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1.
Polim Med ; 50(1): 41-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33150750

RESUMO

BACKGROUND: Skin, the first barrier to pathogens, loses its integrity and function after an injury. The presence of an antibacterial dressing at the wound site may prevent bacterial invasion and also improve the healing process. OBJECTIVES: The current study aimed to fabricate a biomimetic membrane with antibacterial properties for healing chronic wounds. MATERIAL AND METHODS: The membranes, fabricated through electrospinning, are comprised of poly(ethylene oxide) (PEO) and zinc oxide nanoparticles (ZnO-NPs) as the main biomaterial and antibacterial agent, respectively. Antibacterial activity, cell attachment and viability were tested to evaluate the biological properties of the membranes. The optimal cell compatible concentration of ZnO-NPs was determined for further studies. In vitro characterization of the membranes was performed to confirm their suitable properties for wound healing. RESULTS: The antibacterial PEO/ZnO-NP membrane containing 2% of nanoparticles showed no cell toxicity, and human fibroblast cells were able to adhere and proliferate on the scaffold. The in vitro results from the tensile test, wettability, porosity, and protein adsorption revealed appropriate properties of the membrane as a scaffold for skin tissue engineering. CONCLUSIONS: Synthetic polymers have been widely used for tissue engineering applications. The proper characteristics of PEO nanofibers, including a high ratio of surface/volume, moderate hydrophilicity and good mechanical properties, make this polymer interesting for skin regeneration. The results demonstrate the potential of the antibacterial PEO/ZnO-NP membrane to be used as an engineered scaffold to improve the wound healing process.


Assuntos
Quitosana , Nanofibras , Polietilenoglicóis , Tecidos Suporte , Óxido de Zinco , Antibacterianos/uso terapêutico , Células Cultivadas , Etilenos , Fibroblastos/citologia , Humanos , Cicatrização
2.
J Med Life ; 13(3): 418-425, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072218

RESUMO

The study aimed to investigate whether a 3D printed beta-tricalcium phosphate (ß-TCP) scaffold tethered with growth factors and fibrin glue implanted autologous bone marrow-derived mesenchymal stem cells would provide a 3D platform for bone regeneration resulting in new bone formation with plasticity. Twenty 3D printed ß-TCP scaffolds, ten scaffolds engrained with osteogenic mesenchymal stem cells with fibrin glue (group A), and ten scaffolds used as a control group with ß-TCP scaffold and fibrin glue inoculation only (group B) were included in the study. Cell infiltration, migration, and proliferation of human osteogenic stem cells on the scaffolds were executed under both static and dynamic culture conditions. Each scaffold was examined post culture after repeated changes in the nutrient medium at 2, 4 or 8 weeks and assessed for opacity and formation of any bone-like tissues macroscopic, radiographic, and microscopic evaluation. Significant changes in all the prerequisite parameters compiled with an evaluated difference of significance showing maxillofacial skeletal repair via tissue engineering by ß-TCP scaffold and MSCs remains will be the most promising alternative to autologous bone grafts and numerous modalities involving a variety of stem cells, growth factors from platelet-rich fibrin.


Assuntos
Fosfatos de Cálcio/farmacologia , Adesivo Tecidual de Fibrina/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Anormalidades Maxilofaciais/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Impressão Tridimensional , Engenharia Tecidual/métodos , Estudos de Casos e Controles , Sobrevivência Celular/efeitos dos fármacos , Humanos , Anormalidades Maxilofaciais/diagnóstico por imagem , Anormalidades Maxilofaciais/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Minerais/análise , Tecidos Suporte/química , Resultado do Tratamento
3.
Cell Prolif ; 53(11): e12917, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33001510

