutures to the abdominoplasty technique is advocated to reduce the risk of several complications. High superior tension abdominoplasty is another technique aimed at reducing tension at the prepubic suture line and improving cosmesis of the umbilical area. Methods: A cohort of massive weight loss patients undergoing abdominoplasty, treated with the progressive tension suture technique in association with the high superior tension technique (group A), was followed up and compared to a cohort of patients who underwent high superior tension abdominoplasty (group B). Several variables including rate of complications and patient satisfaction were explored to determine any possible benefit deriving from the combination of progressive tension suture and high superior tension techniques in the abdominoplasty. Results: A total of 90 patients were included in the study, of whom 34 were in group A and 56 were in group B. No statistically significant difference was found between the two groups in terms of duration of the procedure, hospitalization time, rate of complications, drained volume, and patient or physician satisfaction. Conclusion: No beneficial effect appears to derive from the progressive tension suture technique in massive weight loss patients undergoing abdominoplasty, provided that the high superior tension technique is performed as an adjunct to the traditional method.

Cell-Enhanced Acellular Nerve Allografts for Peripheral Nerve Reconstruction: A Systematic Review and a Meta-Analysis of the Literature

BACKGROUND Peripheral nerve reconstruction is a difficult problem to solve. Acellular nerve allografts (ANAs) have been widely tested and are a promising alternative to the autologous gold standard. However, current reconstructive methods still yield unpredictable and unsuccessful results. Consequently, numerous studies have been carried out studying alternatives to plain ANAs, but it is not clear if nerve regeneration potential exists between current biological, chemical, and physical enrichment modes. OBJECTIVE To systematically review the effects of cell-enhanced ANAs on regeneration of peripheral nerve injuries. METHODS PubMed, ScienceDirect, Medline, and Scopus databases were searched for related articles published from 2007 to 2017. Inclusion criteria of selected articles consisted of (1) articles written in English; (2) the topic being cell-enhanced ANAs in peripheral nerve regeneration; (3) an in vivo study design; and (4) postgrafting neuroregenerative assessment of results. Exclusion criteria included all articles that (1) discussed central nervous system ANAs; (2) consisted of xenografts as the main topic; and (3) consisted of case series, case reports or reviews. RESULTS Forty papers were selected, and categorization included the animal model; the enhancing cell types; the decellularization method; and the neuroregenerative test performed. The effects of using diverse cellular enhancements combined with ANAs are discussed and also compared with the other treatments such as autologous nerve graft, and plain ANAs. CONCLUSION ANAs cellular enhancement demonstrated positive effects on recovery of nerve function. Future research should include clinical translation, in order to increase the level of evidence available on peripheral nerve reconstruction.