Maria Luisa Brandi

University of Florence, Florens, Tuscany, Italy

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Publications (473)1296.64 Total impact

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    ABSTRACT: Purpose: Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities. Methods: A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication. Results: A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia. Conclusions: The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk.
    No preview · Article · Dec 2015 · Aging - Clinical and Experimental Research
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    ABSTRACT: Musculoskeletal diseases are characterized by bone or cartilage defects of regeneration/riparation, lack of healing, uncontrolled/altered proliferation, and so forth. Independent of mechanism, they require a multidisciplinary approach: stem cell-based therapies, manipulation of progenitor cells (such as adipocytes and monocytes), growth factors or hormones, and 3D structures and scaffolds. Some of these strategies are clearly understood and applied, while others have been studied but as yet not well determined. MicroRNAs (miRNAs) negatively regulate the post-transcriptional expression of target genes involved in bone metabolism. These pathways involve the differentiation of osteoblasts, osteoclasts, fat cells, and chondrocytes, and their interactions with biomaterials. This chapter explores the relationship of miRNAs and bone disease and the future development of miRNA-based therapeutic strategies for treatment.
    No preview · Chapter · Dec 2015
  • Luisella Cianferotti · Maria Luisa Brandi
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    ABSTRACT: Non-surgical, inherited hypoparathyroidism consists of a group of heterogeneous disorders characterized by hypocalcemia and hyperphosphatemia resulting from inadequate PTH synthesis, secretion, or action. Hypoparathyroidism may present as the sole manifestation or in combination with additional features. Until 20 years ago they were mainly referred to as idiopathic hypoparathyroidism, since genetic tests were not available. In the last two decades, the molecular basis of many of the isolated and familial forms of the disease has been unraveled and accurate and targeted cytogenetic/genetic analyses are now available to better classify and consequently improve clinical management. In parallel, mouse models of the corresponding diseases have been generated, helping to define and dissect in vivo the newly identified molecular pathways. The identification of genes important for parathyroid development, differentiation and function and the steadily growing research in this field have shed light on new regulators of mineral metabolism.
    No preview · Chapter · Dec 2015
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    ABSTRACT: Primary hyperparathyroidism is a common endocrine disease that has undergone a series of changes in its clinical presentation over the past 60 years. The form of primary hyperparathyroidism (PHPT) that is seen most often in countries where biochemical screening is routine is described as “asymptomatic” because these individuals do not have classical signs and symptoms that are typically associated with hypercalcemia or high levels of parathyroid hormone. Four international workshops on the management of this form of PHPT have been held: 1991, 2002, 2008, and 2013. In this chapter, we present the results of the 2013 conference that led to a revision of the 2008 guidelines. It constitutes an update of evidence-based information about diagnostics, clinical features, and management of this disease. The conference also highlighted areas for which research is needed to clarify issues that remain uncertain or controversial.
    No preview · Chapter · Dec 2015
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    ABSTRACT: Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake.
    Preview · Article · Dec 2015 · Nutrients
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    ABSTRACT: The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, which provides practical guidance for the prioritization of interventions. Further analysis of real world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g. delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This paper provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians’ individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.
    Full-text · Article · Dec 2015 · Seminars in Arthritis and Rheumatism
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    ABSTRACT: Bone tissue engineering is an emerging field, representing one of the most exciting challenges for scientists and clinicians. The possibility of combining mesenchymal stem cells and scaffolds to create engineered tissues has brought attention to a large variety of biomaterials in combination with osteoprogenitor cells able to promote and regenerate bone tissue. Human adipose tissue is officially recognized as an easily accessible source of mesenchymal stem cells (AMSCs), a significant factor for use in tissue regenerative medicine. In this study, we analyze the behavior of a clonal finite cell line derived from human adipose tissue seeded on poly( ε -caprolactone) (PCL) film, prepared by solvent casting. PCL polymer is chosen for its good biocompatibility, biodegradability, and mechanical properties. We observe that AMSCs are able to adhere to the biomaterial and remain viable for the entire experimental period. Moreover, we show that the proliferation process and osteogenic activity of AMSCs are maintained on the biofilm, demonstrating that the selected biomaterial ensures cell colonization and the development of an extracellular mineralized matrix. The results of this study highlight that AMSCs and PCL film can be used as a suitable model to support regeneration of new bone for future tissue engineering strategies.
    Full-text · Article · Nov 2015
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    ABSTRACT: Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.