RESUMO

OBJECTIVES: Articular cartilage plays a vital role in bearing and buffering. Injured cartilage and subchondral bone repair is a crucial challenge in cartilage tissue engineering due to the peculiar structure of osteochondral unit and the requirement of osteogenic/chondrogenic bi-directional differentiation. Based on the bionics principle, a nanotextured silk fibroin (SF)-chondroitin sulphate (CS)/hydroxyapatite (HAp) nanowire tough bilayer structure was prepared for osteochondral repair. METHODS: The SF-CS/HAp membrane was constructed by alcohol-induced ß-sheet formation serving as the physical crosslink. Its osteochondral repairing capacity was evaluated by culturing bone marrow mesenchymal stem cells (BMSCs) in vitro and constructing a rat osteochondral defect model in vivo. RESULTS: The bilayer SF-CS/HAp membrane with satisfactory mechanical properties similar to natural cartilage imitated the natural osteochondral unit structural layers and exerted the function of bearing and buffering timely after in vivo implantation. SF-CS layer upregulated the expression of chondrogenesis-related genes of BMSCs by surface nanotopography and sustained release CS. Meanwhile, nanotextured HAp layer assembled with nanowire endowed the membrane with an osteogenic differentiation tendency for BMSCs. In vivo results proved that the biomimetic bilayer structure dramatically promoted new cartilage formation and subchondral bone remodelling for osteochondral defect model after implantation. CONCLUSIONS: The SF-CS/HAp biomimetic bilayer membrane provides a promising strategy for precise osteochondral repair.


Assuntos
Durapatita/química , Fibroínas/química , Células-Tronco Mesenquimais/citologia , Nanoestruturas/química , Tecidos Suporte/química , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Células Cultivadas , Condrogênese , Durapatita/uso terapêutico , Fibroínas/uso terapêutico , Masculino , Nanoestruturas/uso terapêutico , Nanoestruturas/ultraestrutura , Osteogênese , Ratos Sprague-Dawley
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2299-2302, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018467

RESUMO

The fluid dynamics of microporous materials are important to many biomedical processes such as cell deposition in scaffold materials, tissue engineering, and bioreactors. Microporous scaffolds are frequently composed of suspensions of beads that have varying topology which, in turn, informs their hydrodynamic properties. Previous work has shown that shear stress distributions can affect the response of cells in microporous environments. Using computational fluid dynamics, we characterize localized differences in fluid flow attributes such wall shear stress and velocity to better understand the fluid dynamics underpinning microporous device function. We evaluated whether bead packings with similar void fractions had different fluid dynamics as characterized by the distribution of velocity magnitudes and wall shear stress and found that there are differences despite the similarities in void fraction. We show that another metric, the average distance to the nearest wall, can provide an additional variable to measure the porosity and susceptibility of microporous materials to high shear stress. By increasing our understanding of the impact of bead size on cell scaffold fluid dynamics we aim to increase the ability to predict important attributes such as loading efficiency in these devices.


Assuntos
Hidrodinâmica , Tecidos Suporte , Porosidade , Estresse Mecânico , Engenharia Tecidual
5.
Int J Nanomedicine ; 15: 7775-7789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116500

RESUMO

Purpose: Several scaffolds and cell sources are being investigated for cartilage regeneration. The aim of the study was to prepare nanocellulose-based thermosensitive injectable hydrogel scaffolds and assess their potential as 3D scaffolds allowing the chondrogenic differentiation of embedded human dental pulp stem and progenitor cells (hDPSCs). Materials and Methods: The hydrogel-forming solutions were prepared by adding ß-glycerophosphate (GP) to chitosan (CS) at different ratios. Nanocellulose (NC) suspension was produced from hemp hurd then added dropwise to the CS/GP mixture. In vitro characterization of the prepared hydrogels involved optimizing gelation and degradation time, mass-swelling ratio, and rheological properties. The hydrogel with optimal characteristics, NC-CS/GP-21, was selected for further investigation including assessment of biocompatibility. The chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel was investigated in vitro and compared to that of bone marrow-derived mesenchymal stem cells (BMSCs), then was confirmed in vivo in 12 adult Sprague Dawley rats. Results: The selected hydrogel showed stability in culture media, had a gelation time of 2.8 minutes, showed a highly porous microstructure by scanning electron microscope, and was morphologically intact in vivo for 14 days after injection. Histological and immunohistochemical analyses and real-time PCR confirmed the chondrogenesis ability of hDPSCs embedded in NC-CS/GP-21 hydrogel. Conclusion: Our results suggest that nanocellulose-chitosan thermosensitive hydrogel is a biocompatible, injectable, mechanically stable and slowly degradable scaffold. hDPSCs embedded in NC-CS/GP-21 hydrogel is a promising, minimally invasive, stem cell-based strategy for cartilage regeneration.


