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1.
Biomacromolecules ; 19(12): 4554-4564, 2018 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-30350597

RESUMO

Injectable hydrogels have shown great potential in bone tissue engineering. Simvastatin (SIM), a common hypolipidemic drug, has been suggested as a potential agent to promote bone regeneration. However, due to its hydrophobic nature, the compatibility between SIM and hydrogels is rather poor, thereby greatly affecting the drug release behavior, the mechanical properties, and dimensional stability of the hydrogels. Herein, we presented a novel design to entrap SIM in an injectable maltodextrin-based micelle/hydrogel composite system. Maltodextrin-based micelles were prepared to solubilize and encapsulate SIM. The SIM-loaded aldehyde-modified micelles were anchored to the hydrogel network and served as a cross-linker to realize improved mechanical strength of hydrogel, controlled release, and osteogenic capability of SIM. In all, this study demonstrated a strategy to incorporate drug loaded carriers into hydrogels for drug delivery and tissue engineering applications.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Sinvastatina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/uso terapêutico , Micelas , Osteogênese/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Sinvastatina/química
2.
Biomacromolecules ; 16(11): 3508-18, 2015 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-26414083

RESUMO

Self-healing polymeric hydrogels have the capability to recover their structures and functionalities upon injury, which are extremely attractive in emerging biomedical applications. This research reports a new kind of self-healing polypeptide hydrogels based on self-assembly between cholesterol (Chol)-modified triblock poly(L-glutamic acid)-block-poly(ethylene glycol)-block-poly(L-glutamic acid) ((PLGA-b-PEG-b-PLGA)-g-Chol) and ß-cyclodextrin (ß-CD)-modified poly(L-glutamic acid) (PLGA-g-ß-CD). The hydrogel formation relied on the host and guest linkage between ß-CD and Chol. This study demonstrates the influences of polymer concentration and ß-CD/Chol molar ratio on viscoelastic behavior of the hydrogels. The results showed that storage modulus was highest at polymer concentration of 15% w/v and ß-CD/Chol molar ratio of 1:1. The effect of the PLGA molecular weight in (PLGA-b-PEG-b-PLGA)-g-Chol on viscoelastic behavior, mechanical properties and in vitro degradation of the supramolecular hydrogels was also studied. The hydrogels showed outstanding self-healing capability and good cytocompatibility. The multilayer structure was constructed using hydrogels with self-healing ability. The developed hydrogels provide a fascinating glimpse for the applications in tissue engineering.


Assuntos
Ácido Glutâmico/química , Hidrogéis/química , Materiais Biocompatíveis/química , Humanos , Peso Molecular , Poliésteres/química , Polietilenoglicóis/química , Engenharia Tecidual , Alicerces Teciduais , beta-Ciclodextrinas/química
3.
Biomacromolecules ; 15(12): 4495-508, 2014 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-25279766

RESUMO

Injectable hydrogels as an important biomaterial class have been widely used in regenerative medicine. A series of injectable poly(l-glutamic acid)/alginate (PLGA/ALG) hydrogels were fabricated by self-cross-linking of hydrazide-modified poly(l-glutamic acid) (PLGA-ADH) and aldehyde-modified alginate (ALG-CHO). Both the degree of PLGA modification and the oxidation degree of ALG-CHO could be adjusted by the amount of activators and sodium periodate, respectively. The effect of the solid content of the hydrogels and oxidation degree of ALG-CHO on the gelation time, equilibrium swelling, mechanical properties, microscopic morphology, and in vitro degradation of the hydrogels was examined. Encapsulation of rabbit chondrocytes within hydrogels showed viability of the entrapped cells and good biocompatibility of the injectable hydrogels. A preliminary study exhibited injectability and rapid in vivo gel formation, as well as mechanical stability, cell ingrowth, and ectopic cartilage formation. The injectable PLGA/ALG hydrogels demonstrated attractive properties for future application in a variety of pharmaceutical delivery and tissue engineering, especially in cartilage tissue engineering.


