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1.
Front Oncol ; 14: 1366079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939341

RESUMO

Objective: To investigate the feasibility of leg wound closure and reconstruction of maxillofacial soft defect by a fusiform-designed skin paddle in fibula free flap (FFF). Methods: Fifty patients who underwent FFF for reconstruction of maxillofacial soft defect were divided into two groups. The fusiform group (20 patients) was treated using a fusiform-designed skin paddle in FFF (skin paddle width less than 2 cm), and leg wound was closed using primary suturing. Reconstruction of the maxillofacial soft defect or filling of dead space was achieved by folding the fusiform skin paddle. The conventional group (30 patients) was treated using the conventional-designed skin paddle (skin paddle width no less than 2.5 cm). The leg wound was closed using mattress suturing or skin graft, while reconstruction of the maxillofacial soft defect or filling of dead space by conventional way. The average postoperative length of hospital stay, healing time of leg wound, and post-surgical complications were recorded at least 6 months after the surgery. Results: Compared with traditional method, the fusiform-designed skin paddle reduced the average healing time of the leg wound (fusiform group: 11.05 days, conventional group: 14.77 days, P < 0.05). The average length-to-width ratio in fusiform group was significantly greater than that of in conventional group (fusiform group: 5.85, conventional group: 2.93, P < 0.05), and no difference was observed on the graft size of skin paddle between two groups (fusiform group: 23.13, conventional group: 27.13, P > 0.05). The post-surgical early complications of the leg wound in the conventional group were higher than that of in the fusiform group (fusiform group: 0%, conventional group: 6.67%), while the post-surgical late complication of the donor site between the two groups showed no case. Healing disorders of maxillofacial soft reconstruction in the conventional group were higher than that of in the fusiform group (fusiform group: 5.26%, conventional group: 20.69%). Conclusions: Fusiform-designed skin paddle for closure of the leg wound and maxillofacial soft defect is a feasible alternative to the conventional- designed skin paddle. The fusiform- designed skin paddle resulted in the less postoperative length of hospital stay, shorter healing time of leg wound and less complication.

2.
Adv Healthc Mater ; : e2400624, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782037

RESUMO

Electrical stimulation (ES) has a remarkable capacity to regulate neuronal differentiation and neurogenesis in the treatment of various neurological diseases. However, wired devices connected to the stimulating electrode and the mechanical mismatch between conventional rigid electrodes and soft tissues restrict their motion and cause possible infections, thereby limiting their clinical utility. An approach integrating the advantages of wireless techniques and soft hydrogels provides new insights into ES-induced nerve regeneration. Herein, a flexible and implantable wireless ES-responsive electrode based on an annular gelatin methacrylate-polyaniline (Gel/Pani) hydrogel is fabricated and used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The Gel/Pani hydrogels exhibit favorable biocompatibility, biodegradability, conductivity, and compression resistance. The annular electrode of the Gel/Pani conductive hydrogel (AECH) supports neural stem cell growth, while the applied wireless ES facilitates neuronal differentiation and the formation of functional neural networks in vitro. Furthermore, AECH is implanted in vivo in rats with ischemic stroke and the results reveal that AECH-mediated wireless ES significantly ameliorates brain impairment and neurological function by activating endogenous neurogenesis. This novel flexible hydrogel system addresses wireless stimulation and implantable technical challenges, holding great potential for the treatment of neurodegenerative diseases.

3.
J Mater Chem B ; 12(9): 2354-2363, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38344940

RESUMO

Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin-hyaluronic acid (Gel-HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel-HA hydrogel surrounding the GF. The "soft" Gel-HA hydrogel and "stiff" GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel-HA/GF scaffold proliferated well and retained the CD34+CD38- immunophenotype and pluripotency, suggesting that the Gel-HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.


