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  1. Article ; Online: Mitigation of BMP-induced inflammation in craniofacial bone regeneration and improvement of bone parameters by dietary hesperidin.

    Miguez, Patricia A / de Paiva Gonçalves, Vinícius / Musskopf, Marta L / Rivera-Concepcion, Angeliz / McGaughey, Skylar / Yu, Christina / Lee, Dong Joon / Tuin, Stephen A / Ali, Aya

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 2602

    Abstract: Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n = 10/ ... ...

    Abstract Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n = 10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14 post-surgery. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE + BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 alone caused cystic-like regeneration with incomplete defect closure. HE + BMP2 showed virtually complete bone fusion. Collagen fibril birefringence pattern (red color) under polarized light indicated high organization in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p < 0.05). Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE-treated rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p < 0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE had a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.
    MeSH term(s) Rats ; Animals ; Rats, Sprague-Dawley ; Hesperidin/pharmacology ; X-Ray Microtomography ; Bone Regeneration ; Osteogenesis ; Bone Morphogenetic Protein 2/pharmacology ; Bone Morphogenetic Protein 2/genetics ; Collagen/pharmacology ; Inflammation
    Chemical Substances Hesperidin (E750O06Y6O) ; Bone Morphogenetic Protein 2 ; Collagen (9007-34-5)
    Language English
    Publishing date 2024-01-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-52566-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications.

    Tuin, Stephen A / Pourdeyhimi, Behnam / Loboa, Elizabeth G

    Acta biomaterialia

    2016  Volume 36, Page(s) 220–230

    Abstract: Unlabelled: The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds ... ...

    Abstract Unlabelled: The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds were validated as tissue engineering scaffolds using human adipose derived stem cells (hASC) exposed to pulsatile fluid flow (PFF). The effects of fiber morphology on the proliferation and viability of hASC, as well as effects of varied magnitudes of shear stress applied via PFF on the expression of the early osteogenic gene marker runt related transcription factor 2 (RUNX2) were evaluated. Gilled fiber scaffolds led to a significant increase in proliferation of hASC after seven days in static culture, and exhibited fewer dead cells compared to pure PLA round fiber controls. Further, hASC-seeded scaffolds exposed to 3 and 6dyn/cm(2) resulted in significantly increased mRNA expression of RUNX2 after one hour of PFF in the absence of soluble osteogenic induction factors. This is the first study to describe a method for the fabrication of high surface area gilled fibers and scaffolds. The scalable manufacturing process and potential fabrication across multiple nonwoven and woven platforms makes them promising candidates for a variety of applications that require high surface area fibrous materials.
    Statement of significance: We report here for the first time the successful fabrication of novel high surface area gilled fiber scaffolds for tissue engineering applications. Gilled fibers led to a significant increase in proliferation of human adipose derived stem cells after one week in culture, and a greater number of viable cells compared to round fiber controls. Further, in the absence of osteogenic induction factors, gilled fibers led to significantly increased mRNA expression of an early marker for osteogenesis after exposure to pulsatile fluid flow. This is the first study to describe gilled fiber fabrication and their potential for tissue engineering applications. The repeatable, industrially scalable, and versatile fabrication process makes them promising candidates for a variety of scaffold-based tissue engineering applications.
    MeSH term(s) Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Agaricales ; Cells, Cultured ; Humans ; Pulsatile Flow ; Stem Cells/cytology ; Stem Cells/metabolism ; Tissue Engineering/instrumentation ; Tissue Engineering/methods ; Tissue Scaffolds/chemistry
    Language English
    Publishing date 2016
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2016.03.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Systemic Dietary Hesperidin Modulation of Osteoclastogenesis, Bone Homeostasis and Periodontal Disease in Mice.

    Gonçalves, Vinícius de Paiva / Musskopf, Marta Liliana / Rivera-Concepcion, Angeliz / Yu, Christina / Wong, Sing Wai / Tuin, Stephen A / Jiao, Yizu / Susin, Cristiano / Spolidorio, Luís Carlos / Miguez, Patricia Almeida

    International journal of molecular sciences

    2022  Volume 23, Issue 13

    Abstract: This study aimed to evaluate the effects of hesperidin (HE) on in vitro osteoclastogenesis and dietary supplementation on mouse periodontal disease and femoral bone phenotype. RAW 264.7 cells were stimulated with RANKL in the presence or absence of HE (1, ...

