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1.
J Mater Chem B ; 9(45): 9370-9382, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34726686

RESUMO

Injectable cell-based hydrogels allow surgical operation in a minimally invasive way for articular cartilage lesions but the chondrocytes in the injectable hydrogels are difficultly arrayed and fixed at the site of interest to repair the cartilage tissue. In this study, an injectable hyaluronic acid-polyacrylic acid (HA-pAA) hydrogel was first synthesized using hyaluronic acid-cyclodextrin (HA-CD) and polyacrylic acid-ferrocene (pAA-Fc) to provide cell-delivery and self-healing. To promote the cell fixation and alignment, porous poly(lactic-co-glycolic acid) (PLGA) magnetic microcapsules (PPMMs) with glutathione (GSH) loaded and iron oxide nanoparticles (IO) located in the shell were designed. The GSH-loaded PPMMs with layer-by-layer (LbL) assembly of hyaluronic acid (HA) and GSH (LbL-PPMMs) can provide a two-stage rapid and slow release of GSH to modulate the self-healing of the HA-pAA hydrogel at the injured site. Furthermore, the chondrocytes embedded in the HA-pAA hydrogel could be delivered through CD44 receptors on the HA polymer chains of LbL-PPMMs toward the surface of the damaged site by an internal magnetic force. The composite hydrogel system of chondrocytes/LbL-PPMMs/HA-pAA can provide the damaged cartilage with a more even and smooth surface than other groups in a rabbit model after 8 weeks of implantation. In addition, the chondrocytes in the deep zone tissue exhibit a columnar array, similar to the cell arrangement in normal cartilage tissue. Together with the cell navigation behavior and GSH release from the LbL-PPMM/HA-pAA hydrogel, a full closure of lesions on the cartilage tissue can be achieved. Our results demonstrate the highly promising potential of the injectable LbL-PPMM/HA-pAA system in cartilage tissue repair.

2.
J Am Chem Soc ; 143(40): 16512-16518, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34601870

RESUMO

Heterojunction nanostructures usually exhibit enhanced properties in compariosn with their building blocks and are promising catalyst candidates due to their combined surface and unique interface. Here, for the first time we realized the oriented growth of ultrasmall metal nanoparticles (NPs) on metal-organic framework nanosheets (MOF NSs) by precisely regulating the reduction kinetics of metal ions with solvents. In particular, a rapid reduction of metal ions leads to the random distribution of metal NPs on the surface of MOF NSs, while a slow reduction of metal ions results in the oriented growth of NPs on the edge of MOF NSs. Impressively, the strong synergy between Pt NPs and MOF NSs significantly enhances the hydrogen evolution reaction (HER) performance, and the optimal catalyst displays HER activities superior to those of a composite with a random growth of Pt NPs and commercial Pt/C under both acidic and alkaline conditions. Moreover, the versatility of such oriented growth has been extended to other metal NPs, such as Pd, Ag, and Au. We believe this work will promote research interest in material design for many potential applications.

3.
Nanomaterials (Basel) ; 11(9)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34578551

RESUMO

Radiotherapy (RT), in combination with surgery, is an essential treatment strategy for oral cancer. Although irradiation provides effective control over tumor growth, the surrounding normal tissues are almost inevitably affected. With further understanding of the molecular mechanisms involved in radiation response and recent advances in nanotechnology, using gold nanoparticles as a radiosensitizer provides the preferential sensitization of tumor cells to radiation and minimizes normal tissue damage. Herein, we developed gold nano-sesame-beads (GNSbs), a gold-nanorod-seeded mesoporous silica nanoparticle, as a novel radioenhancer to achieve radiotherapy with a higher therapeutic index. GNSbs in combination with 2 Gy irradiation effectively enhanced the cytotoxic activity CAL-27 cells. The well-designed structure of GNSbs showed preferential cellular uptake by CAL-27 cells at 24 h after incubation. Gold nanorods with high density modified on mesoporous silica nanoparticles resulted in significant reactive oxygen species (ROS) formation after irradiation exposure compared with irradiation alone. Furthermore, GNSbs and irradiation induced more prominent DNA double-strand breaks and G2/M phase arrest in CAL-27 than those in L929. In animal studies, radiotherapy using GNSbs as a radiosensitizer showed significant suppression of tumor growth in an orthotopic model of oral cancer. These results demonstrate that using GNSbs as a radiosensitizer could possess clinical potential for the treatment of oral squamous carcinoma.

