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1.
Transl Stroke Res ; 12(5): 844-857, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33067776

RESUMO

Tissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol-crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in the infarct brain tissue, owing to the dynamic crosslink property of PEG-UK. In vivo tests on a thromboembolic stroke rat model showed that the formulations containing UK, i.e., free UK and PEG-UK+UK, demonstrated better neurological scores and smaller infarction volumes within the time window, in which the PEG-UK+UK formulation relatively performed better. On the other hand, the formulations containing PEG-UK, i.e., PEG-UK and PEG-UK+UK, gained sufficient thrombolytic efficiency beyond the time window. Further investigation on the mechanism revealed that PEG-UK could reduce microthrombus in distal microcirculation, and its destructive effect was also less than that of free UK. The PEG-UK+UK formulation actually provided a "dual targeting" delivery of UK to both the large vessels and the microcirculation, which was beneficial to the treatment of cerebral ischemic stroke both within and beyond the therapeutic time window.

2.
J Mater Chem B ; 8(43): 9881-9887, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33001121

RESUMO

Quantum dots (QDs) are increasingly being utilized as near infrared (NIR) active photothermal agents for cancer diagnosis and therapy, with the main emphasis of current research being the enhancement of photothermal conversion efficiencies. Herein, we report the facile synthesis of 2-3 nm boron quantum dots (B QDs), which demonstrated a remarkable photothermal conversion efficiency of 57% under NIR excitation. This outstanding performance can be attributed to the alteration of the electronic structure, which was a result from the distorted edge-effect induced by the unique empty orbit of B atoms in the B QDs. These results can be verified by B K-edge near edge X-ray absorption fine structure (NEXAFS), high-resolution transmission electron microscopy (HR-TEM) and density functional theory (DFT) calculations. The results demonstrate that B QDs represent a promising new and non-toxic agent for both multimodal NIR-driven cancer imaging and photothermal therapy. This work thus identifies B QDs as an exciting new and theranostic agent for cancer therapy. Furthermore, the synthetic strategy used here to synthesize the B QDs was simple and easily scalable.


Assuntos
Boro/uso terapêutico , Neoplasias/terapia , Terapia Fototérmica , Pontos Quânticos/uso terapêutico , Boro/química , Células HeLa , Humanos , Modelos Moleculares , Neoplasias/diagnóstico , Técnicas Fotoacústicas , Pontos Quânticos/química , Nanomedicina Teranóstica
3.
Artigo em Inglês | MEDLINE | ID: mdl-32714919

RESUMO

Periarticular injury usually causes the defects of superficial cartilage and the underlying subchondral bone. Although some efficacious outcomes have been achieved by the existing therapeutic methods both in clinics and research, like symptomatic treatment, microfracture surgery, and tissue engineering technology, they still present specific disadvantages and complications. To improve this situation, we designed a biphasic (bi-) scaffold aiming to repair the structure of cartilage and subchondral bone synchronously. The scaffold consisted of a superior double-network (DN) hydrogel layer and a lower bioactive glass (BG) reinforced hydrogel layer, and the DN hydrogel included glycol chitosan (GC) and dibenzaldhyde functionalized poly(ethylene oxide) network, and sodium alginate (Alg) and calcium chloride (CaCl2) network. To investigate its effectiveness, we applied this biphasic scaffold to repair osteochondral full-thickness defects in rabbit models. We set up six observation groups in total, including Untreated group, Microfracture group, BG only group, DN gel group, bi-DN gel group, and bi-DN/TGF-ß gel group. With a follow-up period of 24 weeks, we evaluated the treatment effects by gross observation, micro-CT scan and histological staining. Besides, we further fulfilled the quantitative analysis of the data from ICRS score, O'Driscoll score and micro-CT parameters. The results revealed that neat GC/Alg DN hydrogel scaffold was only conductive to promoting cartilage regeneration and neat BG scaffold merely showed the excellent ability to reconstruct subchondral bone. While the biphasic scaffold performed better in repairing osteochondral defect synchronously, exhibiting more well-integrated cartilage-like tissue with positive staining of toluidine blue and col II immunohistochemistry, and more dense trabecular bone connecting closely with the surrounding host bone. Therefore, this method possessed the clinical application potential in treating articular injury, osteochondral degeneration, osteochondral necrosis, and sclerosis.