Assuntos
Medula Óssea , Grafite , Grafite/farmacologia , Hidrogéis/química , Células-Tronco Hematopoéticas , Células da Medula Óssea
4.
Cells Tissues Organs ; 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812928

RESUMO

BACKGROUND: An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a common property of Alzheimer's disease and the degeneration of functional BFCNs is related to learning and memory deficits. As a biocompatible and conductive scaffold for growth of neural stem cells, three-dimensional graphene foam (3D-GF) supports applications in tissue engineering and regenerative medicine. Although its effects on differentiation have been demonstrated, the effect of 3D-GF scaffold on the generation of BFCNs still remains unknown. METHODS: In this study, we used 3D-GF as a culture substrate for neural progenitor cells (NPCs) and demonstrated that this scaffold material promotes the differentiation of BFCNs while maintaining excellent cell viability and proliferation. RESULTS: Immunofluorescence analysis, RT-PCR, western blotting and ELISA revealed that the proportion of BFCNs at 21 days of differentiation reached approximately 30.5% on 3D-GF compared with TCPS group that only presented 9.7%. Furthermore, a cell adhesion study suggested that 3D-GF scaffold enhances the expression of adhesion proteins including vinculin, integrin and N-cadherin. These findings indicate that 3D-GF scaffold materials are preferable candidates for the differentiation of BFCNs from NPCs. CONCLUSIONS: These results suggest new opportunities for the application of 3D-GF scaffold as a neural scaffold for cholinergic neurons therapies based on NPCs.

5.
Biomater Sci ; 11(19): 6537-6544, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37593879

RESUMO

The extracellular matrix (ECM) is a natural microenvironment pivotal for stem cell survival, as well as proliferation, differentiation and metastasis, composed of a variety of biological molecular complexes secreted by resident cells in tissues and organs. Heparan sulfate proteoglycan (HSPG) is a type of ECM protein that contains one or more covalently attached heparan sulfate chains. Heparan sulphate chains have high affinity with growth factors, chemokines and morphogens, acting as cytokine-binding domains of great importance in development and normal physiology. Herein, we constructed endogenous HSPG2 overexpression in mouse embryonic fibroblasts based on the CRISPR/Cas9 synergistic activation mediator system and then fabricated a cell-derived HSPG2 functional ECM (ECMHSPG2). The ECMHSPG2 is capable of enriching basic fibroblast growth factor (bFGF), which binds more strongly than the negative control ECM. With a growing bFGF concentration, ECMHSPG2 could better maintain neural stem cell (NSCs) stemness and promote NSC proliferation and differentiation in culture. These findings provide a precise design strategy for producing a specific cell-derived ECM for biomaterials in research and regenerative medicine.


Assuntos
Sistemas CRISPR-Cas , Células-Tronco Neurais , Animais , Camundongos , Sistemas CRISPR-Cas/genética , Fibroblastos/metabolismo , Matriz Extracelular/metabolismo , Proteoglicanas de Heparan Sulfato , Heparitina Sulfato/metabolismo , Células-Tronco Neurais/metabolismo
6.
ACS Appl Mater Interfaces ; 15(17): 20625-20637, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37078820

