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11 pages, 841 KB  
Review
Contemporary Concepts and Techniques for Scar Minimization in Direct Brow Lift: A Literature Review
by Ayyad Zartasht Khan, Lars Christian Boberg-Ans, Fredrik Andreas Fineide, Richard Cutler Allen, Elin Bohman, Kim Alexander Tønseth, Hania Nadeem Karamat and Tor Paaske Utheim
J. Clin. Med. 2026, 15(12), 4445; https://doi.org/10.3390/jcm15124445 - 9 Jun 2026
Viewed by 501
Abstract
Background: Despite the rise of endoscopic approaches, the direct brow lift remains one of the most effective procedures for correcting brow ptosis for both functional and cosmetic indications. It continues to offer superior control when correcting brow shape, height, and asymmetry. However, [...] Read more.
Background: Despite the rise of endoscopic approaches, the direct brow lift remains one of the most effective procedures for correcting brow ptosis for both functional and cosmetic indications. It continues to offer superior control when correcting brow shape, height, and asymmetry. However, visible scarring remains a concern. This systematic review was conducted to synthesize recent evidence on strategies that minimize visible scarring in direct brow lift surgery. Methods: A systematic literature search was performed to retrieve English-language publications from the past decade, discussing scar-minimization strategies in direct brow lift. A total of 124 records were identified through database searches in Ovid MEDLINE and Embase. Records were screened manually according to predetermined criteria, and those not in English, not addressing scarring, or not focused on direct brow lift were excluded. After this process, ten publications were included in the final qualitative synthesis. Results: The qualitative synthesis of all included publications (together comprising data on approximately 900 patients) revealed several strategies for scar minimization. (1) Incision beveling: A shallow cranially directed bevel between 20° and 45° preserves brow hair follicles and allows hair regrowth through the scar, providing natural camouflage. (2) Undermining: Gentle subcutaneous undermining in a limited 1–2 cm field, while preserving subcutaneous fat, allows tension-free advancement and maintains brow volume. (3) Periosteal suspension: Anchoring the mobilized brow flap to the frontal periosteum redistributes tension away from the dermal closure, maintaining elevation and improving scar quality. (4) Layered closure: Two- or three-layered wound closure with deep dermal anchoring and fine everting skin sutures minimizes dermal traction and scar widening. (5) Adjunctive measures: Evidence for topical silicone gel was inconclusive, whereas postoperative laser therapy and perioperative neuromodulator use demonstrated improved scar appearance. Across studies, outcomes were consistent, with high patient satisfaction, inconspicuous scars in over 85% of cases, and low complication or revision rates. Conclusions: Direct brow lift has historically been criticized for conspicuous scarring, contributing to the popularity of endoscopic techniques. Nevertheless, the traditional direct brow lift remains a fundamental skill in the oculofacial plastic surgeon’s armamentarium, offering unmatched accuracy in brow repositioning, reliability, and symmetry. Contemporary evidence demonstrates refinements that can markedly minimize scar visibility. This systematic review and qualitative synthesis allow us to continue to refine and improve our techniques to minimize scarring in direct brow lift to the benefit of our patients. Full article
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26 pages, 8307 KB  
Case Report
Parry–Romberg Syndrome: Radioclinical Dissociation in a Paucisymptomatic Form and a Proposed Diagnostic Framework
by Cristian Turlea, Andrei I. Cucu, Alexandru Carauleanu, Roxana Covali, Camelia Tamas, Mihnea A. Popa, Victor Constantinescu, Anca P. Morosan, Elena Porumb-Andrese, Iulian Prutianu, Claudia F. Costea, Amelian Bobu, Adriana Hristea and Alexandru Nemtoi
Diagnostics 2026, 16(8), 1219; https://doi.org/10.3390/diagnostics16081219 - 19 Apr 2026
Cited by 1 | Viewed by 2976
Abstract
Background and Clinical Significance: Parry–Romberg syndrome (PRS), also known as progressive hemifacial atrophy, is a rare disorder characterized by progressive unilateral hemifacial atrophy, with potential involvement of the cranial bones and the brain. Although neurological manifestations are frequently described, central nervous system involvement [...] Read more.
