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    Item type:Publication,
    Polycaprolactone-based scaffolds for guided tissue regeneration in periodontal therapy: A systematic review
    (2023)
    Florencia Antunovic
    ;
    Felipe Tolosa
    ;
    Catherine Klein
    ;
    René Ocaranza
    <jats:sec><jats:title>Background:</jats:title><jats:p> Polycaprolactone (PCL) is a highly recognized synthetic polymer for its biocompatibility, ease of fabrication and mechanical strength in bone tissue engineering. Its applications have extended broadly, including regeneration of oral and maxillofacial lost tissues. Its usefulness has brought attention of researchers to regenerate periodontal lost tissues, including alveolar bone, periodontal ligament and cementum. The aim of this systematic review was to obtain an updated analysis of the contribution of PCL-based scaffolds in the alveolar bone regeneration process. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> This review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews. A computerized search of the PubMed, EBSCO, Scielo and Web of Science databases was performed, restricting literature search to published studies in English or Spanish between January 2002 and March 2023. Database search returned 248 studies which were screened based on title, author names and publication dates. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Data from 17 studies were reviewed and tabulated. All studies combined PCL with other biomaterials (such as Alginate, hydroxyapatite, bioactive glass, poly (lactic-co-glycolic acid)), growth factors (BMP-2, rhCEMP1), and/or mesenchymal stromal cells (adipose-derived, bone marrow, periodontal ligament or gingiva mesenchymal stromal cells). PCL scaffolds showed higher cell viability and osteoinductive potential when combined with bioactive agents. Complementary, its degradation rates were affected by the addition or exposure to specific substances, such as: Dopamine, Cerium Oxide, PLGA and hydrogen peroxide. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> PCL is an effective biomaterial for alveolar bone regeneration in periodontally affected teeth. It could be part of a new generation of biomaterials with improved regenerative potential. </jats:p></jats:sec>
    Scopus© Citations 15
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    Item type:Publication,
    Human adipose-derived mesenchymal stem cell-conditioned medium ameliorates polyneuropathy and foot ulceration in diabetic BKS db/db mice
    (2020) ; ;
    Cristian Acosta
    ;
    Diego Díaz
    ;
    Constanza Cárcamo
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Diabetic polyneuropathy (DPN) is the most common and early developing complication of diabetes mellitus, and the key contributor for foot ulcers development, with no specific therapies available.</jats:p> <jats:p>Different studies have shown that mesenchymal stem cell (MSC) administration is able to ameliorate DPN; however, limited cell survival and safety reasons hinder its transfer from bench to bedside. MSCs secrete a broad range of antioxidant, neuroprotective, angiogenic, and immunomodulatory factors (known as conditioned medium), which are all decreased in the peripheral nerves of diabetic patients. Furthermore, the abundance of these factors can be boosted in vitro by incubating MSCs with a preconditioning stimulus, enhancing their therapeutic efficacy. We hypothesize that systemic administration of conditioned medium derived from preconditioned MSCs could reverse DPN and prevent foot ulcer formation in a mouse model of type II diabetes mellitus.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Diabetic BKS <jats:italic>db/db</jats:italic> mice were treated with systemic administration of conditioned medium derived from preconditioned human MSCs; conditioned medium derived from non-preconditioned MSCs or vehicle after behavioral signs of DPN was already present. Conditioned medium or vehicle administration was repeated every 2 weeks for a total of four administrations, and several functional and structural parameters characteristic of DPN were evaluated. Finally, a wound was made in the dorsal surface of both feet, and the kinetics of wound closure, re-epithelialization, angiogenesis, and cell proliferation were evaluated.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Our molecular, electrophysiological, and histological analysis demonstrated that the administration of conditioned medium derived from non-preconditioned MSCs or from preconditioned MSCs to diabetic BKS <jats:italic>db/db</jats:italic> mice strongly reverts the established DPN, improving thermal and mechanical sensitivity, restoring intraepidermal nerve fiber density, reducing neuron and Schwann cell apoptosis, improving angiogenesis, and reducing chronic inflammation of peripheral nerves. Furthermore, DPN reversion induced by conditioned medium administration enhances the wound healing process by accelerating wound closure, improving the re-epithelialization of the injured skin and increasing blood vessels in the wound bed in a skin injury model that mimics a foot ulcer.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Studies conducted indicate that MSC-conditioned medium administration could be a novel cell-free therapeutic approach to reverse the initial stages of DPN, avoiding the risk of lower limb amputation triggered by foot ulcer formation and accelerating the wound healing process in case it occurs.</jats:p> </jats:sec>
      1Scopus© Citations 79  4
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    Item type:Publication,
    Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia
    (2020)
    Nancy Farfán
    ;
    Jaime Carril
    ;
    Martina Redel
    ;
    Marta Zamorano
    ;
    Maureen Araya
    <jats:p>Perinatal Asphyxia (PA) is a leading cause of motor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-α+IFN-γ (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °C for 21 min. Thereafter, 16 μL of MSC-S (containing 6 μg of protein derived from 2 × 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-κB/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia.</jats:p>
    Scopus© Citations 28  9