4.
ACS Appl Mater Interfaces ; 12(3): 3445-3452, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31922399

RESUMO

For effective treatment of ischemic cerebral thrombosis, it is of great significance to find a facile way in assessing the early damage of blood-brain barrier (BBB) after ischemic stroke during thrombolysis by integrating thrombolytic agents with fluorescent materials. Herein, a novel type of protein-carbon dot  nanohybrids is reported by the incorporation of carbon dots on thrombolytic agents through covalent linkage. Both in vitro and ex vivo fluorescence imaging measurements have demonstrated remarkable imaging effects in the brain of transient middle cerebral artery occlusion mice. Besides, the outstanding thrombolytic capacity of the nanohybrids was determined by in vitro thrombolysis tests. As one of the few reports of the construction of thrombolytic agents and fluorescent nanomaterials, the nanohybrids retain thrombolysis ability and fluorescent traceability simultaneously. It may provide a promising indicator for early BBB damage and thrombolytic agent distribution to estimate the possibility of symptomatic intracranial hemorrhage after thrombolysis and supply tissue window evidence for clinical thrombolytic agent application.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Carbono/química , Fibrinolíticos/administração & dosagem , Nanoestruturas/química , Acidente Vascular Cerebral/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Animais , Fibrinolíticos/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Acidente Vascular Cerebral/diagnóstico por imagem , Nanomedicina Teranóstica/instrumentação , Ativador de Plasminogênio Tipo Uroquinase/química
5.
ACS Appl Mater Interfaces ; 11(38): 35228-35237, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31479230

RESUMO

In recent years, single-atom catalysts (SACs) have attracted enormous attention due their effectiveness in promoting a variety of catalytic reactions. However, the ability of SACs to enhance cancer phototherapies has received little attention to date. Herein, we synthesized a metal organic framework (MOF) rich in porphyrin-like single atom Fe(III) centers (denoted herein as porphyrin-MOF or P-MOF) and then evaluated the performance of the P-MOF for cancer treatment by photodynamic therapy (PDT) and photothermal therapy (PTT) under NIR (808 nm) irradiation, as well as photoacoustic imaging (PAI) of tumors. On acccount of the abundance of single atom Fe(III) centers, the P-MOF material demonstrated excellent performance for modulation of the hypoxic tumor microenvironment of Hela cell tumors in mice, while also demonstrating good properties as a photoacoustic imaging (PAI) agent. Density functional theory (DFT) calculations were used to elucidate the superior performance of P-MOF in these applications relative to Fe2O3 (a Fe(III) reference compound). The calculations revealed that the narrow band gap energy of P-MOF (1.31 eV) enabled strong absorption of NIR photons, thereby inducing nonradiative transitions that converted incident light into heat to promote PTT. Further, a facile change of the spin state of the single atom Fe(III) centers in P-MOF under NIR irradiation transformed coordinated triplet oxygen (3O2) to singlet oxygen (1O2), benefiting PDT. This work demonstrates the great future potential of both SACs and MOFs as multifunctional agents for cancer treatment and tumor imaging.


Assuntos
Estruturas Metalorgânicas , Modelos Químicos , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Porfirinas , Microambiente Tumoral/efeitos dos fármacos , Células HeLa , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia , Porfirinas/química , Porfirinas/farmacologia
6.
Adv Healthc Mater ; 8(17): e1900709, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31353829

RESUMO

For treating bone defects in periarticular fractures, there is a lack of biomaterial with injectable characteristics, tough structure, and osteogenic capacity for providing a whole-structure support and osteogenesis in the defect area. An injectable hydrogel is an ideal implant, however is weak as load-bearing scaffolds. Herein, a new strategy, i.e., an in situ formation of "active" composite double network (DN), is raised for the preparation of an injectable strong hydrogel particularly against compression. As a demonstration, 4-carboxyphenylboronic acid grafted poly(vinyl alcohol) (PVA) is crosslinked using calcium ions to provide a tough frame while bioactive glass (BG) microspheres are associated by poly(ethylene glycol) to obtain an interpenetrated inorganic network for reinforcement. The injected PVA/BG DN hydrogel gains compressive strength, modulus, and fracture energy of 34 MPa, 0.8 MPa, and 40 kJ m-2 , respectively. Then, the properties can be "autostrengthened" to 57 MPa, 2 MPa, and 65 kJ m-2 by mineralization in 14 days. In vivo experiments prove that the injected DN hydrogel is more efficient to treat femoral supracondylar bone defects than the implanted bulk DN gel. The work suggests a facile way to obtain a strong hydrogel with injectability, cytocompatibility, and tailorable functionality.