RESUMO

The limited self-repair capacity of articular cartilage has motivated the development of stem cell therapy based on artificial scaffolds that mimic the extracellular matrix (ECM) of cartilage tissue. In view of the specificity of articular cartilage, desirable tissue adhesiveness and stable mechanical properties under cyclic mechanical loads are critical for cartilage scaffolds. Herein, we developed an injectable and degradable organic-inorganic hybrid hydrogel as a cartilage scaffold based on polyhedral oligomeric silsesquioxane (POSS)-cored polyphosphate and polysaccharide. Specifically, acrylated 8-arm star-shaped POSS-poly(ethyl ethylene phosphate) (POSS-8PEEP-AC) was synthesized and cross-linked with thiolated hyaluronic acid (HA-SH) to form a degradable POSS-PEEP/HA hydrogel. Incorporation of POSS in the hydrogel increased the mechanical properties. The POSS-PEEP/HA hydrogel showed enzymatic biodegradability and favorable biocompatibility, supporting the growth and differentiation of human mesenchymal stem cells (hMSCs). The chondrogenic differentiation of encapsulated hMSCs was promoted by loading transforming growth factor-ß3 (TGF-ß3) in the hydrogel. In addition, the injectable POSS-PEEP/HA hydrogel was capable of adhering to rat cartilage tissue and resisting cyclic compression. Furthermore, in vivo results revealed that the transplanted hMSCs encapsulated in the POSS-PEEP/HA hydrogel scaffold significantly improved cartilage regeneration in rats, while the conjugation of TGF-ß3 achieved a better therapeutic effect. The present work demonstrated the potential of the injectable, biodegradable, and mechanically enhanced POSS-PEEP/HA hybrid hydrogel as a scaffold biomaterial for cartilage regeneration.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Polifosfatos , Cartilagem Articular/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Condrogênese , Regeneração , Polissacarídeos/farmacologia , Alicerces Teciduais , Engenharia Tecidual
7.
Adv Healthc Mater ; 12(20): e2203132, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37001492

RESUMO

Many neurons undergo apoptosis after ischemic stroke. In the brain, neurogenesis has the potential for neuronal replacement and can be activated by external conditions to repair the injury. Crocetin (CRO), naturally extracted from the plant saffron, acts as a neuroprotective agent for ischemic stroke. However, the underlying mechanism remains unknown. In this work, the effect of CRO on neural stem cell (NSC) behaviors and subventricular zone neurogenesis is investigated. Initially, NSCs are incubated with different concentrations of CRO to detect the cell proliferation and differentiation in vitro. Second, ischemic stroke induced rats are treated with CRO using nimodipine (NMDP) as a comparison. The behavioral functions, infarcted volume, and apoptotic Nissl bodies of rats are noticeably improved after CRO-treatment, comparable to those of NMDP. In addition, the increased regional cerebral blood flow and promoted neuronal differentiation are achieved by CRO-treatment. Brain tissue examination shows significantly increased neuronal regeneration in the focal ischemic injury area. Meanwhile, the length of neurites is prolonged, indicating that CRO could potentially promote neurite extension to enhance cell-cell communication. These findings demonstrate that CRO facilitated the neuronal differentiation of NSCs by activating subventricular zone neurogenesis in damaged cortex and striatum sites to repair ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Células-Tronco Neurais , Acidente Vascular Cerebral , Ratos , Animais , Neurônios/fisiologia , Neurogênese/fisiologia , Acidente Vascular Cerebral/terapia
8.
J Mater Chem B ; 10(47): 9755-9769, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36444902

RESUMO

Hematopoietic stem cell (HSC) transplantation provides an effective platform for the treatment of hematological disorders. However, the donor shortage of HSCs and immune responses severely restrict the clinical applications of HSCs. Compared to allogeneic transplantation, autogenous transplantation poses less risk to the immune system, but the problem associated with insufficient HSCs remains a substantial challenge. A significant strategy for obtaining sufficient HSCs is to promote the expansion of HSCs. In vivo, a bone marrow microenvironment supports the survival and hematopoiesis of HSCs. Therefore, it is crucial to establish a platform that mimics the features of a bone marrow microenvironment for the in vitro expansion of HSCs. Three-dimensional (3D) scaffolds have emerged as the most powerful tools to mimic cellular microenvironments for the growth and proliferation of stem cells. Biomedical polymers have been widely utilized as cell scaffolds due to their advantageous features including favorable biocompatibility, biodegradability, as well as adjustable physical and chemical properties. This review focuses on recent advances in the study of biomedical polymer scaffolds that mimic bone marrow microenvironments for the in vitro expansion of HSCs. Bone marrow transplantation and microenvironments are first introduced. Then, biomedical polymer scaffolds for the expansion of HSCs and future prospects are summarized and discussed.