Assuntos
Cartilagem/fisiologia , Diferenciação Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Polpa Dentária/citologia , Hidrogéis/farmacologia , Regeneração/efeitos dos fármacos , Células-Tronco/citologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cartilagem/citologia , Cartilagem/efeitos dos fármacos , Celulose/química , Quitosana/química , Humanos , Hidrogéis/química , Porosidade , Ratos , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos , Tecidos Suporte/química
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2675-2678, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018557

RESUMO

In the recent years, Bioresorbable Vascular Scaffolds (BVS) for the treatment of atherosclerosis have been introduced. InSilc is a cloud based in silico clinical trial (ISCT) platform for drug-eluting BVS. The platform integrates multidisciplinary and multiscale models predicting the BVS performance. In this study, we present a use case scenario and demonstrate the functioning of the individual modules and of the whole pipeline and the ability to predict BVS short, medium, long-term outcomes.


Assuntos
Implantes Absorvíveis , Stents Farmacológicos , Ensaios Clínicos como Assunto , Simulação por Computador , Tecidos Suporte , Resultado do Tratamento
7.
Int J Nanomedicine ; 15: 6945-6960, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061361

RESUMO

Background: Natural clay nanomaterials are an emerging class of biomaterial with great potential for tissue engineering and regenerative medicine applications, most notably for osteogenesis. Materials and Methods: Herein, for the first time, novel tissue engineering scaffolds were prepared by 3D bioprinter using nontoxic and bioactive natural attapulgite (ATP) nanorods as starting materials, with polyvinyl alcohol as binder, and then sintered to obtain final scaffolds. The microscopic morphology and structure of ATP particles and scaffolds were observed by transmission electron microscope and scanning electron microscope. In vitro biocompatibility and osteogenesis with osteogenic precursor cell (hBMSCs) were assayed using MTT method, Live/Dead cell staining, alizarin red staining and RT-PCR. In vivo bone regeneration was evaluated with micro-CT and histology analysis in rat cranium defect model. Results: We successfully printed a novel porous nano-ATP scaffold designed with inner channels with a dimension of 500 µm and wall structures with a thickness of 330 µm. The porosity of current 3D-printed scaffolds ranges from 75% to 82% and the longitudinal compressive strength was up to 4.32±0.52 MPa. We found firstly that nano-ATP scaffolds with excellent biocompatibility for hBMSCscould upregulate the expression of osteogenesis-related genes bmp2 and runx2 and calcium deposits in vitro. Interestingly, micro-CT and histology analysis revealed abundant newly formed bone was observed along the defect margin, even above and within the 3D bioprinted porous ATP scaffolds in a rat cranial defect model. Furthermore, histology analysis demonstrated that bone was formed directly following a process similar to membranous ossification without any intermediate cartilage formation and that many newly formed blood vessels are within the pores of 3D-printed scaffolds at four and eight weeks. Conclusion: These results suggest that the 3D-printed porous nano-ATP scaffolds are promising candidates for bone tissue engineering by osteogenesis and angiogenesis.


Assuntos
Regeneração Óssea/fisiologia , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Osso e Ossos/fisiologia , Cálcio/metabolismo , Chlorocebus aethiops , Condrogênese , Força Compressiva , Regulação da Expressão Gênica , Humanos , Compostos de Magnésio/química , Masculino , Teste de Materiais , Nanotubos/química , Osteogênese/fisiologia , Álcool de Polivinil/química , Porosidade , Impressão Tridimensional , Ratos Sprague-Dawley , Compostos de Silício/química , Células Vero , Microtomografia por Raio-X
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2262-2265, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018458