Background and Clinical Significance: Parry–Romberg syndrome (PRS), also known as progressive hemifacial atrophy, is a rare disorder characterized by progressive unilateral hemifacial atrophy, with potential involvement of the cranial bones and the brain. Although neurological manifestations are frequently described, central nervous system involvement may be subclinical and detectable only through neuroimaging. Owing to its rarity and the lack of standardized diagnostic criteria, most available data derive from case reports and small case series. Case Presentation: We report the case of a 38-year-old female patient diagnosed with PRS (stage 2 according to the Guerrerosantos classification), with onset in childhood characterized by left parietal alopecia, followed by progressive left-sided hemifacial atrophy and a linear “en coup de sabre” lesion. Neurological examination was normal, with no history of seizures or focal deficits. Brain MRI revealed ipsilateral cutaneous, subcutaneous, muscular, and osseous atrophy, as well as atrophy of the left parotid and submandibular glands. Additionally, subcortical white matter lesions were identified in the left frontal lobe in the absence of hemispheric cerebral atrophy. Conclusions: This case highlights a significant radioclinical dissociation, demonstrating that central nervous system involvement may occur even in clinically stable and paucisymptomatic forms of PRS. This disease may be associated with subclinical intracranial abnormalities, underscoring the need for systematic neuroimaging evaluation even in the absence of neurological manifestations. Based on the available literature and the specific features of the present case, we propose a practical clinical framework and imaging algorithm to facilitate early diagnosis and to contribute to the standardization of the diagnostic approach in this rare disorder. Full article
(This article belongs to the Special Issue Neurological Disorders: Diagnosis and Management)
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15 pages, 1479 KB  
Article
Choice of Treatment Modality and Validity of Direct Surgery for Complex Posterior Inferior Cerebellar Artery-Related Aneurysms
by Fumihiro Hamada, Hitoshi Fukuda, Naoki Fukui, Yusuke Ueba, Motonobu Nonaka, Mitsuhiro Takemura, Namito Kida and Tetsuya Ueba
J. Clin. Med. 2025, 14(23), 8270; https://doi.org/10.3390/jcm14238270 - 21 Nov 2025
Viewed by 811
Abstract
Background/Objectives: Complex aneurysms of the posterior inferior cerebellar artery (PICA) remain challenging because of their deep location, variable morphology, and proximity to critical neurovascular structures. Although endovascular therapy is preferred, its feasibility is limited in wide-necked, fusiform, or dissecting lesions. We describe our [...] Read more.
Background/Objectives: Complex aneurysms of the posterior inferior cerebellar artery (PICA) remain challenging because of their deep location, variable morphology, and proximity to critical neurovascular structures. Although endovascular therapy is preferred, its feasibility is limited in wide-necked, fusiform, or dissecting lesions. We describe our tertiary referral hospital single-center experience with tailored microsurgical and endovascular strategies—emphasizing occipital artery–PICA (OA-PICA) bypass, transcondylar fossa craniotomy, and cerebellomedullary fissure opening—and analyze perioperative factors that influence outcome. Methods: All consecutive patients treated for PICA origin or distal-PICA aneurysms between January 2021 and April 2025 were retrospectively reviewed. Demographics, aneurysm characteristics, procedure type, antithrombotic regimen, complications, diffusion-weighted MRI findings, and 3-month modified Rankin Scale scores were collected. Results: Twelve aneurysms (mean age 61.4 ± 15.2 years; 8 women) were treated: trapping + OA-PICA bypass in 5, direct clipping in 2, flow diverter in 1, endovascular parent artery occlusion in 2, coil embolization in 1, and a hybrid bypass-plus-coil strategy in 1. Two cases were ruptured aneurysms. Perioperative aspirin was used in 2/5 bypass cases; heparin was added in one hybrid case. Asymptomatic PICA-territory infarcts occurred in the three bypasses performed without antiplatelet therapy (one with