Assuntos
Osso e Ossos/fisiologia , Hidrogéis/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Linhagem Celular , Vidro , Injeções , Camundongos , Polietilenoglicóis/química , Álcool de Polivinil , Microtomografia por Raio-X
7.
Chem Sci ; 10(8): 2336-2341, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30881661

RESUMO

Oxygen vacancy (OV) engineering in semiconductors can greatly enhance the separation of photo-induced electron-hole pairs, thereby enhancing the photocatalytic activity. Taking inspiration from this, we prepared a novel BiOBr-H/Rub2d composite by functionalizing OV-rich BiOBr (named BiOBr-H) with a carboxyl functionalized ruthenium photosensitizer (Ru(bpy)2C-pyCl2, abbreviated as Rub2d), which was then successfully applied for photodynamic therapy (PDT). Density functional theory (DFT) calculations confirmed efficient electron transfer from the Rub2d complex to the intermediate energy level of BiOBr-H under visible light irradiation. In vitro and in vivo studies demonstrated that BiOBr-H/Rub2d was a superior agent for photodynamic therapy compared with the free ruthenium complex. The theoretical and experimental data presented thus reveal for the first time that abundant OVs in BiOBr-H can significantly improve the photocatalytic activity of a photosensitizer, resulting in the generation of more reactive oxygen species to enhance PDT. The findings of this study thus offer a new strategy for the development of highly efficient cancer therapies.

8.
J Mater Chem B ; 7(11): 1920-1925, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255054

RESUMO

Okara is a by-product of tofu manufacturing and is usually used as a feedstuff. Herein, we developed a methodology of using okara as a carbon source for the preparation of photothermal nano-materials. It's interesting to find that just after calcination, the carbonized okara forms sphere-shaped hollow particles (denoted as HCNS) with an average diameter of 200 nm. Owning to the existence of a cavity, the HCNS was found to exhibit not only a good photothermal conversion efficiency, but also an ideal photoacoustic imaging property, which makes it a promising agent for imaging-guided photothermal therapy (PTT). The high photothermal conversion efficiency can result from the high carbon content and its hollow morphology. The in vitro and in vivo results both demonstrated the biocompatibility and capacity of the plant source carbon spheres for NIR-triggered cancer treatment. Therefore, the current work suggests a new method to gain a safe and low-cost photothermal platform which could be further exploited in biomedical fields.


Assuntos
Carbono/química , Nanosferas/uso terapêutico , Neoplasias/terapia , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Materiais Biocompatíveis/uso terapêutico , Células HeLa , Células Hep G2 , Humanos , Hipertermia Induzida , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Plantas/química , Polissacarídeos/química , Alimentos de Soja
9.
J Biomed Mater Res A ; 106(12): 3222-3230, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30289606

RESUMO

The aim of this study was to investigate the suppression of inflammation and enhancement of osteogenesis using chitosan-coated calcium hydroxide-loaded microcapsules (CS-EC@Ca microcapsules) in vivo. Circular defects were created in the mandibular bones of rabbits and filled with Ca(OH)2 , Bio-oss, or CS-EC@Ca microcapsules, and rabbits without drug implantation served as the controls. Lipopolysaccharides were injected in situ daily in all groups for 7 days. Mandibular bones were investigated at 4 and 12 weeks after surgery using micro-CT, histological observations, and real-time PCR analysis. At the postoperation, there was more substantial nascent bone in the microcapsule and Bio-oss groups than in the control group. The recovery of the rabbits in the Ca(OH)2 group was slower than the control group, as determined using micro-CT and histological staining. Osteocalcin and collagen type I production was not significantly different between the microcapsule and Bio-oss groups (p > 0.05), but the expression levels of the two molecules were significantly increased compared to the control and Ca(OH)2 groups at postoperation (p < 0.05). The mRNA transcript levels of inflammatory factors in the microcapsule group had the most reduced expression of IL-6 and TNF-α (p < 0.05). The microcapsules significantly reduced inflammation and promoted osteogenesis in this rabbit model of inflammatory bone destruction. Our findings indicate that CS-EC@Ca microcapsules hold potential for use in apical periodontitis treatment. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3222-3230, 2018.