Assuntos
Medula Óssea , Polímeros , Células-Tronco Hematopoéticas
9.
Biomater Sci ; 10(19): 5707-5718, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36039673

RESUMO

The regeneration of myelin sheaths is the ultimate goal of the treatment of demyelination disease, including multiple sclerosis (MS). However, current drugs for MS mainly target the immune system and can only slow down the disease development and do not promote the differentiation of oligodendrocyte precursor cells (OPCs) abundant in the myelin injury region into mature oligodendrocytes to form a new myelin sheath. Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of OPC proliferation and differentiation into mature oligodendrocytes. Exosomes, a kind of nanoscale membrane vesicle secreted by cells, can be used as potential therapeutic drug delivery vectors for central nervous system diseases. Here, brain-targeted modification and BDNF intracellular-loaded exosomes were produced through engineering HEK293T cells, which can promote the differentiation of OPCs into mature oligodendrocytes in vitro. The intranasal administration of the brain-targeted engineered exosome-mediated BDNF was a highly effective delivery route to the brain and had a significant therapeutic effect on remyelination and motor coordination ability improvement in demyelination model mice. The combination of intranasal administration with brain-targeted and BDNF-loaded designed exosomes provides a strategy for efficient drug delivery and treatment of central nervous system diseases.


Assuntos
Exossomos , Esclerose Múltipla , Remielinização , Administração Intranasal , Animais , Encéfalo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Diferenciação Celular , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Oligodendroglia , Remielinização/fisiologia
10.
J Extracell Vesicles ; 11(8): e12255, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35932288

RESUMO

Glioma is one of the primary malignant brain tumours in adults, with a poor prognosis. Pharmacological reagents targeting glioma are limited to achieve the desired therapeutic effect due to the presence of blood-brain barrier (BBB). Effectively crossing the BBB and specifically targeting to the brain tumour are the major challenge for the glioma treatments. Here, we demonstrate that the well-defined small extracellular vesicles (sEVs) with dual-targeting drug delivery and cell-penetrating functions, modified by Angiopep-2 and trans-activator of transcription peptides, enable efficient and specific chemotherapy for glioma. The high efficiency of engineered sEVs in targeting BBB and glioma was assessed in both monolayer culture cells and BBB model in vitro, respectively. The observed high targeting efficiency was re-validated in subcutaneous tumour and orthotopic glioma mice models. After loading the doxorubicin into dual-modified functional sEVs, this specific dual-targeting delivery system could cross the BBB, reach the glioma, and penetrate the tumour. Such a mode of drug delivery significantly improved more than 2-fold survival time of glioma mice with very few side effects. In conclusion, utilization of the dual-modified sEVs represents a unique and efficient strategy for drug delivery, holding great promise for the treatments of central nervous system diseases.


Assuntos
Vesículas Extracelulares , Glioma , Animais , Linhagem Celular Tumoral , Vesículas Extracelulares/patologia , Glioma/tratamento farmacológico , Camundongos , Peptídeos/uso terapêutico
11.
Biomed Mater ; 17(1)2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34874314

RESUMO

Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Células-Tronco Neurais , Colágeno/metabolismo , Exossomos/metabolismo , Matriz Extracelular/metabolismo , Neurogênese
12.
Adv Healthc Mater ; 10(11): e2100027, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33887103

RESUMO

Electrical stimulation (ES) offers significant advantages in modulating the behavior of stem cells on conductive scaffolds for neural tissue engineering. However, it is necessary to realize wireless ES to avoid the use of external wires in tissues. Thus, herein, a strategy is reported to develop a stem cell scaffold that allows wireless ES. A conductive annular graphene substrate is designed and grown by chemical vapor deposition; this substrate is used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The substrate shows excellent biocompatibility for the culture of neural stem cells (NSCs). The results indicate that the applied wireless ES enhances neuronal differentiation, facilitates the formation of neurites, and does not substantially affect the viability and stemness maintenance of NSCs. Collectively, this system provides a strategy for achieving synergy between wireless ES and conductive scaffolds for neural regenerative medicine, which can be further utilized for the regeneration of other tissues.