intra-anastomotic thrombus). No leaks or subcutaneous collections of cerebrospinal fluid were encountered, and no graft occlusions were observed. At 3 months, 9/12 patients achieved a good outcome (mRS 0–2); among them, only one patient with subarachnoid hemorrhage (SAH) experienced postoperative worsening of the mRS. Two cranial nerve palsies (one permanent, one transient) and one wound site hematoma (heparin-associated) resolved without sequelae. Conclusions: Meticulous operative planning allows safe treatment of complex PICA aneurysms. Perioperative aspirin appears beneficial for OA-PICA bypass, whereas perioperative heparin increases bleeding risk. Individualized selection of endovascular, microsurgical, or combined strategies yields favorable early neurological outcomes in this demanding subset of cerebrovascular disease. Full article
(This article belongs to the Special Issue Advances in the Management of Intracranial Aneurysms)
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15 pages, 2862 KB  
Article
Deep Learning-Based Prediction Model of Surgical Indication of Nasal Bone Fracture Using Waters’ View
by Dong Yun Lee, Soo A Lim and Su Rak Eo
Diagnostics 2025, 15(18), 2386; https://doi.org/10.3390/diagnostics15182386 - 19 Sep 2025
Cited by 1 | Viewed by 2359
Abstract
Background/Objectives: The nasal bone is critical to both the functional integrity and esthetic contour of the facial skeleton. Nasal bone fractures constitute the most prevalent facial fracture presentation in emergency departments. The identification of these fractures and the determination of immediate intervention requirements [...] Read more.
Background/Objectives: The nasal bone is critical to both the functional integrity and esthetic contour of the facial skeleton. Nasal bone fractures constitute the most prevalent facial fracture presentation in emergency departments. The identification of these fractures and the determination of immediate intervention requirements pose significant challenges for inexperienced residents, potentially leading to oversight. Methods: A retrospective analysis was conducted on facial trauma patients undergoing cranial radiography (Waters’ view) during initial emergency department assessment between March 2008 and July 2022. This study incorporated 2099 radiographic images. Surgical indications comprised the displacement angle, interosseous gap size, soft tissue swelling thickness, and subcutaneous emphysema. A deep learning-based artificial intelligence (AI) algorithm was designed, trained, and validated for fracture detection on radiographic images. Model performance was quantified through accuracy, precision, recall, and F1 score. Hyperparameters included the batch size (20), epochs (70), 50-layer network architecture, Adam optimizer, and initial learning rate (0.001). Results: The deep learning AI model employing segmentation labeling demonstrated 97.68% accuracy, 82.2% precision, 88.9% recall, and an 85.4% F1 score in nasal bone fracture identification. These outcomes informed the development of a predictive algorithm for guiding conservative versus surgical management decisions. Conclusions: The proposed AI-driven algorithm and criteria exhibit high diagnostic accuracy and operational efficiency in both detecting nasal bone fractures and predicting surgical indications, establishing its utility as a clinical decision-support tool in emergency settings. Full article
(This article belongs to the Special Issue Advances in Plastic Surgery: Diagnosis, Management and Prognosis)
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22 pages, 4851 KB  
Article
Porous Hydrogels Prepared by Two-Step Gelation Method for Bone Regeneration
by Yongzhi Li, Jiangshan Liu, Jiawei Wei, Li Yuan, Jiaxin Hu, Siluo Dai, Yubao Li and Jidong Li
J. Funct. Biomater. 2025, 16(3), 100; https://doi.org/10.3390/jfb16030100 - 13 Mar 2025
Cited by 9 | Viewed by 4065
Abstract
Hierarchical porous hydrogels possess advantageous characteristics that facilitate cell adhesion, promote tissue growth, and enhance angiogenesis and osteogenesis. In this study, porous composite hydrogels were successfully prepared by a two-step gelation method with sodium alginate (SA), gelatin (GEL), and calcium hydrogen phosphate (DCP) [...] Read more.