Assuntos
Alginatos/química , Cartilagem/química , Ácido Glutâmico/química , Hidrogéis/química , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/química , Sobrevivência Celular , Condrócitos/citologia , Reagentes de Ligações Cruzadas/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Camundongos , Camundongos Nus , Coelhos , Alicerces Teciduais/química
4.
Adv Healthc Mater ; 12(31): e2302293, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37689993

RESUMO

Articular cartilage tissue is incapable of self-repair and therapies for cartilage defects are still lacking. Injectable hydrogels have drawn much attention in the field of cartilage regeneration. Herein, the novel design of nanofiber composite microchannel-containing hydrogels inspired by the tunnel-piled structure of subway tunnels is proposed. Based on the aldehydized polyethylene glycol/carboxymethyl chitosan (APA/CMCS) hydrogels, thermosensitive gelatin microrods (GMs) are used as a pore-forming agent, and coaxial electrospinning polylactic acid/gelatin fibers (PGFs) loaded with kartogenin (KGN) are used as a reinforcing agent and a drug delivery system to construct the nanofiber composite microchannel-containing injectable hydrogels (APA/CMCS/KGN@PGF/GM hydrogels). The in situ formation, micromorphology and porosity, swelling and degradation, mechanical properties, self-healing behavior, as well as drug release of the nanofiber composite microchannel-containing hydrogels are investigated. The hydrogel exhibits good self-healing ability, and the introduction of PGF nanofibers can significantly improve the mechanical properties. The drug delivery system can realize sustained release of KGN to match the process of cartilage repair. The microchannel structure effectively promotes bone marrow mesenchymal stem cell (BMSC) proliferation and ingrowth within the hydrogels. In vitro and animal experiments indicate that the APA/CMCS/KGN@PGF/GM hydrogels can enhance the chondrogenesis of BMSCs and promote neocartilage formation in the rabbit cartilage defect model.


Assuntos
Cartilagem Articular , Nanofibras , Animais , Coelhos , Hidrogéis/farmacologia , Hidrogéis/química , Gelatina/farmacologia , Materiais Biocompatíveis/farmacologia , Engenharia Tecidual
5.
ACS Biomater Sci Eng ; 9(5): 2625-2635, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37068303

RESUMO

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of -CHO/-NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the hydrogels were examined. The PLGA/PEG hydrogels cross-linked by dynamic Schiff base linkages exhibited good self-healing ability. Additionally, the PLGA/PEG hydrogels had good biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and could effectively support BMSC proliferation and deposition of glycosaminoglycans and upregulate the expression of cartilage-specific genes. In a rat cartilage defect model, PLGA/PEG hydrogels significantly promoted new cartilage formation. The results suggest the prospect of the PLGA/PEG hydrogels in cartilage tissue engineering.


Assuntos
Ácido Glutâmico , Engenharia Tecidual , Ratos , Animais , Engenharia Tecidual/métodos , Ácido Glutâmico/metabolismo , Bases de Schiff/metabolismo , Cartilagem/metabolismo , Materiais Biocompatíveis/farmacologia , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Polietilenoglicóis/farmacologia , Polietilenoglicóis/metabolismo
6.
Int J Biol Macromol ; 233: 123541, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36740115