Assuntos
Células-Tronco Neurais , Alicerces Teciduais , Diferenciação Celular , Estimulação Elétrica , Engenharia Tecidual
13.
Nano Lett ; 20(10): 7043-7051, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32915578

RESUMO

The control of cell-microenvironment interactions plays a pivotal role in constructing specific scaffolds for tissue engineering. Here, we fabricated a 3D free-standing ordered graphene (3D-OG) network with a precisely defined pattern. When primary cortical cells are cultured on 3D-OG scaffolds, they form well-defined 3D connections. Astrocytes have a more ramified shape similar to that seen in vivo because of the nanosized ripples and wrinkles on the surface of graphene skeleton. Neurons have axons and dendrites aligned along the graphene skeleton, allowing the formation of neuronal networks with highly controlled connections. Neuronal networks have higher electrical activity with functional signaling over a long distance along the graphene skeleton. Our study, for the first time, investigated the geometrical cues on ordered neuronal growth and network formation with the support of graphene in 3D, which therefore advanced the development of customized scaffolds for brain-machine interfaces or neuroprosthetic devices.


Assuntos
Grafite , Axônios , Neurogênese , Neurônios , Engenharia Tecidual , Alicerces Teciduais
14.
Small ; 16(3): e1906273, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31840420

RESUMO

Reducing amyloid-ß (Aß) accumulation could be a potential therapeutic approach for Alzheimer's disease (AD). Particular functional biomolecules in exosomes vested by the microenvironment in which the original cells resided can be transferred to recipient cells to improve pathological conditions. However, there are few reports addressing whether exosomes derived from cells cultured on scaffolds with varying dimension can reduce Aß deposition or ameliorate cognitive decline for AD therapy. Herein, both 3D graphene scaffold and 2D graphene film are used as the matrix for human umbilical cord mesenchymal stem cell culture, from which the supernatants are obtained to isolate exosomes. The levels of 195 kinds of miRNAs and proteins, including neprilysin, insulin-degrading enzyme and heat shock protein 70, in 3D-cultured exosomes (3D-Exo) are dramatically different from those obtained from 2D culture. Hence, 3D-Exo could up-regulate the expression of α-secretase and down-regulate the ß-secretase to reduce Aß production in both AD pathology cells and transgenic mice, through their special cargo. With rescuing Aß pathology, 3D-Exo exerts enhanced therapeutic effects on ameliorating the memory and cognitive deficits in AD mice. These findings provide a novel clinical application for scaffold materials and functional exosomes derived from stem cells.


Assuntos
Doença de Alzheimer/terapia , Exossomos/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Transgênicos
15.
Carbohydr Polym ; 225: 115257, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521312

RESUMO

Extracellular matrix degradability meditates cell behaviors and gains increasing importance in the development of implantation materials for tissue engineering. Here, we developed a fully biodegradable hydrogel combining the unique features of synthetic polyphosphate polymer and natural polysaccharide polymer. Polyphosphate copolymer poly(butynyl phospholane)-random-poly(ethylethylene phosphate) (PBYP-r-PEEP) bearing pendent alkynes was synthesized through a facile one-pot reaction. Subsequently, thiol-yne "click" reaction was employed to fabricate the fully degradable and photocrosslinked hydrogel by mixing PBYP-r-PEEP with thiolated biodegradable hyaluronic acid (HA-SH). The generated HA/PPE hydrogels show viscoelastic properties and enzymatic biodegradability, supporting the growth of human mesenchymal stem cells (hMSCs). HA/PPE hydrogel is permissive to the covalent conjugation of cell-adhesive peptide RGD, which can enhance the cell-cell interactions. This HA/PPE hydrogel system provides a fully biodegradable platform that can support hMSCs growth and facilitate the formation of cell clustering, expanding the range of fully degradable materials for tissue engineering and regenerative medicine.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Polifosfatos/química , Polissacarídeos/química , Engenharia Tecidual , Implantes Absorvíveis , Adesão Celular , Comunicação Celular , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Substâncias Viscoelásticas/química
16.
Acta Biomater ; 88: 346-356, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30822551