4.
Carbohydr Polym ; 273: 118560, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560971

RESUMO

The film-forming process of chitosan composite films is an important issue because it affects their experimental design, chemicals used, and feasibility of large-scaled fabrication. In this work, electrophoresis is employed to produce chitosan composite films with significantly reduced processing time and environmentally friendly chemicals. With the addition of hydrogen peroxide and polyethylene glycol, the parasitic hydrogen bubble formation during the electrophoresis of chitosan and polydopamine is effectively inhibited that leads to the formation of a defectless chitosan/polyethylene glycol/polydopamine composite film which could be removed from the substrate readily. In addition, the chitosan/polyethylene glycol/polydopamine composite film reveals significantly improved tensile strength and a slower decomposition rate as compared to those of chitosan film and chitosan/polyethylene glycol composite film. This is attributed to the strong interaction between chitosan and polydopamine. Lastly, the chitosan/polyethylene glycol/polydopamine composite film exhibits excellent UV-shielding ability without compromising its visible transparency.

5.
J Mater Chem B ; 9(33): 6634-6645, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34365493

RESUMO

Cell alignment and elongation, which are critical factors correlated with differentiation and maturation in cell biology and tissue engineering, have been widely studied in organisms. Several strategies such as external mechanical strain, geometric topography, micropatterning approaches, and microfabricated substrates have been developed to guide cell alignment, but these methodologies cannot be used for easily denatured natural proteins to modulate the cell behaviour. Herein, for the first time, a novel biocompatible light-controlled protein-based bilayer soft actuator composed of elastin-like polypeptides (ELPs), silk fibroin (SF), graphene oxide (GO), and reduced graphene oxide (rGO), named ESGRG, is developed for efficiently driving cellular orientation and elongation with anisotropic features on soft actuator via remote NIR laser exposure. The actuation of ESGRG could be manipulated by modulating the intensity of NIR and the relative ratio of GO to rGO for promoting myoblasts alignment and nucleus elongation to generate different motions. The results indicate that the YAP and MHC protein expression of C2C12 skeletal muscle cells on ESGRG can be rapidly induced and enhanced by controlling the relative ratio of rGO/GO = 1/4 at a multiple-cycle stimulation with a very low power intensity of 1.2 W cm-2 in friendly liquid environments. This study demonstrates that the ESGRG hydrogel actuator system can modulate the cell-level behaviors via light-driven cyclic bending-motions and can be utilized in applications of soft robotic and tissue engineering such as artificial muscle and maturation of cardiomyocytes.

6.
Sci Rep ; 11(1): 9610, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953260

RESUMO

We demonstrated the design of pre-additive manufacturing microalloying elements in tuning the microstructure of iron (Fe)-based alloys for their tunable mechanical properties. We tailored the microalloying stoichiometry of the feedstock to control the grain sizes of the metallic alloy systems. Two specific microalloying stoichiometries were reported, namely biodegradable iron powder with 99.5% purity (BDFe) and that with 98.5% (BDFe-Mo). Compared with the BDFe, the BDFe-Mo powder was found to have lower coefficient of thermal expansion (CTE) value and better oxidation resistance during consecutive heating and cooling cycles. The selective laser melting (SLM)-built BDFe-Mo exhibited high ultimate tensile strength (UTS) of 1200 MPa and fair elongation of 13.5%, while the SLM-built BDFe alloy revealed a much lower UTS of 495 MPa and a relatively better elongation of 17.5%, indicating the strength enhancement compared with the other biodegradable systems. Such an enhanced mechanical behavior in the BDFe-Mo was assigned to the dominant mechanism of ferrite grain refinement coupled with precipitate strengthening. Our findings suggest the tunability of outstanding strength-ductility combination by tailoring the pre-additive manufacturing microalloying elements with their proper concentrations.