    Abstract This study aimed to evaluate the effects of hesperidin (HE) on in vitro osteoclastogenesis and dietary supplementation on mouse periodontal disease and femoral bone phenotype. RAW 264.7 cells were stimulated with RANKL in the presence or absence of HE (1, 100 or 500 µM) for 5 days, and evaluated by TRAP, TUNEL and Western Blot (WB) analyses. In vivo, C57BL/6 mice were given HE via oral gavage (125, 250 and 500 mg/kg) for 4 weeks. A sterile silk ligature was placed between the first and second right maxillary molars for 10 days and microcomputed tomography (μCT), histopathological and immunohistochemical evaluation were performed. Femoral bones subjected or not to dietary HE (500 mg/kg) for 6 and 12 weeks were evaluated using μCT. In vitro, HE 500 µM reduced formation of RANKL-stimulated TRAP-positive(+) multinucleated cells (500 µM) as well as c-Fos and NFATc1 protein expression (p < 0.05), markers of osteoclasts. In vivo, dietary HE 500 mg/kg increased the alveolar bone resorption in ligated teeth (p < 0.05) and resulted in a significant increase in TRAP+ cells (p < 0.05). Gingival inflammatory infiltrate was greater in the HE 500 mg/kg group even in the absence of ligature. In femurs, HE 500 mg/kg protected trabecular and cortical bone mass at 6 weeks of treatment. In conclusion, HE impaired in vitro osteoclastogenesis, but on the contrary, oral administration of a high concentration of dietary HE increased osteoclast numbers and promoted inflammation-induced alveolar bone loss. However, HE at 500 mg/kg can promote a bone-sparing effect on skeletal bone under physiological conditions.
    MeSH term(s) Alveolar Bone Loss/pathology ; Animals ; Bone Resorption/metabolism ; Cell Differentiation ; Hesperidin/pharmacology ; Homeostasis ; Mice ; Mice, Inbred C57BL ; NFATC Transcription Factors/metabolism ; Osteoclasts/metabolism ; Osteogenesis ; RANK Ligand/metabolism ; X-Ray Microtomography
    Chemical Substances NFATC Transcription Factors ; RANK Ligand ; Hesperidin (E750O06Y6O)
    Language English
    Publishing date 2022-06-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23137100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effect of Flavonoid Supplementation on Alveolar Bone Healing-A Randomized Pilot Trial.

    Souza, Jose Moises / Tuin, Stephen A / Robinson, Adam G / Souza, Joao Gustavo Oliveira de / Bianchini, Marco Aurelio / Miguez, Patricia A

    Dentistry journal

    2020  Volume 8, Issue 3

    Abstract: We investigated the effects of two common dietary supplements on bone healing in dental extraction sockets in humans. In this randomized pilot trial, male subjects took Grape Seed Extract [GSE] or Grapefruit Extract [GFE] starting two weeks prior to ... ...

    Abstract We investigated the effects of two common dietary supplements on bone healing in dental extraction sockets in humans. In this randomized pilot trial, male subjects took Grape Seed Extract [GSE] or Grapefruit Extract [GFE] starting two weeks prior to dental extraction and maintained this regimen for sixty days after surgery. Extraction sockets were filled with a collagen plug. After 24 h, a socket sample was collected and processed for quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and an 84-gene wound healing assay. Sixty days after tooth extraction, a core of newly formed bone was obtained prior to dental implant placement and processed for histology. qRT-PCR revealed that GFE led to a significant decrease in platelet-derived growth factor and interleukin (IL)1-β compared to GSE, and a significant decrease in IL-6 and CXCL2 compared to control. GSE led to a significant increase in coagulation factor Von Willebrand and inflammatory marker IL1-β compared to GFE. WISP1 and CXCL5 were upregulated in both groups. Overall, GFE showed a downregulation of inflammation and GSE led to a decrease in collagen density and increased osteoclasts. This pilot trial highlights the need for further investigation on the mechanism of action of such supplements on bone healing and oral health.
    Language English
    Publishing date 2020-08-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681351-8
    ISSN 2304-6767 ; 2304-6767
    ISSN (online) 2304-6767
    ISSN 2304-6767
    DOI 10.3390/dj8030086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Developing Implantable Scaffolds to Enhance Neural Stem Cell Therapy for Post-Operative Glioblastoma.

    Sheets, Kevin T / Ewend, Matthew G / Mohiti-Asli, Mahsa / Tuin, Stephen A / Loboa, Elizabeth G / Aboody, Karen S / Hingtgen, Shawn D

    Molecular therapy : the journal of the American Society of Gene Therapy

    2020  Volume 28, Issue 4, Page(s) 1056–1067

    Abstract: Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following ... ...

