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1.
Zool Res ; 42(5): 650-659, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34472226

RESUMO

Phosphatidylserine (PS) is distributed asymmetrically in the plasma membrane of eukaryotic cells. Phosphatidylserine flippase (P4-ATPase) transports PS from the outer leaflet of the lipid bilayer to the inner leaflet of the membrane to maintain PS asymmetry. The ß subunit TMEM30A is indispensable for transport and proper function of P4-ATPase. Previous studies have shown that the ATP11A and TMEM30A complex is the molecular switch for myotube formation. However, the role of Tmem30a in skeletal muscle regeneration remains elusive. In the current study, Tmem30a was highly expressed in the tibialis anterior (TA) muscles of dystrophin-null ( mdx) mice and BaCl 2-induced muscle injury model mice. We generated a satellite cell (SC)-specific Tmem30a conditional knockout (cKO) mouse model to investigate the role of Tmem30a in skeletal muscle regeneration. The regenerative ability of cKO mice was evaluated by analyzing the number and diameter of regenerated SCs after the TA muscles were injured by BaCl 2-injection. Compared to the control mice, the cKO mice showed decreased Pax7 + and MYH3 + SCs, indicating diminished SC proliferation, and decreased expression of muscular regulatory factors (MYOD and MYOG), suggesting impaired myoblast proliferation in skeletal muscle regeneration. Taken together, these results demonstrate the essential role of Tmem30a in skeletal muscle regeneration.


Assuntos
Proteínas de Membrana/metabolismo , Músculo Esquelético/fisiologia , Regeneração/fisiologia , Células Satélites de Músculo Esquelético/metabolismo , Animais , Proliferação de Células , Distrofina/genética , Distrofina/metabolismo , Antagonistas de Estrogênios/toxicidade , Regulação da Expressão Gênica/fisiologia , Genótipo , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos mdx , Camundongos Knockout , Músculo Esquelético/efeitos dos fármacos , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Fator de Transcrição PAX7/genética , Fator de Transcrição PAX7/metabolismo , Regeneração/genética , Tamoxifeno/toxicidade
3.
Nat Commun ; 12(1): 4767, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362912

RESUMO

Axons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.


Assuntos
Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Bainha de Mielina/fisiologia , Neurônios/fisiologia , Regeneração/fisiologia , Animais , Axônios/fisiologia , Feminino , Interneurônios/fisiologia , Masculino , Camundongos , Oligodendroglia , Organogênese/fisiologia , Parvalbuminas , Córtex Somatossensorial
4.
Sheng Li Xue Bao ; 73(4): 577-583, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34405214

RESUMO

The objective of this study was to explore the roles of arachidonic acid cytochrome P450ω hydroxylase CYP4A14 in skeletal muscle regeneration after injury. Wild-type (WT) control mice and Cyp4a14 knockout (A14-/-) mice were used to establish the muscle injury and regeneration model by intramuscular injection with cardiotoxin (CTX) on the tibial anterior (TA) muscle. The TA muscles were harvested at the time points of 0, 3, 5 and 15 days after injury. The changes in skeletal muscle regeneration and fibrosis were assessed by wheat germ agglutinin (WGA) staining and Sirius Red staining. Immunohistochemical staining was used to observe the expression of proliferation-related protein Ki-67 and macrophage marker protein Mac-2. The mRNA levels of regeneration and inflammation associated genes were analyzed by real-time PCR. The results showed that the cross-section area (CSA) of regenerated myofibers in A14-/- mice was significantly smaller (P < 0.05), while the percentage of fibrosis area was significantly higher than those in WT mice at 15 days after injury (P < 0.05). In A14-/- muscles, both the ratio of Ki-67 positive proliferating cells and the mRNA levels of differentiation associated genes Myod1 and Myog were significantly lower than those in WT muscles (P < 0.05). At 3 days after injury, the mRNA expression of inflammatory cells marker genes CD45 and CD11b and Mac-2 positive macrophages in A14-/- muscles were significantly lower than those in WT skeletal muscle (P < 0.05). Macrophages derived pro-regeneration cytokines IL-1ß, IGF-1 and SDF-1 were also significantly decreased in A14-/- muscles (P < 0.05). These results suggest that arachidonic acid cytochrome P450ω hydroxylase CYP4A14 plays a critical role in skeletal muscle regeneration after injury.


Assuntos
Oxigenases de Função Mista , Regeneração , Animais , Ácido Araquidônico , Citocromos , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético
5.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360604

RESUMO

The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.