RESUMO

The lack of interconnected macro-porous structure of most injectable hydrogels lead to poor cell and tissue infiltration. Herein, we present the fabrication of injectable macro-porous hydrogels based on "smashed gels recombination" strategy. Chitosan/polyethylene glycol-silicotungstic acid (CS/PEG-SiW) double-network hydrogels were prepared via dual dynamic interactions. The bulk CS/PEG-SiW hydrogels were then smashed into micro-hydrogels with average sizes ranging from 47.6 to 63.8 µm by mechanical fragmentation. The CS/PEG-SiW micro-hydrogels could be continuously injected and rapidly recombined into a stable porous hydrogel based on the dual dynamic interactions between micro-hydrogels. The average pore size of the recombined porous CS/PEG-SiW hydrogels ranged from 52 to 184 µm. The storage modulus, compress modulus and maximum compressive strain of the recombined porous CS/PEG-SiW1.0 hydrogels reached about 47.2 %, 28.2 % and 127.6 % of the values for their corresponding bulk hydrogels, respectively. The recombined porous hydrogels were cytocompatible and could effectively support proliferation and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In a rat cartilage defect model, recombined porous CS/PEG-SiW hydrogels could promote cartilage regeneration. Hematoxylin and eosin (H&E), Safranin-O/Fast green and immunohistochemical staining confirmed the accumulation of glycosaminoglycans (GAG) and type II collagen (Col II) in regenerated cartilage.


Assuntos
Quitosana , Ratos , Animais , Quitosana/química , Engenharia Tecidual , Hidrogéis/química , Polietilenoglicóis/farmacologia , Porosidade , Cartilagem , Materiais Biocompatíveis/farmacologia , Condrogênese , Recombinação Genética
7.
ACS Appl Mater Interfaces ; 13(28): 32673-32689, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34227792

RESUMO

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.


Assuntos
Materiais Biomiméticos/química , Regeneração Óssea/efeitos dos fármacos , Hidrogéis/química , Nanocompostos/química , Osteogênese/efeitos dos fármacos , Alicerces Teciduais/química , Adesivos/síntese química , Adesivos/química , Adesivos/toxicidade , Alendronato/análogos & derivados , Alendronato/toxicidade , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/toxicidade , Osso e Ossos/efeitos dos fármacos , Linhagem Celular , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Dextranos/síntese química , Dextranos/química , Dextranos/toxicidade , Durapatita/síntese química , Durapatita/química , Durapatita/toxicidade , Feminino , Hidrogéis/síntese química , Hidrogéis/toxicidade , Masculino , Camundongos , Nanocompostos/toxicidade , Ácido Poliglutâmico/síntese química , Ácido Poliglutâmico/química , Ácido Poliglutâmico/toxicidade , Ratos Sprague-Dawley , Suínos , Engenharia Tecidual/métodos
8.
ACS Appl Mater Interfaces ; 12(11): 12468-12477, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32091198

RESUMO

Bone tissue engineering scaffold based on microcarriers provides an effective approach for the repair of irregular bone defects. The implantation of microcarriers by injection can reduce surgical trauma and fill various irregular shaped bone defects. Microcarriers with porous structure and osteogenic properties have shown great potential in promoting the repair of bone defects. In this study, two kinds of hydroxyapatite/poly-(γ-benzyl-l-glutamate) (HA/PBLG) microcarriers were constructed by emulsion/in situ precipitation method and their structures and properties were studied. First, PBLG porous microcarriers were prepared by an emulsion method. Surface carboxylation of PBLG microcarriers was performed to promote the deposition of HA on PBLG microcarriers. Next, the modified porous PBLG microcarriers were used as the matrix, combined with the in situ precipitation method; the cluster HA and acicular HA were precipitated onto the surface of porous microcarriers in the presence of ammonia water and tri(hydroxymethyl)aminomethane (Tris) solution, respectively. The micromorphology, composition, and element distribution of the two kinds of microcarriers were characterized by TEM, SEM, and AFM. Adipose stem cells (ADSCs) were cultured on the cluster HA/PBLG and acicular HA/PBLG microcarriers, respectively. ADSCs could grow and proliferate normally on both kinds of microcarriers wherein the acicular HA/PBLG microcarriers were more favorable for early cell adhesion and showed a beneficial effect on mineralization and osteogenic differentiation of ADSCs. Successful healing of a rabbit femur defect verified the bone regeneration ability of acicular HA/PBLG microcarriers.