7.
Biomaterials ; 271: 120762, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33773400

RESUMO

Although traditional 3D scaffolds or biomimetic hydrogels have been used for tissue engineering and regenerative medicine, soft tissue microenvironment usually has a highly anisotropic structure and a dynamically controllable deformation with various biomolecule distribution. In this study, we developed a hierarchical hybrid gelatin methacrylate-microcapsule hydrogel (HGMH) with Neurotrophin-3(NT-3)-loaded PLGA microcapsules to fabricate anisotropic structure with patterned NT-3 distribution (demonstrated as striped and triangular patterns) by dielectrophoresis (DEP). The HGMH provides a dynamic biomimetic sinuate-microwrinkles change with NT-3 spatial gradient and 2-stage time-dependent distribution, which was further simulated using a 3D finite element model. As demonstrated, in comparison with striped-patterned hydrogel, the triangular-patterned HGMH with highly anisotropic array of microcapsules exhibits remarkably spatial NT-3 gradient distributions that can not only guide neural stem cells (NSCs) migration but also facilitate spinal cord injury regeneration. This approach to construct hierarchical 4D hydrogel system via an electromicrofluidic platform demonstrates the potential for building various biomimetic soft scaffolds in vitro tailed to real soft tissues.


Assuntos
Hidrogéis , Regeneração da Medula Espinal , Cápsulas , Engenharia Tecidual , Tecidos Suporte
8.
Dyes Pigm ; 1892021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33746312

RESUMO

A novel aggregation-induced emission (AIE) structure containing a tetraphenylethene (TPE) unit covalently linked with a merocyanine (MC) unit was synthesized and investigated in semi-aqueous solutions with 90% water fraction. The open-form structure of red-emissive MC unit combined with TPE unit was utilized as a bi-fluorophoric sensor to detect lead(II) ion, which could be transformed from the close-form structure of non-emissive SP unit upon UV exposure. Moreover, the TPE unit as an energy donor with the blue-green photoluminescence (PL) emission at 480 nm was combined with the MC unit as an energy acceptor with the red PL emission at 635 nm. Due to the Förster resonance energy transfer (FRET) processes, the bi-fluorophoric sensor produced more efficient ratiometric PL behavior to induce a stronger red PL emission than that of the mono-fluorophoric MC unit. Hence, the PL sensor responses of the AIE bi-fluorophoric structure toward lead(II) ion could be further amplified via the FRET-OFF processes to turn off red PL emission of the coordinated MC acceptor and to recover blue-green PL emission of the TPE donor. Accordingly, the best LOD value for the AIE sensor detection toward Pb2+ was 0.27 µM. The highest red MC emission with the optimum FRET process of AIE sensor could be utilized in cell viability tests to prove the non-toxic and remarkable bio-marker of AIE sensor to detect lead(II) ion in live cells. The developed FRET-OFF processes with ratiometric PL behavior of the bi-fluorophoric AIE sensor can be utilized for future chemo- and bio-sensor applications.

9.
Adv Healthc Mater ; 10(1): e2001451, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135398

RESUMO

Cancer immunotherapy is a cutting-edge strategy that eliminates cancer cells by amplifying the host's immune system. However, the low response rate and risks of inducing systemic toxicity have raised uncertainty in the treatment. Magnetic nanoparticles (MNPs) as a versatile theranostic tool can be used to target delivery of multiple immunotherapeutics and monitor cell/tissue responses. These capabilities enable the real-time characterization of the factors that contribute to immunoactivity so that future treatments can be optimized. The magnetic properties of MNPs further allow the implementation of magnetic navigation and magnetic hyperthermia for boosting the efficacy of immunotherapy. The multimodal approach opens an avenue to induce robust immune responses, minimize safety issues, and monitor immune activities simultaneously. Thus, the object of this review is to provide an overview of the burgeoning fields and to highlight novel technologies for next-generation immunotherapy. The review further correlates the properties of MNPs with the latest treatment strategies to explore the crosstalk between magnetic nanomaterials and the immune system. This comprehensive review of MNP-derived immunotherapy covers the obstacles and opportunities for future development and clinical translation.


Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Neoplasias , Humanos , Magnetismo , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/terapia , Medicina de Precisão
10.
Eur J Pharmacol ; 892: 173756, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33245897

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a poor prognosis. The current treatment regimen, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, is still not curative. Therefore, there is an emerging need to develop a drug to treat GBM or synergistic enhance TMZ effect on GBM cells. Flunarizine (FLN), a drug approved for treating migraine and vertigo, was analyzed for its cytotoxicity and synergistic effect with TMZ on GBM cells in this study. Cell proliferation, clonogenic assay, flow cytometry, and Western blotting were used to determine the effects of FLN on three GBM cells, U-87 MG, LN-229, and U-118 MG cells. We found that FLN induced GBM cell death. FLN also interfered with U-87 MG cell cycle progression. Flow cytometric analysis showed an increase of apoptotic cells after FLN treatment. Caspase 9, caspase 3, and Poly (ADP-ribose) polymerase (PARP) activation were involved in apoptosis induction in U-87 MG and LN-229, suggesting the possible involvement of an intrinsic apoptotic pathway. We found that FLN treatment inhibited Akt pathway activation in U-87 MG cells, and synergistically increased the cytotoxicity of three GBM cells when combined with TMZ treatment. In conclusion, our current data suggested that FLN inhibited cell viability by inducing apoptosis. FLN inhibited Akt activation and enhanced the sensitivity of GBM cells to TMZ. These findings may provide important information regarding the application of FLN in GBM treatment in the future.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Flunarizina/farmacologia , Glioblastoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Temozolomida/farmacologia
11.
J Control Release ; 329: 136-147, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33278482

RESUMO

Serious side effects from chemotherapies are the main problem with cancer treatments. To solve these issues, precision cancer nanomedicine based on natural therapeutic materials is developed, which enables specifically apoptosis by interacting with genetic mutation in cancer cells, while leaving normal cells unaffected. Here, we report a novel nanomedicine (CuQDA/IO@HA) composed of hyaluronic acid (HA) / copper ion (Cu(II))-chelated dextran-aldehyde (DA)-quercetin (Q) with dual targeting for synthetic lethal therapy. The CuQDA/IO@HA prepared using a ratio of metal/Q at 0.5:1 resulted in a stable particle structure with uniform particle distribution. The CuQDA/IO@HA can specifically target and induce specific cytotoxicity in BRCA-mutant cancer cells in vitro. Combination treatment with CuQDA/IO@HA and magnetic navigation can induce poly (ADP-ribose) polymerase (PARP) inhibition and DNA damage in BRCA-mutant triple-negative breast cancer (TNBC) via CD44 targeting. The dual-targeting CuQDA/IO@HA can extend the median survival of the BRCA-mutant xenograft mice from 34 to 61 days in comparison to Q treatment alone in vivo, which is attributed to the significant increase in γH2AX, leading to significant apoptosis. More importantly, the CuQDA/IO@HA displayed biocompatibility and no obvious side-effect in normal organs. These results demonstrate the promising potential of integrating natural and metal ions into a nanomedicine that can provide precision medicine through synthetic lethality.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Dextranos , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Camundongos , Nanomedicina , Inibidores de Poli(ADP-Ribose) Polimerases , Quercetina/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
12.
Anticancer Res ; 40(12): 6907-6914, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288584

RESUMO

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Resistance to chemotherapy and side-effects remain a challenge for treating advanced and recurrent HCC. Therefore, there is an emerging need to develop new drugs to treat HCC. MATERIALS AND METHODS: We evaluated the anti-growth activity of flavopereirine in HepG2 and Huh7 HCC cell lines. Cell viability, cell-cycle profile, apoptosis, and autophagy-related protein expressions were analysed after flavopereirine treatment. RESULTS: Flavopereirine treatment induced G0/G1 cell-cycle arrest, with an increase of sub-G1 cells detected at the higher concentration and longer exposure to flavopereirine in HCC cells. Intrinsic and extrinsic pathways were involved in flavopereirine-induced apoptosis, as demonstrated by an increase of cleaved caspase 8 and 9 by western blotting. An alteration of autophagy-related protein expression was also found after flavopereirine treatment. CONCLUSION: Taken together, the current results indicate that flavopereirine exhibits good anticancer activity in HCC cells.