RESUMO

Cardiac muscle cells are the fundamental building blocks of the heart, yet little is known about their mechanical properties in either healthy or diseased states. While many have explored unloaded myocyte behavior under a variety of interventions, methods for force measurements are limited due to cell fragility. Here, we present a custom device for manipulation and mechanical testing of hydrogels embedded with delicate cardiac muscle cells. Consisting of a custom disposable flexure, which is easily interchangeable, the device has the potential for high throughput testing of cell-gel constructs. Additionally, the mechanical testing device is the size of a microscope slide - appropriate for use in most microscopes, for simultaneous imaging of the sample. The mechanical properties of a gelatin-methacryloyl hydrogel sample were assessed, and 3D volumes of gel imaged using a confocal microscope. The Young's modulus of the gel was found to be 33kPa.Clinical Relevance- High-throughput testing provides the potential to gain insight into cardiac cell mechanics. Experimentation under the influence of a variety of pharmacological interventions could improve the rate at which treatments for cardiac disease are developed. Furthermore, methods may be extended to other embedded biological tissues.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Gelatina , Fenômenos Mecânicos , Tecidos Suporte
9.
Cell Prolif ; 53(10): e12907, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32951298

RESUMO

OBJECTIVE: Tissue engineering is a promising strategy for repair of large bone defect. However, the immune system reactions to biological scaffold are increasingly being recognized as a crucial factor influencing regeneration efficacy. In this study, a bone-bioactive hydrogel bead loaded with interleukin-4 (IL-4) was used to regulate macrophages polarization and accelerate bone regeneration. METHODS: IL-4-loaded calcium-enriched gellan gum (Ca-GG + IL-4) hydrogel beads were synthesised. And the effect on cell behaviour was detected. Furthermore, the effect of the Ca-GG + IL-4 hydrogel bead on macrophage polarization and the effect of macrophage polarization on bone mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation were evaluated in vitro and in vivo. RESULTS: BMSCs were able to survive in the hydrogel regardless of whether IL-4 was incorporated. Immunofluorescence staining and qPCR results revealed that Ca-GG + IL-4 hydrogel bead could promote M2 macrophage polarization and increase transforming growth factor (TGF)-ß1 expression level, which activates the TGF-ß1/Smad signalling pathway in BMSCs and promotes osteogenic differentiation. Moreover, immunohistochemical analysis demonstrated Ca-GG + IL-4 hydrogel bead could promote M2 macrophage polarization and reduce cell apoptosis in vivo. In addition, micro-CT and immunohistochemical analysis at 12 weeks post-surgery showed that Ca-GG + IL-4 hydrogel bead could achieve superior bone defect repair efficacy in vivo. CONCLUSIONS: The Ca-GG + IL-4 hydrogel bead effectively promoted bone defect regeneration via regulating macrophage polarization, reducing cell apoptosis and promoting BMSCs osteogenesis through TGF-ß1/Smad pathway. Therefore, it is a promising strategy for repair of bone defect.


Assuntos
Regeneração Óssea , Diferenciação Celular/efeitos dos fármacos , Hidrogéis/química , Interleucina-4/farmacologia , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tecidos Suporte/química , Animais , Apoptose/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Interleucina-4/química , Interleucina-4/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Polissacarídeos Bacterianos/química , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Proteínas Smad/metabolismo , Engenharia Tecidual , Fator de Crescimento Transformador beta1/metabolismo
10.
Int J Nanomedicine ; 15: 6097-6111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884266

RESUMO

The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discuss the role of polymer scaffolds and various growth factors involved in cartilage tissue engineering. Several growth factor delivery strategies based on the polymer scaffolds will also be discussed, with examples from recent studies highlighting the importance of spatiotemporal strategies for the controlled delivery of single or multiple growth factors in cartilage tissue engineering applications.


Assuntos
Cartilagem , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Polímeros/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Cartilagem/citologia , Cartilagem/fisiologia , Condrogênese , Matriz Extracelular/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Células-Tronco
11.
Nature ; 585(7826): 574-578, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32939089

RESUMO

Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1-4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host-microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.