Assuntos
Matriz Extracelular/química , Desenvolvimento Musculoesquelético , Doenças Musculoesqueléticas/terapia , Impressão Tridimensional/instrumentação , Regeneração , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Bioimpressão/métodos , Humanos
6.
Nat Commun ; 12(1): 4808, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376683

RESUMO

Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart.


Assuntos
MicroRNAs/genética , Infarto do Miocárdio/genética , Miócitos Cardíacos/metabolismo , Regeneração/genética , Animais , Animais Recém-Nascidos , Cardiomegalia/genética , Células Cultivadas , Ecocardiografia , Regulação da Expressão Gênica , Humanos , Hiperplasia/genética , Camundongos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
Nat Biomed Eng ; 5(8): 880-896, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34426676

RESUMO

Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types using the microRNA mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells to the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.


Assuntos
Células Endoteliais/transplante , Coração/fisiologia , Infarto do Miocárdio/terapia , Miócitos de Músculo Liso/transplante , Regeneração , Animais , Ácido Ascórbico/farmacologia , Proteína Morfogenética Óssea 4/farmacologia , Reprogramação Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Junções Comunicantes/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Neovascularização Fisiológica , Transcriptoma
8.
Viruses ; 13(8)2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34452517

RESUMO

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.


Assuntos
COVID-19/virologia , Células Quimiorreceptoras/virologia , Mucosa Olfatória/virologia , SARS-CoV-2 , Órgão Vomeronasal/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/patologia , Células Quimiorreceptoras/patologia , Masculino , Mesocricetus , Cavidade Nasal/patologia , Cavidade Nasal/virologia , Mucosa Olfatória/metabolismo , Mucosa Olfatória/patologia , Neurônios Receptores Olfatórios/metabolismo , Neurônios Receptores Olfatórios/patologia , Neurônios Receptores Olfatórios/virologia , Receptores de Coronavírus/metabolismo , Regeneração , SARS-CoV-2/isolamento & purificação , Órgão Vomeronasal/metabolismo , Órgão Vomeronasal/patologia
9.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360970

RESUMO

Anterior cruciate ligament (ACL) ruptures are usually treated with autograft implantation to prevent knee instability. Tissue engineered ACL reconstruction is becoming promising to circumvent autograft limitations. The aim was to evaluate the influence of cyclic stretch on lapine (L) ACL fibroblasts on embroidered scaffolds with respect to adhesion, DNA and sulphated glycosaminoglycan (sGAG) contents, gene expression of ligament-associated extracellular matrix genes, such as type I collagen, decorin, tenascin C, tenomodulin, gap junctional connexin 43 and the transcription factor Mohawk. Control scaffolds and those functionalized by gas phase fluorination and cross-linked collagen foam were either pre-cultured with a suspension or with spheroids of LACL cells before being subjected to cyclic stretch (4%, 0.11 Hz, 3 days). Stretch increased significantly the scaffold area colonized with cells but impaired sGAGs and decorin gene expression (functionalized scaffolds seeded with cell suspension). Stretching increased tenascin C, connexin 43 and Mohawk but decreased decorin gene expression (control scaffolds seeded with cell suspension). Pre-cultivation of functionalized scaffolds with spheroids might be the more suitable method for maintaining ligamentogenesis in 3D scaffolds compared to using a cell suspension due to a significantly higher sGAG content in response to stretching and type I collagen gene expression in functionalized scaffolds.


Assuntos
Ligamento Cruzado Anterior/fisiologia , Esferoides Celulares/citologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Ligamento Cruzado Anterior/citologia , Adesão Celular , Proliferação de Células , Células Cultivadas , Conexinas/genética , Conexinas/metabolismo , Decorina/genética , Decorina/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Fibroblastos/fisiologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Homeostase , Masculino , Poliésteres/química , Coelhos , Regeneração , Esferoides Celulares/metabolismo , Estresse Mecânico
10.
Theranostics ; 11(16): 7879-7895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335970

RESUMO

Rationale: Previous studies have shown that human embryonic stem cell-derived cardiomyocytes improved myocardial recovery when administered to infarcted pig and non-human primate hearts. However, the engraftment of intramyocardially delivered cells is poor and the effectiveness of clinically relevant doses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in large animal models of myocardial injury remains unknown. Here, we determined whether thymosin ß4 (Tb4) could improve the engraftment and reparative potency of transplanted hiPSC-CMs in a porcine model of myocardial infarction (MI). Methods: Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro. After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 108 hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs. Myocardial recovery was assessed by cardiac magnetic resonance imaging (MRI), arrhythmogenesis was monitored with implanted loop recorders, and tumorigenesis was evaluated via whole-body MRI. Results: In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation. In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size. hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs. Conclusions: Co-treatment with Tb4-microspheres and hiPSC-CMs was safe and enhanced the reparative potency of hiPSC-CMs for myocardial repair in a large-animal model of MI.