    No preview · Article · Oct 2015 · Calcified Tissue International
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    ABSTRACT: Primary hyperparathyroidism (HPT) is the most common endocrinopathy in Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Supernumerary and/or ectopic parathyroid glands, potentially causes of persistent or recurrent HPT after surgery, have been previously described. However, this is the first ever described case of ectopic parathyroid gland localized in the aortopulmunary window causing HPT in MEN1. After a consistent concordant pre-operative imaging assessment the patient, a 16 years old male affected by a severe hypercalcemia, underwent surgery. The parathyroid was found very deeply near the tracheal bifurcation, hidden by the aortic arch itself and for this reason not visible at the beginning of the dissection but only after being identified by palpation for its typical consistence. The intraoperative PTH decreased at normal level 10 min after removal of the ectopic gland. The patient remained with normal value of calcemia and PTH during the 10 months of follow-up.
    No preview · Article · Sep 2015 · Familial Cancer
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    ABSTRACT: Primary hyperparathyroidism is the main endocrinopathy associated with Multiple Endocrine Neoplasia type 1 syndrome. Cinacalcet is a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease, and for the reduction of marked hypercalcemia in patients with parathyroid carcinoma and sporadic hyperparathyroidism requiring surgery but for whom parathyroidectomy is contraindicated. It may provide a medical alternative for the management of primary hyperparathyroidism in subjects affected by Multiple Endocrine Neoplasia type 1. In this longitudinal, intervention study, 33 MEN1 patients had been enrolled, 10 males and 23 females with a mean age of 40 ± 11.9 years, range 20-63. Primary hyperparathyroidism was the first clinical manifestation in 12 patients. All subjects commenced with Cinacalcet 30 mg/day, 22 patients starting therapy with calcimimetics as an alternative to surgery, and 11 patients opting for the medication after the onset of persistent post-surgical primary hyperparathyroidism. Duration of follow-up was 12 months. The results of this study show significant reductions in serum calcium. The changes in hormonal secretions of pituitary and gastroenteropancreatic glands were not significant, demonstrating the overall safety of this drug in this disease. Cinacalcet has been well tolerated by 28 patients, whereas five individuals complained of heartburn and grade 1 nausea, which did not prevent the completion of the study. In conclusion, Cinacalcet has resulted to be well tolerated and safe in patients with MEN1 syndrome and the calcium homeostasis was stabilized.
    No preview · Article · Jul 2015 · Endocrine
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    ABSTRACT: Osteoporosis is as a very complex multi-factorial pathogenesis; thereby any doctor facing a case of osteoporosis must be very careful. Diagnostic procedures are complex and include careful monitoring of the history of patient, physical examination and some laboratory analysis. In this study, 201 patients aged between 50 and 95 years were selected from 4872 patients consulting orthopedic clinics. This group (201 patients: 168 women, 33 men) showed evidence of osteoporosis: BMD DXA with reduced bone
    Full-text · Article · Jul 2015
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    ABSTRACT: Parathyroid hormone (PTH) is important in the assessment of calcium metabolism disorders. However, there are few data regarding PTH levels in childhood and adolescence. The aim of this study was to determine PTH levels in a large group of healthy children and adolescents. We retrospectively evaluated PTH levels in 1,580 healthy Caucasian children and adolescents (849 females, 731 males, aged 2.0-17.2 years) with 25-hydroxyvitamin D [25(OH)D] levels ≥30 ng/ml. All subjects with genetic, endocrine, hepatic, renal, or other known diseases were excluded. The serum intact PTH concentration (median and inter-quartile range) was 23.00 (15.00-31.60) pg/ml. In our population, the mean 25(OH)D value was 34.27 ± 4.12 ng/ml. The median PTH concentration in boys was 23.00 (15.00-32.00) pg/ml, whereas in girls it was 23.10 (15.00-31.10) pg/ml. However, in girls, PTH levels significantly increased in the age group of 8.1-10.0 years compared to the age group of 2.1-4.0 years (p < 0.0001), whereas in boys it significantly increased in the age groups of 10.1-12.0 years (p < 0.0001) and 12.1-14.0 years (p < 0.0001), leading to the hypothesis of a relationship between PTH level and pubertal and bone growth spurts. PTH levels in healthy children and adolescents covered a narrower range than the adult values. Obtaining reference values of PTH in childhood and adolescence could aid in the estimation of appropriate values of bone metabolites. © 2015 S. Karger AG, Basel.