Assuntos
Substitutos Ósseos/uso terapêutico , Hidróxido de Cálcio/uso terapêutico , Quitosana/uso terapêutico , Inflamação/terapia , Traumatismos Mandibulares/terapia , Minerais/uso terapêutico , Animais , Cimentos Ósseos/uso terapêutico , Cápsulas , Implantes de Medicamento/uso terapêutico , Osteogênese/efeitos dos fármacos , Coelhos
10.
Bioact Mater ; 3(1): 102-109, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29744447

RESUMO

The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i.v. dose of free uPA no matter with or without US intervention. Meanwhile, the preservation ability of the nanogels not only prolonged the circulation duration of the protein, but also resulted in the better blood-brain barrier protection of the nUK formulation, showing no increased risk on the hemorrhagic transformation than the controls. This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.

11.
Talanta ; 184: 50-57, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29674075

RESUMO

It is a great challenge to develop multifunctional nanocarriers for cancer diagnosis and therapy. Herein, versatile CDs/ICG-uLDHs nanovehicles for triple-modal fluorescence/photoacoustic/two-photon bioimaging and effective photothermal therapy were prepared via a facile self-assembly of red emission carbon dots (CDs), indocyanine green (ICG) with the ultrathin layered double hydroxides (uLDHs). Due to the J-aggregates of ICG constructed in the self-assembly process, CDs/ICG-uLDHs was able to stabilize the photothermal agent ICG and enhanced its photothermal efficiency. Furthermore, the unique confinement effect of uLDHs has extended the fluorescence lifetime of CDs in favor of bioimaging. Considering the excellent in vitro and in vivo phototherapeutics and multimodal imaging effects, this work provides a promising platform for the construction of multifunctional theranostic nanocarrier system for the cancer treatment.


Assuntos
Carbono/química , Corantes Fluorescentes/química , Hidróxidos/química , Neoplasias/diagnóstico por imagem , Imagem Óptica , Fototerapia , Pontos Quânticos/química , Fluorescência , Humanos , Hidróxidos/síntese química , Neoplasias/terapia
12.
Adv Healthc Mater ; 7(10): e1701123, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29430871

RESUMO

In this work, a novel ruthenium complex loaded monolayer layered double hydroxide (LDH) (denoted as Ru(C-bpy)2 /mLDH) as supramolecular nanosensor is synthesized, which is greatly exclusive to the hypoxic tumor microenvironment. The Ru(C-bpy)2 /mLDH ultrathin sheet displays not only enhanced luminescence lifetime compared to the parent Ru(C-bpy)2 alone, but also improved oxygen responsibility under an excitation of 488 or 800 nm. Moreover, the Ru(C-bpy)2 /mLDH is possessed of two-photon fluorescence imaging ability under the 800 nm irradiation. In addition, the Ru(C-bpy)2 /mLDH can generate singlet oxygen with a high yield (φ∆ ) of 0.28 under the 520 nm irradiation, while the φ∆ of Ru(C-bpy)2 is 0.19. Therefore, the Ru(C-bpy)2 /mLDH can be applied as a supramolecular theranostic agent with light-switchable cancer imaging and photodynamic therapy properties.


Assuntos
Nanoestruturas , Neoplasias Experimentais , Fotoquimioterapia , Compostos de Rutênio , Nanomedicina Teranóstica , Hipóxia Tumoral , Microambiente Tumoral , Animais , Diagnóstico por Imagem , Células HeLa , Humanos , Medições Luminescentes , Camundongos , Camundongos Nus , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Compostos de Rutênio/síntese química , Compostos de Rutênio/química , Compostos de Rutênio/farmacologia , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Mater Chem B ; 6(9): 1351-1358, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32254420

RESUMO

In this work, we developed a very facile strategy, i.e. dual dynamic crosslinking, to prepare a high performance injectable hydrogel. Poly(vinyl alcohol) (PVA) was crosslinked by 4-carboxyphenylboronic acid (CPBA) through the generation of borate bonding and ionic interaction to bridge the polymer chains in the presence of calcium ions. The dynamic gathering of CPBA could induce a self-reinforcing effect inside the hydrogel matrix, leading to high tensile and compressive moduli of the hydrogel over 1.0 MPa including the highest compressive modulus up to 5.6 MPa. Meanwhile, the mechanical properties of the hydrogel can be broadly and accurately tuned. And owing to the flexible PVA network, the hydrogel is ultra-tough, showing maximum tensile strain, tensile and compressive fracture energies up to 1600%, 600 kJ m-2 and 25 kJ m-2, respectively. Besides, the dynamic bonding overcomes the barriers to forming an injected strong hydrogel, e.g. to obtain a modulus and a fracture energy exceeding 1.0 MPa and 40 kJ m-2, by using a commercial dual-syringe kit under physiological conditions. Such a mild gelation procedure benefits the administration, 3D encapsulation and proliferation of cells of the hydrogels. The application of the PVA hydrogel was demonstrated by effective cartilage repair.