Hierarchical porous hydrogels possess advantageous characteristics that facilitate cell adhesion, promote tissue growth, and enhance angiogenesis and osteogenesis. In this study, porous composite hydrogels were successfully prepared by a two-step gelation method with sodium alginate (SA), gelatin (GEL), and calcium hydrogen phosphate (DCP) as the main components. The fabricated porous hydrogels initially featured small pores (approximately 60 μm), and gradually evolved to large pores (exceeding 250 μm) during the gradual degradation in the cellular microenvironment. In vitro cell culture experiments indicated that these hydrogels could enhance the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells due to the hierarchical porous structure and the incorporation of DCP. Subcutaneous implantation and cranial defect repair experiments in Sprague−Dawley rats further confirmed that the small initial pore size of hydrogel scaffolds can provide more sites for cell adhesion. Additionally, the gradual degradation to form large pores was conducive to cell/tissue growth and blood vessel formation, ultimately being beneficial for vascularized bone regeneration. In summary, this study proposes an innovative strategy for developing porous hydrogels with gradual degradation for functional bone regeneration. Full article
(This article belongs to the Section Bone Biomaterials)
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16 pages, 2336 KB  
Systematic Review
Proprioceptive Neuromuscular Facilitation and/or Electrical Stimulation in Patients with Peripheral Facial Paralysis: A Systematic Review
by Nerea Dominguez-Defez, Juan Lopez-Barreiro, Pablo Hernandez-Lucas and Ana González-Castro
Neurol. Int. 2025, 17(2), 17; https://doi.org/10.3390/neurolint17020017 - 23 Jan 2025
Cited by 8 | Viewed by 12979
Abstract
Background: Peripheral facial paralysis (PFP) affects the facial nerve, the seventh cranial nerve. It has an incidence rate of 20–30 cases per 100,000 habitants. The diagnosis is clinical, though imaging tests may be required in some cases. The treatment protocol includes medication, physiotherapy, [...] Read more.
Background: Peripheral facial paralysis (PFP) affects the facial nerve, the seventh cranial nerve. It has an incidence rate of 20–30 cases per 100,000 habitants. The diagnosis is clinical, though imaging tests may be required in some cases. The treatment protocol includes medication, physiotherapy, and, in certain cases, surgery. Proprioceptive neuromuscular facilitation (PNF) techniques and electrical stimulation have been shown to be significant for recovery. Although PFP has a high recovery rate, up to 40% of patients may experience permanent sequelae. Objective: to assess the efficacy of treatment based on electrical stimulation and/or PNF in patients affected by PFP. Methods: A systematic search was conducted across six databases (PubMed, Medline, SportDiscus, CINAHL, Scopus, and Web of Science) in November 2024. Randomized controlled trials were included. Results: Fourteen articles were analyzed, applying PNF and/or electrical stimulation methods, pharmacological treatment, low-level laser treatment, subcutaneous collagen injections, and physiotherapy protocols involving facial expression exercises, yielding evidence for the variables assessed. Conclusions: PNF and/or electrical stimulation treatment in patients with PFP can be effective when employed early with appropriate parameters, showing promising results in improving quality of life, facial movement quality, and CMAP and reducing both the incidence and degree of synkinesis. Full article
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16 pages, 3130 KB  
Article
Semi-Automated Recording of Facial Sensitivity in Rat Demonstrates Antinociceptive Effects of the Anti-CGRP Antibody Fremanezumab
by Nicola Benedicter, Karl Messlinger, Birgit Vogler, Kimberly D. Mackenzie, Jennifer Stratton, Nadine Friedrich and Mária Dux
Neurol. Int. 2023, 15(2), 622-637; https://doi.org/10.3390/neurolint15020039 - 29 Apr 2023
Cited by 7 | Viewed by 3810
Abstract
Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically [...] Read more.
Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically used in chronic and episodic migraines, can modify facial sensitivity recorded by a semi-automatic system. Rats of both sexes primed to drink from a sweet source had to pass a noxious mechanical or heat barrier to reach the source. Under these experimental conditions, animals of all groups tended to drink longer and more when they had received a subcutaneous injection of 30 mg/kg fremanezumab compared to control animals injected with an isotype control antibody 12–13 days prior to testing, but this was significant only for females. In conclusion, anti-CGRP antibody, fremanezumab, reduces facial sensitivity to noxious mechanical and thermal stimulation for more than one week, especially in female rats. Anti-CGRP antibodies may reduce not only headache but also cranial sensitivity in migraineurs. Full article
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10 pages, 890 KB  
Article
Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV
by Simone Parisi, Maria Chiara Ditto, Rossella Talotta, Angela Laganà, Clara Lisa Peroni and Enrico Fusaro
J. Pers. Med. 2023, 13(4), 620; https://doi.org/10.3390/jpm13040620 - 31 Mar 2023
Viewed by 1896
Abstract
Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at [...] Read more.
Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital “Città della Salute e della Scienza” in Turin were monitored every 6–7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8–1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1–5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits. Full article
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26 pages, 19785 KB  
Article
Bone Formation on Murine Cranial Bone by Injectable Cross-Linked Hyaluronic Acid Containing Nano-Hydroxyapatite and Bone Morphogenetic Protein
by Yuki Hachinohe, Masayuki Taira, Miki Hoshi, Wataru Hatakeyama, Tomofumi Sawada and Hisatomo Kondo
Polymers 2022, 14(24), 5368; https://doi.org/10.3390/polym14245368 - 8 Dec 2022
Cited by 7 | Viewed by 3227
Abstract
New injection-type bone-forming materials are desired in dental implantology. In this study, we added nano-hydroxyapatite (nHAp) and bone morphogenetic protein (BMP) to cross-linkable thiol-modified hyaluronic acid (tHyA) and evaluated its usefulness as an osteoinductive injectable material using an animal model. The sol (ux-tHyA) [...] Read more.
New injection-type bone-forming materials are desired in dental implantology. In this study, we added nano-hydroxyapatite (nHAp) and bone morphogenetic protein (BMP) to cross-linkable thiol-modified hyaluronic acid (tHyA) and evaluated its usefulness as an osteoinductive injectable material using an animal model. The sol (ux-tHyA) was changed to a gel (x-tHyA) by mixing with a cross-linker. We prepared two sol–gel (SG) material series, that is, x-tHyA + BMP with and without nHAp (SG I) and x-tHyA + nHAp with and without BMP (SG II). SG I materials in the sol stage were injected into the cranial subcutaneous connective tissues of mice, followed by in vivo gelation, while SG II materials gelled in Teflon rings were surgically placed directly on the cranial bones of rats. The animals were sacrificed 8 weeks after implantation, followed by X-ray analysis and histological examination. The results revealed that bone formation occurred at a high rate (>70%), mainly as ectopic bone in the SG I tests in mouse cranial connective tissues, and largely as bone augmentation in rat cranial bones in the SG II experiments when x-tHyA contained both nHAp and BMP. The prepared x-tHyA + nHAp + BMP SG material can be used as an injection-type osteoinductive bone-forming material. Sub-periosteum injection was expected. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering and Regeneration)
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7 pages, 1652 KB  
Case Report
Recurrent Metastatic Chordoma to the Liver: A Case Report and Review of the Literature
by Thomas E. Dickerson, Asad Ullah, Sathvik Saineni, Sandresh Sultan, Srikar Sama, Intisar Ghleilib, Nikhil G. Patel, Islam A. Elhelf and Nagla Abdel Karim
Curr. Oncol. 2022, 29(7), 4625-4631; https://doi.org/10.3390/curroncol29070367 - 30 Jun 2022
Cited by 5 | Viewed by 4493
Abstract
Chordoma is a rare malignant neoplasm derived from notochordal tissue that primarily affects the axial skeleton. Almost 40% of patients have non-cranial chordoma metastases. The most common metastatic sites are the lungs, bones, lymph nodes, and subcutaneous tissue. We present a 52-year female [...] Read more.