Assuntos
Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Timosina/farmacologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , China , Modelos Animais de Doenças , Células Endoteliais/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/patologia , Regeneração , Transplante de Células-Tronco/métodos , Suínos , Timosina/metabolismo , Timosina/fisiologia
11.
Front Immunol ; 12: 707856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335621

RESUMO

Several infectious pathologies in humans, such as tuberculosis or SARS-CoV-2, are responsible for tissue or lung damage, requiring regeneration. The regenerative capacity of adult mammals is limited to few organs. Critical injuries of non-regenerative organs trigger a repair process that leads to a definitive architectural and functional disruption, while superficial wounds result in scar formation. Tissue lesions in mammals, commonly studied under non-infectious conditions, trigger cell death at the site of the injury, as well as the production of danger signals favouring the massive recruitment of immune cells, particularly macrophages. Macrophages are also of paramount importance in infected injuries, characterized by the presence of pathogenic microorganisms, where they must respond to both infection and tissue damage. In this review, we compare the processes implicated in the tissue repair of non-infected versus infected injuries of two organs, the skeletal muscles and the lungs, focusing on the primary role of macrophages. We discuss also the negative impact of infection on the macrophage responses and the possible routes of investigation for new regenerative therapies to improve the recovery state as seen with COVID-19 patients.


Assuntos
COVID-19/imunologia , Macrófagos Alveolares/fisiologia , SARS-CoV-2/fisiologia , Remodelação das Vias Aéreas , Animais , Humanos , Infecções , Mamíferos , Regeneração , Cicatrização
12.
Int J Mol Sci ; 22(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34360689

RESUMO

Macrophages were first described as phagocytic immune cells responsible for maintaining tissue homeostasis by the removal of pathogens that disturb normal function. Historically, macrophages have been viewed as terminally differentiated monocyte-derived cells that originated through hematopoiesis and infiltrated multiple tissues in the presence of inflammation or during turnover in normal homeostasis. However, improved cell detection and fate-mapping strategies have elucidated the various lineages of tissue-resident macrophages, which can derive from embryonic origins independent of hematopoiesis and monocyte infiltration. The role of resident macrophages in organs such as the skin, liver, and the lungs have been well characterized, revealing functions well beyond a pure phagocytic and immunological role. In the heart, recent research has begun to decipher the functional roles of various tissue-resident macrophage populations through fate mapping and genetic depletion studies. Several of these studies have elucidated the novel and unexpected roles of cardiac-resident macrophages in homeostasis, including maintaining mitochondrial function, facilitating cardiac conduction, coronary development, and lymphangiogenesis, among others. Additionally, following cardiac injury, cardiac-resident macrophages adopt diverse functions such as the clearance of necrotic and apoptotic cells and debris, a reduction in the inflammatory monocyte infiltration, promotion of angiogenesis, amelioration of inflammation, and hypertrophy in the remaining myocardium, overall limiting damage extension. The present review discusses the origin, development, characterization, and function of cardiac macrophages in homeostasis, cardiac regeneration, and after cardiac injury or stress.


Assuntos
Coração/fisiologia , Homeostase , Macrófagos/fisiologia , Regeneração , Animais , Humanos , Inflamação , Macrófagos/imunologia , Miocárdio/imunologia
13.
Curr Cardiol Rep ; 23(10): 146, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34410521

RESUMO

PURPOSE OF REVIEW: Heart failure remains a major public health concern with high burden of morbidity and mortality despite advances in pharmacotherapy, device therapy, and surgical and percutaneous techniques. Cardiac regeneration may have a role to play in these patients with a huge unmet need for these therapies in patients with chronic ischemic heart disease, post-infarct heart failure, dilated cardiomyopathy, and heart failure with preserved ejection fraction. RECENT FINDINGS: In this review, we focus on the pre-clinical and translational basis for different modes of cardiac regenerative medicine and then critically appraise the clinical evidence amassed from pivotal clinical trials focused on cardiac regeneration for ischemic and non-ischemic cardiomyopathies. Cardiac regenerative medicine is rapidly evolving with novel approaches involving cell-based, cell-free, tissue engineering, and hybrid therapies to achieve myocardial regeneration and repair. Further studies are warranted with a robust comparison arm with optimal contemporary medical therapy to translate regenerative therapies to a clinical reality.


Assuntos
Insuficiência Cardíaca , Isquemia Miocárdica , Coração , Insuficiência Cardíaca/terapia , Humanos , Isquemia Miocárdica/terapia , Regeneração , Medicina Regenerativa , Transplante de Células-Tronco
14.
FASEB J ; 35(9): e21816, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34396583

RESUMO

Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.