Assuntos
Portadores de Fármacos , Durapatita/química , Osteogênese/efeitos dos fármacos , Ácido Poliglutâmico/química , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Fêmur/citologia , Células-Tronco Mesenquimais/citologia , Porosidade , Coelhos
9.
ACS Biomater Sci Eng ; 6(3): 1715-1726, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33455400

RESUMO

Supramolecular hydrogels formed by noncovalent bonds are attractive "smart" materials, which can rapidly respond to external stimuli. However, only a handful of supramolecular hydrogels is applicable in tissue engineering, due to the instability and poor mechanical strength of noncovalent cross-linking hydrogels. Thus, a rigid and stable supramolecular hydrogel has been developed based on poly(l-glutamic acid) and 2-ureido-4[1H]pyrimidinones (UPy), and the UPy stacks are noncovalent cross-linking interactions. The hydrogels show excellent mechanical strength and stability, in sharp contrast to noncovalent hydrogels cross-linked by UPy dimers and covalent hydrogels cross-linked by esterification. The hydrogels also exhibit remoldability, self-healing, and thermoplastic printing characteristics, which are caused by the reversible supramolecular property of UPy stacks. Also, the formation of hydrogels dependent on UPy stacks is further investigated by atomic force microscope, small-angle X-ray scattering, in situ X-ray diffraction, circular dichroism, and UV-vis spectroscopies. Finally, the hydrogels show commendable biocompatibility and degradability, which have high potential applications in regenerative medicine.


Assuntos
Ácido Glutâmico , Hidrogéis , Polímeros , Pirimidinonas , Engenharia Tecidual
10.
ACS Appl Mater Interfaces ; 12(10): 11375-11387, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32068386

RESUMO

Adipose-derived stem cell (ASC) spheroids exhibit enhanced angiogenic efficacy toward ischemia treatment. Thus, it is necessary to develop an all-in-one platform that enables efficient spheroid production, collection, and injectable implantation in vivo. The present study fabricated a poly(l-glutamic acid) (PLGA)-based porous hydrogel that can not only produce ASC spheroids but also conveniently collect spheroids for in vivo implantation via minimally invasive injection to treat hind limb ischemia. PLGA was cross-linked with cystamine (Cys), which contains disulfide bonds, to form a porous hydrogel that could realize "gel-sol" transition by the reduction effect of glutathione (GSH). For one thing, it was found that the introduction of the disulfide bond in the PLGA hydrogel promoted cellular adhesion via combining fibronectin, preventing the formation of spheroids, while the introduction of polyethylene glycol monomethyl ether (mPEG) could disturb the effect of the disulfide bond on cellular adhesion, supporting spheroid formation inside the porous hydrogel. For another, the porous hydrogel transferred into a syringe could turn into liquid polymer solution within about 40 min for collection of the produced spheroids and in vivo injection. In addition, because of the lubrication of polymer solution, the spheroids were protected during the injection of the spheroids/polymer suspensoid through a 25G syringe needle, avoiding damages from shearing. After the in vivo injection, the enhanced paracrine secretion of ASC spheroids resulted in promoted angiogenesis and muscle regeneration, exhibiting obvious therapeutic effect on limb ischemia in mice after 21 days. At the same time, PLGA-based material exhibited well-performed biocompatibility in vivo.


Assuntos
Indutores da Angiogênese , Hidrogéis , Isquemia/metabolismo , Células-Tronco Mesenquimais , Esferoides Celulares , Adipatos , Tecido Adiposo/citologia , Indutores da Angiogênese/administração & dosagem , Indutores da Angiogênese/química , Indutores da Angiogênese/farmacologia , Animais , Células Cultivadas , Cistamina , Dissulfetos , Membro Posterior/irrigação sanguínea , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Transição de Fase , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo
11.
Biomater Sci ; 6(10): 2738-2749, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30175347