    Abstract Pre-clinical and clinical studies have shown that engineered tumoricidal neural stem cells (tNSCs) are a promising treatment strategy for the aggressive brain cancer glioblastoma (GBM). Yet, stabilizing human tNSCs within the surgical cavity following GBM resection is a significant challenge. As a critical step toward advancing engineered human NSC therapy for GBM, we used a preclinical variant of the clinically utilized NSC line HB1.F3.CD and mouse models of human GBM resection/recurrence to identify a polymeric scaffold capable of maximizing the transplant, persistence, and tumor kill of NSC therapy for post-surgical GBM. Using kinetic bioluminescence imaging, we found that tNSCs delivered into the mouse surgical cavity wall by direct injection persisted only 3 days. We found that delivery of tNSCs into the cavity on nanofibrous electrospun poly-l-lactic acid scaffolds extended tNSC persistence to 8 days. Modifications to fiber surface coating, diameter, and morphology of the scaffold failed to significantly extend tNSC persistence in the cavity. In contrast, tNSCs delivered into the post-operative cavity on gelatin matrices (GEMs) persisted 8-fold longer as compared to direct injection. GEMs remained permissive to tumor-tropic homing, as tNSCs migrated off the scaffolds and into invasive tumor foci both in vitro and in vivo. To mirror envisioned human brain tumor trials, we engineered tNSCs to express the prodrug/enzyme thymidine kinase (tNSCs
    MeSH term(s) Animals ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Brain Neoplasms/therapy ; Cell Line, Tumor ; Combined Modality Therapy ; Ganciclovir/administration & dosage ; Ganciclovir/pharmacology ; Glioblastoma/pathology ; Glioblastoma/surgery ; Glioblastoma/therapy ; Humans ; Luminescent Measurements ; Mice ; Neural Stem Cells/metabolism ; Neural Stem Cells/transplantation ; Polyesters/chemistry ; Prodrugs/administration & dosage ; Prodrugs/pharmacology ; Thymidine Kinase/metabolism ; Tissue Scaffolds/chemistry ; Treatment Outcome ; Xenograft Model Antitumor Assays
    Chemical Substances Polyesters ; Prodrugs ; poly(lactide) (459TN2L5F5) ; Thymidine Kinase (EC 2.7.1.21) ; Ganciclovir (P9G3CKZ4P5)
    Language English
    Publishing date 2020-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2020.02.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Interconnected, microporous hollow fibers for tissue engineering: commercially relevant, industry standard scale-up manufacturing.

    Tuin, Stephen A / Pourdeyhimi, Behnam / Loboa, Elizabeth G

    Journal of biomedical materials research. Part A

    2014  Volume 102, Issue 9, Page(s) 3311–3323

    Abstract: Significant progress has been achieved in the field of tissue engineering to create functional tissue using biomimetic three-dimensional scaffolds that support cell growth, proliferation, and extracellular matrix production. However, many of these ... ...

    Abstract Significant progress has been achieved in the field of tissue engineering to create functional tissue using biomimetic three-dimensional scaffolds that support cell growth, proliferation, and extracellular matrix production. However, many of these constructs are severely limited by poor nutrient diffusion throughout the tissue-engineered construct, resulting in cell death and tissue necrosis at the core. Nutrient transport can be improved by creation and use of scaffolds with hollow and microporous fibers, significantly improving permeability and nutrient diffusion. The purpose of this review is to highlight current technological advances in the fabrication of hollow fibers with interconnected pores throughout the fiber walls, with specific emphasis on developing hollow porous nonwoven fabrics for use as tissue engineering constructs via industry standard processing technologies: Spunbond processing and polymer melt extrusion. We outline current methodologies to create hollow and microporous scaffolds with the aim of translating that knowledge to the production of such fibers into nonwoven tissue engineering scaffolds via spunbond technology, a commercially relevant and viable melt extrusion manufacturing approach that allows for facile scale-up.
    MeSH term(s) Animals ; Biocompatible Materials/chemistry ; Humans ; Porosity ; Stem Cells/cytology ; Tissue Engineering/methods ; Tissue Scaffolds/chemistry
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2014-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2099989-6
    ISSN 1552-4965 ; 1549-3296 ; 0021-9304
    ISSN (online) 1552-4965
    ISSN 1549-3296 ; 0021-9304
    DOI 10.1002/jbma.35002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo.

    Miguez, Patricia A / Tuin, Stephen A / Robinson, Adam G / Belcher, Joyce / Jongwattanapisan, Prapaporn / Perley, Kimberly / de Paiva Gonҫalves, Vinicius / Hanifi, Arash / Pleshko, Nancy / Barton, Elisabeth R

    International journal of molecular sciences

    2021  Volume 22, Issue 6

    Abstract: This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and ... ...

    Abstract This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.
    MeSH term(s) Animals ; Bone Morphogenetic Protein 2/pharmacology ; Bone Regeneration ; Calcification, Physiologic/drug effects ; Cell Line ; Cells, Cultured ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Hesperidin/pharmacology ; Mice ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Osteogenesis/drug effects ; Rats
    Chemical Substances Bmp2 protein, mouse ; Bone Morphogenetic Protein 2 ; Collagen (9007-34-5) ; Hesperidin (E750O06Y6O)
    Language English
    Publishing date 2021-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22063223
    Database MEDical Literature Analysis and Retrieval System OnLINE

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