Assuntos
Diferenciação Celular/fisiologia , Epitélio/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Mucosa Respiratória/metabolismo , Células-Tronco/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Proliferação de Células/fisiologia , Células Epiteliais/metabolismo , Feminino , Homeostase/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração/fisiologia , Transdução de Sinais/fisiologia , Traqueia/metabolismo
15.
Trials ; 22(1): 436, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229752

RESUMO

BACKGROUND: Dental pulp necrosis, a common health problem, is traditionally treated with root canal therapy; however, it fails in restoring the vitality of damaged pulp. Most studies regarding regenerative endodontic therapy (RET) are limited to the treatment of immature necrotic teeth. Given that injectable platelet-rich fibrin (i-PRF) has shown great potential in regenerative medicine as a novel platelet concentration, this study is designed to explore whether i-PRF can serve as a biological scaffold, extending the indications for RET and improving the clinical feasibility of RET in mature permanent teeth with pulp necrosis. METHODS: This is a randomised, double-blind, controlled, multicentre clinical trial designed to evaluate the clinical feasibility of RET for mature permanent teeth with pulp necrosis and to compare the efficacy of i-PRF and blood clots as scaffolds in RET. A total of 346 patients will be recruited from three centres and randomised at an allocation ratio of 1:1 to receive RET with either a blood clot or i-PRF. The changes in subjective symptoms, clinical examinations, and imaging examinations will be tracked longitudinally for a period of 24 months. The primary outcome is the success rate of RET after 24 months. The secondary outcome is the change in pulp vitality measured via thermal and electric pulp tests. In addition, the incidence of adverse events such as discolouration, reinfection, and root resorption will be recorded for a safety evaluation. DISCUSSION: This study will evaluate the clinical feasibility of RET in mature permanent teeth with pulp necrosis, providing information regarding the efficacy, benefits, and safety of RET with i-PRF. These results may contribute to changes in the treatment of pulp necrosis in mature permanent teeth and reveal the potential of i-PRF as a novel biological scaffold for RET. TRIAL REGISTRATION: ClinicalTrials.gov NCT04313010 . Registered on 19 March 2020.


Assuntos
Fibrina Rica em Plaquetas , Endodontia Regenerativa , Necrose da Polpa Dentária/diagnóstico por imagem , Necrose da Polpa Dentária/terapia , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Regeneração , Tratamento do Canal Radicular
16.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204292

RESUMO

Skin injury is quite common, and the wound healing is a complex process involving many types of cells, the extracellular matrix, and soluble mediators. Cell differentiation, migration, and proliferation are essential in restoring the integrity of the injured tissue. Despite the advances in science and technology, we have yet to find the ideal dressing that can support the healing of cutaneous wounds effectively, particularly for difficult-to-heal chronic wounds such as diabetic foot ulcers, bed sores, and venous ulcers. Hence, there is a need to identify and incorporate new ideas and methods to design a more effective dressing that not only can expedite wound healing but also can reduce scarring. Calcium has been identified to influence the wound healing process. This review explores the functions and roles of calcium in skin regeneration and reconstruction during would healing. Furthermore, this review also investigates the possibility of incorporating calcium into scaffolds and examines how it modulates cutaneous wound healing. In summary, the preliminary findings are promising. However, some challenges remain to be addressed before calcium can be used for cutaneous wound healing in clinical settings.


Assuntos
Cálcio/metabolismo , Cicatrização/fisiologia , Animais , Bandagens , Cálcio/farmacologia , Cálcio na Dieta/administração & dosagem , Fibroblastos/metabolismo , Humanos , Queratinócitos/metabolismo , Nanopartículas/química , Neovascularização Fisiológica , Regeneração , Pele/lesões , Pele/metabolismo , Nanomedicina Teranóstica , Engenharia Tecidual , Tecidos Suporte , Cicatrização/efeitos dos fármacos
17.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208633