RESUMO

Transplantation of neural progenitor cells (NPCs) can repair the damaged neurons and therefore holds significant promise as a new treatment strategy for Alzheimer's disease (AD). Development of functional scaffolds for the growth, proliferation, and differentiation of NPCs offers a useful approach for AD therapy. In our study, the functional scaffolds were obtained by fabrication of a poly(lactic-co-glycolic acid) (PLGA) nanofibrous mat by the electrospinning technique, followed by coating of a layer of graphene oxide (GO) and then physisorption of methylene blue (MB) under mild conditions. The precoating of GO on the nanofibrous scaffolds allows efficient loading and release of MB from the substrate for regulating the functions of NPCs. The NPCs cultured on the scaffolds remained in the quiescence phase due to the activation of autophagy signaling pathway by MB. Moreover, the MB-loaded nanofibrous scaffolds diminish tau phosphorylation and protect NPCs from apoptosis. Definitely, more work, especially the in vivo experiment, is highly desired to demonstrate the feasibility of the current strategy for AD treatment. STATEMENT OF SIGNIFICANCE: Transplantation of neural progenitor cells (NPCs) can repair the damaged neurons and hold significant promise as a new treatment strategy for Alzheimer's disease (AD). Development of functional scaffolds for the growth, proliferation, and differentiation of NPCs offers a novel and useful approach for AD therapy. In this work, we have developed a GO and MB sequentially coated PLGA nanofibrous mat as a new scaffold for NPC transplantation and tauopathy inhibition. The coating of GO that we have demonstrated significantly enhanced the loading and release of MB on the scaffolds. Furthermore, NPCs cultured on the nanofibrous scaffolds entered quiescence phase through the activation of autophagy signaling pathway, leading to improved performance of NPCs to cope with stressors of disease. More importantly, the release of MB from the scaffolds leads to attenuation of tauopathy and protection of NPCs, which may represent a novel, versatile, and effective therapeutic approach for AD and other neurodegenerative diseases.


Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Grafite/farmacologia , Azul de Metileno/farmacologia , Nanofibras/química , Células-Tronco Neurais/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Camundongos Endogâmicos C57BL , Nanofibras/ultraestrutura , Nestina/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas tau/metabolismo
17.
RSC Adv ; 9(22): 12667-12674, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35515836

RESUMO

A new class of stimuli responsive drug delivery systems is emerging to establish new paradigms for enhancing therapeutic efficacy. To date, most electro-responsive systems rely on noble metal electrodes that likely cause the limitations for implantation applications. Herein, a graphene/polypyrrole composite electrode (GN-PPy-FL) was fabricated based on two-dimensional (2D) graphene (GN) film and conductive and biocompatible polypyrrole (PPy) nanoparticles loaded with a negative drug model of fluorescein sodium (FL) via chemical oxidation polymerization. The conductive composite electrode was utilized as a drug carrier to realize the electrically controlled release of the FL. The release rate from conductive nanoparticles can be controlled by the applied voltages. The study provides a multi-stimuli responsive drug release system, demonstrating the potential applications of the controlled release of various drugs, peptides or proteins.