14.
J Mater Chem B ; 6(15): 2315-2322, 2018 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32254570

RESUMO

In this work, we synthesized a hypoxia responsive upconversion nanosensor by the conjugation of oxygen insensitive upconversion carbon dots (CDs) with an oxygen sensitive ruthenium(ii) complex (Rud2b). The CD-Rud2b conjugate was then PEGylated to mediate the formation of nano-sized assemblies of the resultant polymer probe (CD-Ru-mPEG) in aqueous solution. The strategy allows the oxygen sensitive probe (Rud2b) to be excited by NIR irradiation and achieve upconverted emission through the Förster resonance energy transfer process from the CDs. The oxygen sensitivity of the ruthenium moiety was well-preserved in the polymeric aggregates because the PEG chains could prohibit the occurrence of self-quenching that may occur due to the close packing of the probes. Such an upconversion photoluminescence property makes the CD-Ru-mPEG nanosensor work as a biocompatible imaging system to monitor the oxygen level in cells and the hypoxic condition in vivo.

15.
J Mater Chem B ; 6(47): 7811-7821, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255027

RESUMO

The achievement of rapid vascularization in large implanted constructs is a major challenge in the field of bone tissue engineering. Although co-culture of bone-forming cells and vascular endothelial cells (VECs) has been expected to be a way of promoting vascularization during bone formation with a scaffold, there is a lack of detailed knowledge about the direct interactions between two types of stem cells in a three-dimensional (3D) extracellular matrix (ECM). Herein, we report on the use of an injectable cytocompatible double-network (DN) hydrogel to encapsulate, co-culture and subsequently stimulate the angiogenic/osteogenic differentiation of VECs and the human bone marrow mesenchymal stem cells (BM-MSCs), which demonstrates that the direct co-cultured system enables simultaneous enhancement of vascularization and osteogenesis by providing 3D cell-cell communication. Besides, the improved mechanical properties and the injectability of the DN hydrogel allow the delivery, long-time implantation, proliferation and differentiation of stem cells in vivo. Therefore, this study could provide a niche-like native ECM for stem cell survival and the regulation of the differentiation of multiple cell lines which will benefit bone repair.

16.
Nanoscale ; 9(29): 10367-10374, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28702600

RESUMO

A supramolecular nanovehicle, denoted as ICG-DOX/Gd-LDH, was synthesized by the co-intercalation of indocyanine green (ICG) and doxorubicin hydrochloride (DOX) into a gallery of Gd3+-doped-layered double hydroxide (Gd-LDH) such that to achieve a chemo-photothermal synergistic therapeutic agent. The unique structure of Gd-LDH can not only stabilize the photothermal agent ICG to enhance the photothermal efficiency, but also hamper the recombination between electron and holes, leading to the generation of more reactive oxygen species (ROS) under irradiation in the NIR range. Together with the loading capacity of DOX, ICG-DOX/Gd-LDH exhibited excellent combinatorial effects on tumor growth inhibition in both in vitro studies on HeLa cell line and in vivo tests over tumor-bearing mouse models. Moreover, it showed ideal ability for long-term tracing of the carrier distribution via either MRI or fluorescence imaging. Thus, this study indicates that Gd-LDH is a promising platform for the construction of multifunctional formulations, especially theranostic nano-systems for cancer treatment.

17.
Biomacromolecules ; 18(7): 2128-2138, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-28557440

RESUMO

Herein we present a unique method of using dynamic cross-links, which are dynamic covalent bonding and ionic interaction, for the construction of injectable double-network (DN) hydrogels, with the objective of cell delivery for cartilage repair. Glycol chitosan and dibenzaldhyde capped poly(ethylene oxide) formed the first network, while calcium alginate formed the second one, and in the resultant DN hydrogel, either of the networks could be selectively removed. The moduli of the DN hydrogel were significantly improved compared to that of the parent single-network hydrogels and were tunable by changing the chemical components. In situ 3D cell encapsulation could be easily performed by mixing cell suspension to the polymer solutions and transferred through a syringe needle before sol-gel transition. Cell proliferation and mediated differentiation of mouse chondrogenic cells were achieved in the DN hydrogel extracellular matrix.