    No preview · Article · Jun 2015 · Hormone Research in Paediatrics
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    ABSTRACT: Commonly, health behaviour theories have been applied to single behaviours, giving insights into specific behaviours but providing little knowledge on how individuals pursue an overall healthy lifestyle. In the context of diet and physical activity, we investigated the extent to which cross-behaviour cognitions, namely transfer cognitions and compensatory health beliefs, contribute to single behaviour theory. A total of 767 participants from two European regions (i.e., Germany n = 351, southern Europe n = 416) completed online questionnaires on physical activity and healthy dietary behaviour, behaviour-specific cognitions (i.e., self-efficacy, outcome expectancies, risk perception, intention, action planning, action control), as well as cross-behaviour cognitions, namely transfer cognitions and compensatory health beliefs. Nested path models were specified to investigate the importance of cross-behaviour cognitions over and above behaviour-specific predictors of physical activity and healthy nutrition. Across both health behaviours, transfer cognitions were positively associated with intention and self-regulatory strategies. Compensatory health beliefs were negatively associated with intention. Action planning and action control mediated the effect of intentions on behaviour. Cross-behaviour cognitions contribute to single behaviour theory and may explain how individuals regulate more than one health behaviour. Statement of contribution What is already known on this subject? Cross-behaviour cognitions are related to a healthy lifestyle. Compensatory health beliefs hinder the adoption of a healthy lifestyle. Transfer cognitions encourage the engagement in a healthy lifestyle. What does this study add? Transfer cognitions were positively associated with intentions, action planning, and action control over and above behaviour-specific cognitions. Compensatory health beliefs were related to intentions only. Both facilitating and debilitating cross-behaviour cognitions need to be studied within a unified multiple behaviour research framework. © 2015 The British Psychological Society.
    No preview · Article · Jun 2015 · British Journal of Health Psychology
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    ABSTRACT: Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates.
    Full-text · Article · Jun 2015
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    ABSTRACT: Hypophosphatemic rickets (HR) is a rare disease that includes a group of hereditary and sporadic conditions characterized by renal phosphate loss associated with normal to low vitamin D serum concentration. The most common form is the X-linked hypophosphatemic rickets, with an incidence of 1: 20000. Several mutations have recently been identified in PHEX, FGF23, DMP1 and ENPP1 genes in patients with HR. Moreover, in vitro and in vivo studies suggested an involvement of MEPE for defective mineralization in HR. The present case series describes the clinical features and the analysis of genes implicated in HR in a cohort of 26 Italian HR patients. All patients were analyzed for PHEX and FGF23 genes by direct sequencing. When no mutations were detected, Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed. The negative patients were screened for DMP1, MEPE and ENPP1 genes by direct sequencing. Twenty-two patients (84%) harbored mutations in PHEX gene. In particular, we detected 19 different mutations, 15 of which were novel. One patient presented a novel splice variation in ENPP1 gene while no alterations were identified in FGF23, DMP1 and MEPE genes. The genetic study of the families showed that 11 patients (55%) had de novo mutations. Clinical presentation and disease severity did not show an evident correlation between the mutation type. This report represents the first large familial study performed on Italian patients. It confirms that mutations in PHEX are the most frequent cause of HR. Furthermore, the variety of clinical manifestations identified in our HR patients underlines the extreme clinical and genetic heterogeneity of this disease. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Bone
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    ABSTRACT: A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive. The Fracture Prevention Service (FPS), a tailored in-hospital model of care, may effectively bridge the osteoporosis care gap for hip-fractured older persons. The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment. This was a prospective observational study conducted in a teaching hospital with traumatology and geriatric units, and had a pre-intervention and post-intervention phase. The records of 172 participants were evaluated in the pre-intervention phase, while data from 210 participants were gathered in the post-intervention phase. All participants underwent telephone follow-up at 12 months after hospital discharge. The participants were patients aged ≥65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture. A multidisciplinary integrated model of care was established. Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons, improve their evaluation through bone mineral density testing and blood examinations, and initiate an appropriate treatment for secondary prevention of falls and fragility fractures. Compared with the pre-intervention phase, more hip-fractured persons received bone mineral density testing (47.62% versus 14.53%, P<0.0001), specific pharmacological treatments (48.51% versus 17.16%, P<0.0001), and an appointment for evaluation at a fall and fracture clinic (52.48% versus 2.37%, P<0.0001) in the post-intervention phase. Independent of some confounders, implementation of the FPS was positively associated with recommendations for secondary fracture prevention at discharge (P<0.0001) and with 1-year adherence to pharmacological treatment (P<0.0001). The FPS is an effective multidisciplinary integrated model of care to optimize identification of older persons at highest risk for fragility fracture, to improve their clinical management, and to increase adherence to prescriptions.
    Full-text · Article · Jun 2015 · Clinical Interventions in Aging
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    ABSTRACT: Several compounds are produced along the complex pathways of vitamin D3 metabolism, and synthetic analogs have been generated to improve kinetics and/or vitamin D receptor activation. These metabolites display different chemical properties with respect to the parental or native vitamin D3, i.e., cholecalciferol, which has been, so far, the supplement most employed in the treatment of vitamin D inadequacy. Hydrophilic properties of vitamin D3 derivatives facilitate their intestinal absorption and their manageability in the case of intoxication because of the shorter half-life. Calcidiol is a more hydrophilic compound than parental vitamin D3. Active vitamin D analogs, capable of binding the vitamin D receptor evoking vitamin D-related biological effects, are mandatorily employed in hypoparathyroidism and kidney failure with impaired 1α-hydroxylation. They have been shown to increase BMD, supposedly ameliorating calcium absorption and/or directly affecting bone cells, although their use in these conditions is jeopardized by the development of hypercalciuria and mild hypercalcemia. Further studies are needed to assess their overall safety and effectiveness in the long-term and new intermittent regimens, especially when combined with the most effective antifracture agents.