RESUMO

The clinical application of human platelet lysate (HPL) holds promise for tissue regeneration, and the development of an efficient vehicle for its delivery is desired. Chitosan-based hydrogels are potential candidates, but they often exhibit weak mechanical properties. In this study, a chitosan/gelatin (CS-GE) hydrogel crosslinked by glyoxal was fabricated for sustained release of HPL. The influence of HPL on Hs68 fibroblast and human umbilical vein endothelial cell (HUVEC) culture was evaluated, and we found that supplementing 5% HPL in the medium could significantly improve cell proliferation relative to supplementing 10% fetal bovine serum (FBS). Moreover, HPL accelerated the in vitro wound closure of Hs68 cells and facilitated the tube formation of HUVECs. Subsequently, we fabricated CS-GE hydrogels crosslinked with different concentrations of glyoxal, and the release pattern of FITC-dextrans (4, 40 and 500 kDa) from the hydrogels was assessed. After an ideal glyoxal concentration was determined, we further characterized the crosslinked CS-GE hydrogels encapsulated with different amounts of HPL. The HPL-incorporated hydrogel was shown to significantly promote the proliferation of Hs68 cells and the migration of HUVECs. Moreover, the release pattern of transforming growth factor-ß1 (TGF-ß1) and platelet-derived growth factor-BB (PDGF-BB) from hydrogel was examined in vitro, demonstrating a sustained release profile of the growth factors. Finally, the chick chorioallantoic membrane assay revealed that HPL encapsulation in the hydrogel significantly stimulated angiogenesis in ovo. These results demonstrate the great potential of the crosslinked CS-GE hydrogel to serve as an effective delivery system for HPL to promote tissue regeneration.


Assuntos
Produtos Biológicos/farmacologia , Plaquetas/metabolismo , Quitosana , Gelatina , Glioxal , Hidrogéis , Regeneração/efeitos dos fármacos , Proliferação de Células , Quitosana/química , Dextranos/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Gelatina/química , Glioxal/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Neovascularização Fisiológica , Porosidade , Cicatrização/efeitos dos fármacos
18.
Int J Nanomedicine ; 16: 4289-4319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211272

RESUMO

Recent developments in three-dimensional (3D) printing technology offer immense potential in fabricating scaffolds and implants for various biomedical applications, especially for bone repair and regeneration. As the availability of autologous bone sources and commercial products is limited and surgical methods do not help in complete regeneration, it is necessary to develop alternative approaches for repairing large segmental bone defects. The 3D printing technology can effectively integrate different types of living cells within a 3D construct made up of conventional micro- or nanoscale biomaterials to create an artificial bone graft capable of regenerating the damaged tissues. This article reviews the developments and applications of 3D printing in bone tissue engineering and highlights the numerous conventional biomaterials and nanomaterials that have been used in the production of 3D-printed scaffolds. A comprehensive overview of the 3D printing methods such as stereolithography (SLA), selective laser sintering (SLS), fused deposition modeling (FDM), and ink-jet 3D printing, and their technical and clinical applications in bone repair and regeneration has been provided. The review is expected to be useful for readers to gain an insight into the state-of-the-art of 3D printing of bone substitutes and their translational perspectives.


Assuntos
Materiais Biocompatíveis/química , Substitutos Ósseos , Nanoestruturas/química , Impressão Tridimensional , Engenharia Tecidual/métodos , Ligas/química , Animais , Substitutos Ósseos/química , Osso e Ossos/fisiologia , Humanos , Lasers , Impressão Tridimensional/instrumentação , Regeneração , Estereolitografia , Titânio/química
20.
Eur J Oral Sci ; 129(4): e12790, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34288157

RESUMO

Dental pulp stem cells (DPSCs) are multipotent and may play crucial roles in dentin-pulp regeneration. Recent studies have revealed that long noncoding RNAs (lncRNAs) are implicated in the osteogenic differentiation of DPSCs. However, the specific role and potential mechanisms of the lncRNA trihydroxyacetophenone domain containing nine antisense RNA 1 (THAP9-AS1) during osteogenic differentiation of DPSCs remain unknown. In the present study, we determined that THAP9-AS1 expression was upregulated during osteogenic differentiation of DPSCs. Moreover, we investigated the biological functions of THAP9-AS1 during osteogenic differentiation of DPSCs by loss-of-function assays. THAP9-AS1 knockdown inhibited osteogenic differentiation of DPSCs by decreasing alkaline phosphatase activity, alkaline phosphatase-positive cell ratio, mineralizing matrix and mRNA, and protein levels of early osteogenic-markers. We also found that THAP9-AS1 interacted with miR-652-3p, whose downstream gene target is vascular endothelial growth factor A (VEGFA). In addition, rescue assays indicated that VEGFA rescued the effects of THAP9-AS1 knockdown during osteogenic differentiation of DPSCs. In summary, we verified that knockdown of THAP9-AS1 inhibits osteogenic differentiation of DPSCs via the miR-652-3p/VEGFA axis. Our findings may be helpful to extend research on the mechanisms underlying osteogenic differentiation of DPSCs.


Assuntos
MicroRNAs , RNA Longo não Codificante , Transposases/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Polpa Dentária , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Regeneração , Células-Tronco , Fator A de Crescimento do Endotélio Vascular
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