Assuntos
Homeostase , Intestinos/embriologia , Morfogênese , Organoides/embriologia , Tecidos Suporte , Animais , Padronização Corporal , Diferenciação Celular , Linhagem da Célula , Cryptosporidium parvum/patogenicidade , Células-Tronco Embrionárias Humanas/citologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Intestinos/citologia , Intestinos/parasitologia , Intestinos/patologia , Camundongos , Modelos Biológicos , Organoides/citologia , Organoides/parasitologia , Organoides/patologia , Regeneração , Medicina Regenerativa , Células-Tronco , Técnicas de Cultura de Tecidos/métodos , Engenharia Tecidual
12.
Int J Nanomedicine ; 15: 6761-6777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982232

RESUMO

Purpose: Guided bone regeneration (GBR) therapy, which is a widely used technique in clinical practice and is effective in improving the repair of alveolar bone defects or bone mass deficiency regeneration, requires the use of membrane materials with good biocompatibility, barrier function, rigidity matching the space maintenance ability, economic benefits and excellent clinical applicability. The aim of this study was to develop an electrospun attapulgite (ATT)-doped poly (lactic-co-glycolic acid) (PLGA) scaffold (PLGA/ATT scaffold) as a novel material for GBR applications. Methods and Results: Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to determine the morphology and the crystalline structure of the PLGA/ATT scaffolds, respectively. Porosity and contact-angle measurements were also carried out to further characterize the physical properties of the PLGA/ATT scaffolds. The results of in vitro studies showed that bone marrow mesenchymal stem cells (BMSCs) attached more readily to and spread better over the PLGA/ATT scaffolds than the Bio-Gide membrane. Furthermore, in the in vitro osteoinductive experiments with BMSCs, the PLGA/ATT scaffolds were found to enhance the activity of alkaline phosphatase (ALP), promote the formation of mineralized bone nodules, and up-regulate the expression of several osteogenic markers-namely, runt-related transcription factor 2, alkaline phosphatase, osteopontin, and osteocalcin-which are similar to the effects of the Bio-Gide membrane. Further, in in vivo studies, the results of sequential fluorescent labeling, micro-computed tomography, and histological analysis suggest that using the PLGA/ATT scaffolds for repairing V-shaped buccal dehiscence on a dog's tooth root improved bone regeneration, which is not only similar to the result obtained using the Bio-Gide membrane but also much better than that obtained using PLGA scaffolds and the negative control. Conclusion: To achieve satisfactory therapeutic results and to lower the cost of GBR treatment, this study provided a promising alternative material of bio-degradable membrane in clinical treatment.


Assuntos
Perda do Osso Alveolar/terapia , Regeneração Óssea/fisiologia , Compostos de Magnésio/farmacologia , Compostos de Silício/farmacologia , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Calcificação Fisiológica , Colágeno , Cães , Expressão Gênica , Gengiva/citologia , Humanos , Compostos de Magnésio/química , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteogênese/fisiologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Ratos Sprague-Dawley , Compostos de Silício/química , Raiz Dentária/diagnóstico por imagem , Microtomografia por Raio-X
13.
PLoS One ; 15(9): e0239152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956427

RESUMO

Volumetric muscle loss (VML) is the loss of skeletal muscle that results in significant and persistent impairment of function. The unique characteristics of craniofacial muscle compared trunk and limb skeletal muscle, including differences in gene expression, satellite cell phenotype, and regenerative capacity, suggest that VML injuries may affect craniofacial muscle more severely. However, despite these notable differences, there are currently no animal models of craniofacial VML. In a previous sheep hindlimb VML study, we showed that our lab's tissue engineered skeletal muscle units (SMUs) were able to restore muscle force production to a level that was statistically indistinguishable from the uninjured contralateral muscle. Thus, the goals of this study were to: 1) develop a model of craniofacial VML in a large animal model and 2) to evaluate the efficacy of our SMUs in repairing a 30% VML in the ovine zygomaticus major muscle. Overall, there was no significant difference in functional recovery between the SMU-treated group and the unrepaired control. Despite the use of the same injury and repair model used in our previous study, results showed differences in pathophysiology between craniofacial and hindlimb VML. Specifically, the craniofacial model was affected by concomitant denervation and ischemia injuries that were not exhibited in the hindlimb model. While clinically realistic, the additional ischemia and denervation likely created an injury that was too severe for our SMUs to repair. This study highlights the importance of balancing the use of a clinically realistic model while also maintaining control over variables related to the severity of the injury. These variables include the volume of muscle removed, the location of the VML injury, and the geometry of the injury, as these affect both the muscle's ability to self-regenerate as well as the probability of success of the treatment.