Chordoma is a rare malignant neoplasm derived from notochordal tissue that primarily affects the axial skeleton. Almost 40% of patients have non-cranial chordoma metastases. The most common metastatic sites are the lungs, bones, lymph nodes, and subcutaneous tissue. We present a 52-year female with a history of sacral chordoma presenting with abdominal fullness, early satiety, and a palpable abdominal mass. Abdominal magnetic resonance imaging (MRI) revealed an isolated, highly vascularized, and multilobed liver mass in the left lateral segment. The mass was surgically removed using a clean surgical margin. A histological examination and immunohistochemical staining were consistent with a metastatic chordoma. Two years later, follow-up imaging studies showed a 6.5 × 4.0 × 2.0 cm right liver lesion with multiple lungs, chest wall, pleural, and diaphragmatic lesions. Microscopic- and immunohistochemical staining revealed a recurrent metastatic chordoma. Herein, we present a unique case of metastatic recurrent chordoma in the liver with the involvement of other sites. To the best of our knowledge, no other case of recurrent liver metastasis has been reported. Full article
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27 pages, 10058 KB  
Article
Scaffold Pore Curvature Influences ΜSC Fate through Differential Cellular Organization and YAP/TAZ Activity
by W. Benton Swanson, Maiko Omi, Seth M. Woodbury, Lindsey M. Douglas, Miranda Eberle, Peter X. Ma, Nan E. Hatch and Yuji Mishina
Int. J. Mol. Sci. 2022, 23(9), 4499; https://doi.org/10.3390/ijms23094499 - 19 Apr 2022
Cited by 47 | Viewed by 6519
Abstract
Tissue engineering aims to repair, restore, and/or replace tissues in the human body as an alternative to grafts and prostheses. Biomaterial scaffolds can be utilized to provide a three-dimensional microenvironment to facilitate tissue regeneration. Previously, we reported that scaffold pore size influences vascularization [...] Read more.
Tissue engineering aims to repair, restore, and/or replace tissues in the human body as an alternative to grafts and prostheses. Biomaterial scaffolds can be utilized to provide a three-dimensional microenvironment to facilitate tissue regeneration. Previously, we reported that scaffold pore size influences vascularization and extracellular matrix composition both in vivo and in vitro, to ultimately influence tissue phenotype for regenerating cranial suture and bone tissues, which have markedly different tissue properties despite similar multipotent stem cell populations. To rationally design biomaterials for specific cell and tissue fate specification, it is critical to understand the molecular processes governed by cell-biomaterial interactions, which guide cell fate specification. Building on our previous work, in this report we investigated the hypothesis that scaffold pore curvature, the direct consequence of pore size, modulates the differentiation trajectory of mesenchymal stem cells (MSCs) through alterations in the cytoskeleton. First, we demonstrated that sufficiently small pores facilitate cell clustering in subcutaneous explants cultured in vivo, which we previously reported to demonstrate stem tissue phenotype both in vivo and in vitro. Based on this observation, we cultured cell-scaffold constructs in vitro to assess early time point interactions between cells and the matrix as a function of pore size. We demonstrate that principle curvature directly influences nuclear aspect and cell aggregation in vitro. Scaffold pores with a sufficiently low degree of principle curvature enables cell differentiation; pharmacologic inhibition of actin cytoskeleton polymerization in these scaffolds decreased differentiation, indicating a critical role of the cytoskeleton in transducing cues from the scaffold pore microenvironment to the cell nucleus. We fabricated a macropore model, which allows for three-dimensional confocal imaging and demonstrates that a higher principle curvature facilitates cell aggregation and the formation of a potentially protective niche within scaffold macropores which prevents MSC differentiation and retains their stemness. Sufficiently high principle curvature upregulates yes-associated protein (YAP) phosphorylation while decreased principle curvature downregulates YAP phosphorylation and increases YAP nuclear translocation with subsequent transcriptional activation towards an osteogenic differentiation fate. Finally, we demonstrate that the inhibition of the YAP/TAZ pathway causes a defect in differentiation, while YAP/TAZ activation causes premature differentiation in a curvature-dependent way when modulated by verteporfin (VP) and 1-oleyl-lysophosphatidic acid (LPA), respectively, confirming the critical role of biomaterials-mediated YAP/TAZ signaling in cell differentiation and fate specification. Our data support that the principle curvature of scaffold macropores is a critical design criterion which guides the differentiation trajectory of mesenchymal stem cells’ scaffolds. Biomaterial-mediated regulation of YAP/TAZ may significantly contribute to influencing the regenerative outcomes of biomaterials-based tissue engineering strategies through their specific pore design. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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17 pages, 3909 KB  
Case Report
Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients
by Teresa Esposito, Carla Schettino, Paola Polverino, Salvatore Allocca, Laura Adelfi, Alessandra D’Amico, Guglielmo Capaldo, Bruno Varriale, Anna Di Salle, Gianfranco Peluso, Giuseppe Sorrentino, Giacomo Lus, Simone Sampaolo, Giuseppe Di Iorio and Mariarosa Anna Beatrice Melone
Nutrients 2017, 9(7), 783; https://doi.org/10.3390/nu9070783 - 21 Jul 2017
Cited by 31 | Viewed by 31053
Abstract
Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact [...] Read more.
Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact with several molecular targets implicated in carcinogenesis. Here, we describe the impact of different dietary patterns, namely Mediterranean diet (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin, on NF1 patients’ health. After six months, patients adopting a traditional MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a significant reduction in the number and volume of cutaneous neurofibromas; these results were confirmed in subsequent evaluations. Notably, in one patient, a large cranial plexiform neurofibroma exhibited a reduction in volume (28%) confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet nor WesDiet enriched with curcumin exhibited any significant positive effect. We hypothesize that the combination of a polyphenol-rich Mediterranean diet and curcumin was responsible for the beneficial effect observed on NF1. This is, to the best of our knowledge, the first experience with curcumin supplementation in NF1 patients. Our report suggests that an integrated nutritional approach may effectively aid in the management of NF1. Full article
(This article belongs to the Special Issue Effects of Polyphenol-Rich Foods on Human Health)
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11 pages, 3363 KB  
Article
Effects of PMMA and Cross-Linked Dextran Filler for Soft Tissue Augmentation in Rats
by Jung-Bo Huh, Joo-Hyun Kim, Soyun Kim, So-Hyoun Lee, Kyung Mi Shim, Se Eun Kim, Seong Soo Kang and Chang-Mo Jeong
Int. J. Mol. Sci. 2015, 16(12), 28523-28533; https://doi.org/10.3390/ijms161226112 - 1 Dec 2015
Cited by 7 | Viewed by 10445
Abstract
This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered [...] Read more.
This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered in the negative and positive control groups, and DiHM and PDiHM were administered in the test groups (n = 10 in each group). The site of cranial subcutaneous injection was the mid-point of the interpupillary line, and the site of intraoral submucosal injection was the ridge crest 2 mm below the cervical line of the mandibular left incisor. Before and immediately after filler injection, intraoral photos and lateral cephalometric radiographs were taken for analysis and comparison of the effect of the filler on the injection sites. The filler injected areas were converted into sequential size changes (%) of the baseline. Histomorphologic examination was performed after 12 weeks. The smallest value in the filler injected area was observed during the experimental period in the normal saline group (p < 0.001), which was almost absorbed at 4 weeks (7.19% ± 12.72%). The HA group exhibited a steady decrease in sequential size and showed a lower value than the DiHM and PDiHM groups (saline < HA < DHiM, PDHiM, p < 0.001). DiHM and PDiHM tended to increase for the first 4 weeks and later decreased until 12 weeks. In this study on DiHM and PDiHM, there was no histological abnormality in cranial skin and oral mucosa. DiHM and PDiHM filler materials with injection system provide an excellent alternative surgical method for use in oral and craniofacial fields. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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