    No preview · Article · May 2015 · Endocrine
  • Luisella Cianferotti · Caterina Fossi · Maria Luisa Brandi
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    ABSTRACT: Hip fractures are one of the most serious conditions in frail elderly subjects, greatly increasing morbidity and mortality, and decreasing healthy life years. Since their first introduction on the market, hip protectors have been revealed to be a potential preventive measure for hip fractures, in addition to other well-known recognized medical interventions and rehabilitation procedures. However, randomized controlled trials have given contradictory results regarding their efficacy. Moreover, little data are available on the cost effectiveness of hip protectors. Adherence is a major problem in assessing the effectiveness of hip protectors in preventing fractures. Indeed, there is a lack of general consensus on a standard definition and quantitative objective estimation of adherence to hip protectors, along with still scarce evidence on specific interventions on how to ameliorate it. From what is known so far, it seems reasonable to advise the use of hip protectors in aged care facilities, since recent pooled analyses have suggested their efficacy in this setting. The introduction of sensors combined with hip protectors will probably address this issue, both for monitoring and optimizing compliance, especially in elderly people. In the meantime, new, well-designed studies following specific guidelines are strongly encouraged and needed. In particular, studies in community-dwelling elderly individuals at high risk of first or further fragility fractures are required. The optimization of the tested devices in a preclinical setting according to international standard biomechanical testing is necessary.
    No preview · Article · Apr 2015 · Calcified Tissue International
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    ABSTRACT: Bone tissue engineering represents a challenge in regenerative medicine. Many types of materials have been studied as scaffolds in combination with mesenchymal stem cells, in order to develop viable substitutes able to restore and maintain the function of human bone tissues in skeletal defects. In this work, we have evaluated the viability, the adhesion and the proliferation of human adipose-derived stem cells (hADSCs) in association with poli(Ɛ-caprolactone), PCL, a biodegradable polyester, for future application in regenerative medicine. After the Local Ethical Committee approval, human adipose tissue was minced and digested at 37°C in 3 mg/ml collagenase type I, for three hours. Primary cells were cultured in growth medium (10% FBS, 1 ng/ml bFGF and 1% antibiotics) at 37°C and 5% CO2. Characterized hADSCs, (CD44+, CD105+, STRO1+ and CD45-), were plated on PCL film to evaluate fibronectin adhesion protein and cytoskeleton, by immunocytochemistry, using laser scanning confocal microscopy. Cell viability and proliferation were analyzed by Acridine Orange (AO) staining and MTT assay on days 2, 4, 7, 10, 13, 16 after cell seeding on PCL film at appropriate density (5 x 103). Statistical analysis was performed by linearity test. No qualitative differences were found in cell adhesion and cytoskeleton fiber morphology between hADSCs grown on PCL film and hADSCs grown on polystyrene, used as control. MTT assay has measured a consistent growth of absorbance during all the studied period for hADSCs seeded on PCL (linear regression r2= 0,86), suggesting that good cell viability was achieved on biomaterial. Cytocompatibility was also confirmed by AO staining microscopic observations. PCL construct has shown encouraging results in terms of cell adhesion and viability of hADSCs, opening new possibilities for future application in bone tissue engineering. Experiments are in progress in order to evaluate the osteogenic differentiation process of hADSCs on PCL. Acknowledgment This work was supported by Regione Toscana-POR CREO FESR 2007-2013.BANDO UNICO R&S 2012, linea A. Decreto dirigenziale n. 2746, 17/06/2014. Progetto REOSS.
    No preview · Conference Paper · Apr 2015
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    Full-text · Presentation · Apr 2015

Publication Stats

9k Citations
1,296.64 Total Impact Points


  • 1985-2015
    • University of Florence
      • • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      • • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      • • Dipartimento di Medicina Sperimentale e Clinica
      Florens, Tuscany, Italy
  • 2014
    • Euro Mediterranean Scientific and Biomedical Institute
      Brindisi, Apulia, Italy
  • 2013
    • Misericordia of Florence
      Florens, Tuscany, Italy
  • 2012
    • Santa Maria del Pozzo
      Napoli, Campania, Italy
  • 2007
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
  • 2006
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • Azienda Ospedaliero Universitaria Careggi
      • Department of Internal Medicine
      Firenzuola, Tuscany, Italy
  • 2002
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 1994-1998
    • Università degli studi di Parma
      • Dipartimento di Scienze Chirurgiche
      Parma, Emilia-Romagna, Italy
  • 1995
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1986-1989
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States