Assuntos
Traumatismos Faciais/cirurgia , Músculos Faciais/cirurgia , Regeneração Tecidual Guiada/métodos , Doenças Musculares/cirurgia , Engenharia Tecidual/métodos , Animais , Modelos Animais de Doenças , Face/cirurgia , Traumatismos Faciais/complicações , Músculos Faciais/fisiopatologia , Feminino , Humanos , Masculino , Doenças Musculares/etiologia , Recuperação de Função Fisiológica , Regeneração/fisiologia , Ovinos , Tecidos Suporte
14.
Adv Exp Med Biol ; 1298: 79-103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32902726

RESUMO

Conventional treatment approaches in irreversible pulpitis and apical periodontitis include the disinfection of the pulp space followed by filling with various materials, which is commonly known as the root canal treatment. Disadvantages including the loss of tooth vitality and defense mechanism against carious lesions, susceptibility to fractures, discoloration and microleakage led to the development of regenerative therapies for the dentin pulp-complex. The goal of dentin-pulp tissue regeneration is to reestablish the physiological pulp function such as pulp sensibility, pulp repair capability by mineralization and pulp immunity. Recent dentin-pulp tissue regeneration approaches can be divided into cell homing and cell transplantation. Cell based approaches include a suitable scaffold for the delivery of potent stem cells with or without bioactive molecules into the root canal system while cell homing is based on the recruitment of host endogenous stem cells from the resident tissue including periapical region or dental pulp. This review discusses the recent treatment modalities in dentin-pulp tissue regeneration through tissue engineering and current challenges and trends in this field of research.


Assuntos
Engenharia Tecidual , Polpa Dentária , Dentina , Odontologia , Células-Tronco , Tecidos Suporte , Cicatrização
15.
PLoS One ; 15(9): e0238471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870933

RESUMO

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold.


Assuntos
Transplante Ósseo/métodos , Osso e Ossos/patologia , Tecidos Suporte/química , Substitutos Ósseos/farmacologia , Força Compressiva , Análise de Elementos Finitos , Hidrodinâmica , Teste de Materiais , Permeabilidade , Porosidade , Pressão , Estresse Mecânico , Engenharia Tecidual/métodos
16.
Int J Nanomedicine ; 15: 6373-6383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904686

RESUMO

Background: The treatment of tendon injuries remains a challenging problem in clinical due to their slow and insufficient natural healing process. Scaffold-based tissue engineering provides a promising strategy to facilitate tendon healing and regeneration. However, many tissue engineering scaffolds have failed due to their poor and unstable mechanical properties. To address this, we fabricated nanofibrous polycaprolactone/methacrylated poly(trimethylene carbonate) (PCL/PTMC-MA) composite scaffolds via electrospinning. Materials and Methods: PTMC-MA was characterized by nuclear magnetic resonance. Fiber morphology of composite scaffolds was evaluated using scanning electron microscopy. The monotonic tensile test was performed for determining the mechanical properties of composite scaffolds. Cell viability and collagen deposition were assessed via PrestoBlue assay and enzyme-linked immunosorbent assay, respectively. Results: These PCL/PTMC-MA composite scaffolds had an increase in mechanical properties as PTMC-MA content increase. After photo-crosslinking, they showed further enhanced mechanical properties including creep resistance, which was superior to pure PCL scaffolds. It is worth noting that photo-crosslinked PCL/PTMC-MA (1:3) composite scaffolds had a Young's modulus of 31.13 ± 1.30 MPa and Max stress at break of 23.80 ± 3.44 MPa that were comparable with the mechanical properties of native tendon (Young's modulus 20-1200 MPa, max stress at break 5-100 MPa). In addition, biological experiments demonstrated that PCL/PTMC-MA composite scaffolds were biocompatible for cell adhesion, proliferation, and differentiation.


Assuntos
Células-Tronco Mesenquimais/citologia , Nanofibras/química , Fotoquímica/métodos , Tecidos Suporte/química , Animais , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Dioxanos/química , Teste de Materiais , Camundongos Endogâmicos C57BL , Poliésteres/química , Polímeros/química , Regeneração , Tendões/fisiologia
17.
Nat Commun ; 11(1): 4504, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908131

RESUMO

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.