Assuntos
Antineoplásicos/farmacologia , Proteínas Relacionadas à Autofagia/genética , Carbolinas/farmacologia , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/genética , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo
13.
Int J Mol Sci ; 21(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050160

RESUMO

In this study, we optimized the geometry and composition of additive-manufactured pedicle screws. Metal powders of titanium-aluminum-vanadium (Ti-6Al-4V) were mixed with reactive glass-ceramic biomaterials of bioactive glass (BG) powders. To optimize the geometry of pedicle screws, we applied a novel numerical approach to proposing the optimal shape of the healing chamber to promote biological healing. We examined the geometry and composition effects of pedicle screw implants on the interfacial autologous bone attachment and bone graft incorporation through in vivo studies. The addition of an optimal amount of BG to Ti-6Al-4V leads to a lower elastic modulus of the ceramic-metal composite material, effectively reducing the stress-shielding effects. Pedicle screw implants with optimal shape design and made of the composite material of Ti-6Al-4V doped with BG fabricated through additive manufacturing exhibit greater osseointegration and a more rapid bone volume fraction during the fracture healing process 120 days after implantation, per in vivo studies.


Assuntos
Alumínio , Desenvolvimento Ósseo , Vidro , Parafusos Pediculares , Pós , Próteses e Implantes , Titânio , Vanádio , Animais , Fenômenos Biomecânicos , Remodelação Óssea , Processamento de Imagem Assistida por Computador , Osseointegração , Estresse Mecânico , Suínos , Tomografia Computadorizada por Raios X
14.
Dent Mater ; 36(11): 1437-1451, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32962852

RESUMO

OBJECTIVE: Our aim is to examine the mechanical properties of two types of additive manufactured hollow porous dental implants and 6 and 12-week bone ingrowth after insertion in animals. A 3D numerical model is also developed to show detailed tissue differentiation and to provide design guidelines for implants. METHODS: The two porous and a commercial dental implant were studied by series of in vitro mechanical tests (three-point bending, torsional, screwing torque, and sawbone pull-out tests). They also evaluated by in vivo animal tests (micro-CT analysis) and ex vivo pull-out tests. Moreover, the mechano-regulation algorithm was implemented by the 3D finite element model to predict the history of tissue differentiation around the implants. RESULTS: The results showed that the two porous implants can significantly improve osseointegration after 12-week bone healing. This resulted in good fixation and stability of implants, giving very high maximum pull-out strength 413.1 N and 493.2 N, compared to 245.7 N for the commercial implant. Also, several features were accurately predicted by the mechano-regulation model, such as transversely connected bone formation, and bone resorption occurred in the middle of implants. SIGNIFICANCE: Systematic studies on dental implants with multiple approaches, including new design, mechanical tests, animal tests, and numerical modeling, were performed. Two hollow porous implants significantly improved bone ingrowth compared with commercial implants, while maintaining mechanical strength. Also, the numerical model was verified by animal tests. It improved the efficiency of design and reduce the demand for animal sacrifice.


Assuntos
Implantes Dentários , Animais , Osseointegração , Osteogênese , Porosidade , Titânio , Microtomografia por Raio-X
15.
Biomolecules ; 10(7)2020 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-32605162