Assuntos
Transplante de Células/métodos , Células Imobilizadas/transplante , Condrogênese , Hidrogéis , Polietilenoglicóis , Animais , Linhagem Celular , Células Imobilizadas/metabolismo , Hidrogéis/síntese química , Hidrogéis/química , Hidrogéis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia
18.
J Mater Chem B ; 5(13): 2416-2424, 2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264549

RESUMO

In this work, an injectable composite hydrogel was synthesized via a unique way of crosslinking glycol chitosan (GC) with silica nano-particles (SiNP) through non-chemical interactions, and was then applied as a kind of wound dressing. Gelation was achieved through the incorporation of SiNPs with the GC segments in aqueous solution, therefore strictly confining the movement of the solubilized polymer chains. Rheology tests showed that the sol-gel transition and the moduli of the hydrogel were influenced by the composition of the two components, the size of the nano-particles and the conformation of the polymers. Using such a strategy, tissue adhesion properties of GC were well-preserved in the GC/SiNP hydrogel and therefore it gains gluey properties toward biological tissues as demonstrated through the adhesion of two pieces of mouse skin, obtaining a lap-shear stretching force of ca. 90 kPa. This characteristic, together with the injectability, allowed the hydrogel to be administrated directly on the wound site and to fill the wound area. Meanwhile, the hydrogel also works as a carrier of protein and cells. The in situ encapsulation of fibroblasts enabled the promising properties of the GC/SiNP hydrogel to be used for treating full-thickness skin defects in a mouse model, resulting in the favorable growth of hair follicles and microvessels, hence reducing the risk of scar formation.

19.
J Mater Sci Mater Med ; 28(1): 10, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27915402

RESUMO

Beyond promoting hard tissue repairing, bioactive glasses (BGs) have also been proved to be beneficial for wound healing. Nano-scale BGs prepared by sol-gel method were found to have a better performance as they have a larger specific surface area. In this work, bioactive nanoparticles (nBPs) with mean diameter of 12 nm (BP-12) instead of conventional BGs were mixed with gelatin to form an easy-to-use hydrogel as a dressing for skin wound. It was found that the composite of BP-12 and gelatin could form a hydrogel (BP-12/Gel) under 25 °C, which showed pronounced thixotropy at a practically accessible shear rate, therefore become easy to be used for wound cover. In vitro, the composite hydrogel of BP-12 and gelatin had good biocompatibility with the fibroblast cells. In vivo, rapid cutaneous-tissue regeneration and tissue-structure formation within 7 days was observed in the wound-healing experiment performed in rats. This hydrogel is thus a promising easy-to-use wound dressing material.


Assuntos
Bandagens , Fibroblastos/citologia , Gelatina/química , Hidrogéis/química , Nanopartículas/química , Pele/lesões , Células 3T3 , Animais , Materiais Biocompatíveis/química , Biópsia , Linhagem Celular , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Ratos , Regeneração , Reologia , Propriedades de Superfície , Temperatura , Viscosidade , Cicatrização
20.
Chem Asian J ; 11(19): 2633-2641, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27410679

RESUMO

The benzoic imine is a dynamic covalent bond, which is stable around neutral pH value (ca. 7.4), but starts to hydrolyze at the extracellular pH value of solid tumors (ca. 6.5) and rapidly disintegrates at endosome and lysosome pH values (ca. 4.5-6.5). This characteristic is promising for the construction of physiological-pH-responsive materials, such as polymeric micelles, nanoparticles, and hydrogels for pharmaceutical and tissue-engineering applications. This Focus Review summarizes recent progress in the design and synthesis of pH-sensitive materials that contain the benzoic imine bond with biomedical objectives.


Assuntos
Benzoatos/química , Portadores de Fármacos/química , Iminas/química , Doxorrubicina/química , Doxorrubicina/metabolismo , Endossomos/metabolismo , Hidrogéis/química , Concentração de Íons de Hidrogênio , Hidrólise , Lisossomos/metabolismo , Micelas , Nanopartículas/química , Polímeros/química , Porosidade , Engenharia Tecidual
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