18.
ACS Biomater Sci Eng ; 5(10): 5295-5304, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33455234

RESUMO

Three-dimensional (3D) carbon-based scaffolds have rapidly risen in tissue engineering due to the excellent conductivity and unique topological structures. For specific in vivo application, it is desirable to maintain the rigidity and improve the toughness of scaffolds in response to the compression force from surrounding tissues. In light of the combined advantages of graphene and hydrogels, we here construct a 3D composite scaffold consisting of a graphene foam (GF) and a laminarin hydrogel (LAgel). The composite scaffold was fabricated by immersing the GF in an LA hydrogel precursor followed by exposure to ultraviolet (UV) radiation to form a photocross-linked LAgel surrounding the GF. This composite scaffold exhibited the improved toughness compared with the GF or LAgel. The 3D GF can support cell attachment and cell spreading of human mesenchymal stem cells (hMSCs), while the in situ-formed LAgel with cell adhesive peptide arginine-glycine-aspartic acid (RGD) conjugated can induce the cell migration. The results suggest that the approach to incorporate the LAgel with the 3D GF not only enhances the toughness of the scaffold but also offers a carrier to realize the cargo of biosignals to regulate cell behaviors, showing the potential of this composite scaffold for tissue regeneration.

19.
Adv Mater ; 30(52): e1806132, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30387225

RESUMO

Currently available 3D assemblies based on carbon nanotubes (CNTs) lag far behind their 2D CNT-based bricks and require major improvements for biological applications. By using Fe nanoparticles confined to the interlamination of graphite as catalyst, a fully 3D interconnected CNT web is obtained through the pores of graphene foam (GCNT web) by in situ chemical vapor deposition. This 3D GCNT web has a thickness up to 1.5 mm and a completely geometric, mechanical and electrical interconnectivity. Dissociated cortical cells cultured inside the GCNT web form a functional 3D cortex-like network exhibiting a spontaneous electrical activity that is closer to what is observed in vivo. By coculturing and fluorescently labeling glioma and healthy cortical cells with different colors, a new in vitro model is obtained to investigate malignant glioma infiltration. This model allows the 3D trajectories and velocity distribution of individual infiltrating glioma to be reconstructed with an unprecedented precision. The model is cost effective and allows a quantitative and rigorous screening of anticancer drugs. The fully 3D interconnected GCNT web is biocompatible and is an ideal tool to study 3D biological processes in vitro representing a pivotal step toward precise and personalized medicine.


Assuntos
Neoplasias Encefálicas , Córtex Cerebral , Glioma , Grafite , Nanotubos de Carbono , Alicerces Teciduais , Animais , Bioengenharia/métodos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular , Células Cultivadas , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Técnicas de Cocultura , Glioma/patologia , Glioma/fisiopatologia , Grafite/química , Humanos , Nanotubos de Carbono/química , Invasividade Neoplásica/fisiopatologia , Neurônios/patologia , Neurônios/fisiologia , Níquel/química , Ratos Wistar , Transmissão Sináptica
20.
ACS Appl Mater Interfaces ; 8(50): 34227-34233, 2016 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-27998102

RESUMO

Physical cues of the scaffolds, elasticity, and stiffness significantly guide adhesion, proliferation, and differentiation of stem cells. In addressable microenvironments constructed by three-dimensional graphene foams (3D-GFs), neural stem cells (NSCs) interact with and respond to the structural geometry and mechanical properties of porous scaffolds. Our studies aim to investigate NSC behavior on the various stiffness of 3D-GFs. Two kinds of 3D-GFs scaffolds present soft and stiff properties with elasticity moduli of 30 and 64 kPa, respectively. Stiff scaffold enhanced NSC attachment and proliferation with vinculin and integrin gene expression were up-regulated by 2.3 and 1.5 folds, respectively, compared with the soft one. Meanwhile, up-regulated Ki67 expression and almost no variation of nestin expression in a group of the stiff scaffold were observed, implying that the stiff substrate fosters NSC growth and keeps the cells in an active stem state. Furthermore, NSCs grown on stiff scaffold exhibited enhanced differentiation to astrocytes. Interestingly, differentiated neurons on stiff scaffold are suppressed since growth associated protein-43 expression was significantly improved by 5.5 folds.


Assuntos
Grafite , Células-Tronco Neurais/citologia , Alicerces Teciduais , Animais , Astrócitos/citologia , Adesão Celular/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Hipocampo/citologia , Camundongos , Camundongos Endogâmicos ICR , Neurônios/citologia
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