RESUMO

Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side effect can be achieved to amplify the therapeutic efficacy. In this study, a novel type of fucoidan-PLGA nanocarrier (FPN-DTX) was developed for the encapsulation of the hydrophobic anticancer drug, docetaxel (DTX), as a drug delivery system. From the comparison between FPN-DTX and the PLGA particles without fucoidan (PLGA-DTX), FPNs-DTX with fucoidan were highly stable with smaller sizes and dispersed well without aggregations in an aqueous environment. The drug loading and release can be further modified by modulating relative ratios of Fucoidan (Fu) to PLGA. The (FPN 3-DTX) nanoparticles with a 10:3 ratio of Fu:PLGA displayed uniform particle size with higher encapsulation efficiency than PLGA NPs and sustained drug release ability. The biocompatible fucoidan-PLGA nanoparticles displayed low cytotoxicity without drug loading after incubation with MDA-MB-231 triple-negative breast cancer cells. Despite lower cellular uptake than that of PLGA-DTX due to a higher degree of negative zeta potential and hydrophilicity, FPN 3-DTX effectively exerted better anticancer ability, so FPN 3-DTX can serve as a competent drug delivery system.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Polissacarídeos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Docetaxel/química , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Feminino , Humanos , Nanopartículas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/farmacologia
16.
J Mater Chem B ; 8(25): 5460-5471, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32462165

RESUMO

Metastasis resulting from circulating tumor cells (CTCs) is associated with 90% of all cancer mortality. To disrupt cancer dissemination, therapeutic targeting of CTCs by extracorporeal photodynamic therapy (PDT) has emerged; however, it still remains impractical due to its limited therapeutic window. Herein, we developed a photosensitive and magnetic targeted core-satellite nanomedicine (TCSN) to augment the light-induced damage to the targeted cells. The magnetic nanocore (MNC) with multiple iron oxide nanoparticles stabilized using thiolated polyvinyl alcohol can magnetize the CTCs to achieve magnetic enrichment under a magnetic field. Multiple gold nanocage (AuNC) satellites were conjugated on the MNC to facilitate bimodal photothermal therapy and PDT. Adjusting the thiol content in the MNC allows manipulating the AuNC density on TCSNs, which has been found to demonstrate a density-dependent bimodal phototherapeutic effect under laser irradiation at 808 and 940 nm. Moreover, with the immobilization of anti-epithelial cell adhesion molecule (anti-EpCAM), TCSN exhibited an enhanced affinity toward EpCAM-expressing 4T1 cells. We demonstrate that TCSN-labeled 4T1 cells can be isolated and photo-eradicated in a microfluidic channel with a dynamic flow. Our studies showed that TCSN with the complementary properties of MNC and AuNCs can largely augment the therapeutic window by magnetic enrichment and bimodal phototherapy, serving as an advanced extracorporeal strategy to remove CTCs.


Assuntos
Ouro/farmacologia , Nanopartículas Metálicas/química , Células Neoplásicas Circulantes/efeitos dos fármacos , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ouro/química , Lasers , Campos Magnéticos , Camundongos , Nanomedicina , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Propriedades de Superfície
17.
Int J Mol Sci ; 21(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455543

RESUMO

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.


Assuntos
Parafusos Ósseos/normas , Osseointegração , Impressão Tridimensional , Tendões/cirurgia , Tíbia/cirurgia , Ligas/química , Animais , Parafusos Ósseos/efeitos adversos , Interface Osso-Implante/cirurgia , Fosfatos de Cálcio/química , Porosidade , Coelhos
18.
Polymers (Basel) ; 12(4)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252253

RESUMO

Articular cartilage defect is a common disorder caused by sustained mechanical stress. Owing to its nature of avascular, cartilage had less reconstruction ability so there is always a need for other repair strategies. In this study, we proposed tissue-mimetic pellets composed of chondrocytes and hyaluronic acid-graft-amphiphilic gelatin microcapsules (HA-AGMCs) to serve as biomimetic chondrocyte extracellular matrix (ECM) environments. The multifunctional HA-AGMC with specific targeting on CD44 receptors provides excellent structural stability and demonstrates high cell viability even in the center of pellets after 14 days culture. Furthermore, with superparamagnetic iron oxide nanoparticles (SPIOs) in the microcapsule shell of HA-AGMCs, it not only showed sound cell guiding ability but also induced two physical stimulations of static magnetic field(S) and magnet-derived shear stress (MF) on chondrogenic regeneration. Cartilage tissue-specific gene expressions of Col II and SOX9 were upregulated in the present of HA-AGMC in the early stage, and HA-AGMC+MF+S held the highest chondrogenic commitments throughout the study. Additionally, cartilage tissue-mimetic pellets with magnetic stimulation can stimulate chondrogenesis and sGAG synthesis.