Assuntos
Microambiente Celular/imunologia , Sistemas de Liberação de Medicamentos/instrumentação , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Tecidos Suporte , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/administração & dosagem , Lipossomos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Neural/farmacocinética , Regeneração Nervosa/imunologia , Ratos , Recuperação de Função Fisiológica/imunologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia
18.
J Endod ; 46(9S): S128-S134, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950184

RESUMO

Stem cell-mediated regenerative endodontics has reached the human clinical trial phase; however, many issues still exist that prevent such technology to be a widely used clinical practice. These issues are not straightforward and are complicated. They should be because pulp regeneration is dealing with a small dead-end space. In addition, when regeneration is needed, the space is often heavily infected. The true standard of pulp regeneration should be everything except generation of some fibrous connective tissue and amorphous mineral deposit. As of now, we are still far short of reaching the standard of complete vascularized and innervated pulp regeneration with newly formed tubular dentin in all types of teeth. Thus, we need to go back to the bench and use established animal models or create new animal models to tackle those issues. This article will address several key issues including the possibility of pulp regeneration in small canals of molar teeth by enhancing the neovascularization, and whether the organized tubular dentin can be generated on the canal walls. Data from our semi-orthotopic tooth fragment mouse model have shown that complete pulp regeneration using dental pulp stem cells (DPSCs) in small canal has been inconsistent because of limited blood supply. This inconsistency is similar in our orthotopic miniature swine model, although in some cases vascularized pulp-like tissue can be formed throughout the canal space after DPSC transplantation. Furthermore, no tubular dentin was observed in the orthotopic pulp regeneration, despite the fact that DPSCs have the capacity to generate some tubular dentin-like structure in the hydroxyapatite/tricalcium phosphate-mediated ectopic pulp/dentin formation model in mice. Potential strategies to be tested to address these regeneration issues are discussed herein.


Assuntos
Dentina , Regeneração , Animais , Diferenciação Celular , Polpa Dentária , Humanos , Camundongos , Células-Tronco , Suínos , Engenharia Tecidual , Tecidos Suporte
19.
J Endod ; 46(9S): S143-S149, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950186

RESUMO

In past years, both cell transplantation and cell homing have been explored for dental pulp tissue engineering. Sufficient evidence shows that after cell transplantation, the regeneration of a functional dentin-pulp complex is possible. A new milestone was reached recently. The concept has now been evaluated in clinical studies. However, the approach is afflicted with high efforts and operating expenses; thus cell homing might be a viable alternative. In this article, the latest developments on the recruitment of resident stem cells by dentin-derived growth factors in injectable fibrin-based scaffold materials will be discussed.


Assuntos
Polpa Dentária , Engenharia Tecidual , Dentina , Regeneração , Células-Tronco , Tecidos Suporte
20.
J Endod ; 46(9S): S81-S89, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950199

RESUMO

Regenerative dentistry has come a long way from pulp capping to pulp regeneration research, which aims to regenerate the pulp-dentin complex and restore its functions compromised by pulp injury and/or inflammation. Because of unique anatomic limitations of the tooth structure, engineering a suitable microenvironment that facilitates angio/vasculogenesis and innervation is a challenging task. Cell-based tissue engineering approaches have shown great potential in achieving this goal. Biomedical approaches in creating a regenerative microenvironment are mainly represented by either scaffold-based or scaffold-free strategies. The scaffold-based strategy mainly relies on the use of biomaterials to create a structural base that supports cells throughout the process of tissue formation. The scaffold could be a classic 3-dimensional construct with interconnected pores, a hydrogel with cells embedded in it, or a combination of these 2. The scaffold-free approach has been considered a bottom-up strategy that uses cell sheets, spheroids, or tissue strands as building blocks. The outcome of this strategy relies on the capacity of these building blocks to secrete a favorable extracellular matrix and to fuse into larger tissue constructs. Both the scaffold-free and scaffold-based systems are required as complementary, rather than competing, approaches for pulp regeneration. A combined synergetic strategy, through which multicellular building blocks could be integrated with robust 3-dimensional scaffolds, might represent an optimal solution to circumvent some of the major drawbacks of the current methods in pulp regeneration while concurrently fostering their advantages.


Assuntos
Polpa Dentária , Tecidos Suporte , Diferenciação Celular , Regeneração , Engenharia Tecidual
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