19.
J Formos Med Assoc ; 119(1 Pt 3): 420-429, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31387841

RESUMO

BACKGROUND/PURPOSE: Alveolar bone loss following peri-implantitis remains a clinical challenge. We aimed to design a novel bioactive dental implant to accommodate the large bone defect caused by removal of previously failed implant. METHODS: Bio-ActiveITRI dental implant was manufactured with laser-sintered additive 3D printing technique. A 7.5 mm diameter × 7.0 mm depth osteotomy defect was created at the lateral aspect of distal femur of 20 New Zealand white rabbits to simulate the bony defect after removal of failed dental implant. One side of distal femurs was randomly selected for the commercially pure titanium NobelActive™ implant (control group) and the other side with Bio-ActiveITRI Ti6Al4V porous dental implant (ITRI group). Animals were sacrificed at 4, 8 and 12 weeks after the implants' insertion. The samples were processed for gross morphological analysis, radiographic examination, micro-CT evaluation, and mechanical testing. RESULTS: In histomorphometrical evaluation and micro-CT analysis, active new bone formation and good osseointegration within the ITRI implants were observed at the bone gap surrounding the dental implants. The biomechanical parameters in the Bio-ActiveITRI dental implants were significantly higher than those of the commercially control samples. For the Bio-ActiveITRI dental implants, the trabecular thickness decreased, while the trabecular separation and total porosity increased from the prescribed 1-month to 3-month time points; reflecting the natural remodeling of surrounding bony tissue in the Bio-ActiveITRI dental implants. CONCLUSION: The novel porous structured Bio-ActiveITRI dental implants may have a great potential for the prosthetic reconstruction where bone support is compromised after removal of a previously failed implant.


Assuntos
Implantes Dentários , Fêmur/cirurgia , Lasers , Osseointegração/fisiologia , Impressão Tridimensional , Titânio/química , Animais , Teste de Materiais , Porosidade , Coelhos , Propriedades de Superfície , Titânio/efeitos da radiação , Microtomografia por Raio-X
20.
ACS Biomater Sci Eng ; 6(2): 1144-1153, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33464846

RESUMO

Effective integration of stimulation and direction in bionic scaffolds by materials and microstructure design has been the focus in the advancement of nerve regeneration. Hydrogels are the most promising biomimicked materials used in developing nerve grafts, but the highly hydrated networks limit the fabrication of hydrogel materials into complex biomedical devices. Herein, facile lithography-free and spontaneously micropatterned techniques were used to fabricate a smart protein hydrogel-based scaffold, which carried topographical, electrical, and chemical induction for neural regulation. The synthesized tissue-mimicked silk-gelatin (SG)/polylactic acid bilayer system can self-form three-dimensional ordered corrugation micropatterns with well-defined dimensions (wavelength, λ) based on the stress-induced topography. Through magnetically and topographically guided deposition of the synthesized nerve growth factor-incorporated Fe3O4-graphene nanoparticles (GFPNs), a biologically and electrically conductive cell passage with one-dimensional directionality was constructed to allow for a controllable constrained geometric effect on neuronal adhesion, differentiation, and neurite orientation. Particularly, the SG with corrugation patterns of λ ≈ 30 µm resulted in the optimal cell adhesion and differentiation in response to the pattern guidance. Furthermore, the additional electrical stimulation applied on GFPN-deposited SG resulted in a 1.5-fold increase in the neurite elongation by day 7, finally leading to the neuronal connection by day 21. Such a hydrogel device with synergistic effects of physical and chemical enhancement on neuronal activity provides an expectable opportunity in the development of next-generation nerve conduits.


Assuntos
Gelatina , Seda , Condutividade Elétrica , Eletricidade , Hidrogéis
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