RESUMO

Shape memory scaffolds are minimally invasive cell carriers that are promising biomaterials for tissue regeneration. Since cell fate is critical for successful regeneration, the influence of mechanostructural stimuli induced by shape memory on cell fate is worthy of investigation. In this study, we developed a poly(l-glutamic acid)-based (PLGA-based) shape memory porous scaffold by cross-linking PLGA with poly(ε-caprolactone)-diols (PCL-diols) and by using the particle leaching method. After regulating the cross-linking density and molecular weight of the PCL-diols, the scaffolds exhibited excellent shape memory properties around physiological temperatures. The interconnected porous structure not only enabled the scaffold to be deformed to 20% of its original size but also supported tissue invasion. In vivo results demonstrated that the PLGA-based scaffold degraded within 6 months. Cell fate studies indicated that large dimensional deformation of the porous structure during the shape memory process induced significant death, detachment and reorganization of stem cells but had negligible effects on stemness and proliferation. These results indicate that the PLGA-based shape memory porous scaffold is a potential cell carrier for tissue regeneration, and they are also meaningful to investigate the effects of mechanostructural stimuli on stem cell fate in porous structures.


Assuntos
Ácido Láctico/química , Ácido Poliglutâmico/química , Ácido Poliglicólico/química , Células-Tronco/citologia , Alicerces Teciduais , Tecido Adiposo/citologia , Animais , Materiais Biocompatíveis/química , Proliferação de Células , Sobrevivência Celular , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Ratos Sprague-Dawley , Engenharia Tecidual
12.
Acta Biomater ; 51: 246-257, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28093366

RESUMO

Vascularization is of great importance to adipose tissue regeneration. Here we introduced a paradigm that using scaffold to induce ASC spheroids, so to promote vascularized adipose tissue regeneration. Poly (l-glutamic acid) (PLGA) was activated by EDC, followed by being cross-linked by Adipic dihydrazide (ADH) to form a homogeneous hydrogel. Lyophilization was then carried out to create porous structure. The PLGA hydrogel scaffold possessed a significant swollen hydrophilic network to weaken cell-scaffold adhesion but drive ASCs to aggregate to form spheroids. Increase of seeding cell density was proved to result in the increase of spheroid size, upregulating angiogenic genes (VEGF and FGF-2) expression by enhancing the hypoxia-induced paracrine secretion. Also, the adipogenic differentiation of ASCs was achieved in spheroids in vitro. Moreover, the in vivo vascularized adipose tissue regeneration was evaluated in the dorsum of nude mice. After 12weeks post-implantation, the significant angiogenesis was found in both adipogenic induced and non-induced engineered tissue. In adipogenic induced group, the clear ring-like morphology, the large vacuole in the middle of the cell and the Oil red O staining demonstrated adipose tissue formation. STATEMENT OF SIGNIFICANCE: Vascularization is of great importance to adipose tissue regeneration. Adipose derived stem cell (ASC) spheroids possessed not only the high efficiency of vascularization, but also the improved differentiation ability. Several research works have illustrated the advantage of ASC spheroids in vascularization. However, in adipose regeneration, ASC spheroid was rarely used. Even so, it is reasonable to believe that ASC spheroids hold a great promise in vascularized adipose tissue engineering. Thus in the present study, we introduced a method to create lots of ASC spheroids that acted as lots of individual adipogenesis and angiogenesis units inside of a porous hydrogel scaffold. Then, the scaffold carrying ASC spheroids was implanted subcutaneously in nude mice to preliminarily evaluate the adipose tissue generation and blood vessel formation.


Assuntos
Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Ácido Poliglutâmico/farmacologia , Esferoides Celulares/citologia , Células-Tronco/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Adipogenia/efeitos dos fármacos , Adulto , Indutores da Angiogênese/metabolismo , Tamanho Celular/efeitos dos fármacos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Ácido Láctico/síntese química , Ácido Láctico/química , Teste de Materiais , Ácido Poliglicólico/síntese química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Esferoides Celulares/ultraestrutura , Células-Tronco/efeitos dos fármacos , Células-Tronco/ultraestrutura
13.
Acta Biomater ; 10(1): 276-88, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24025620

RESUMO

In this study a novel kind of porous poly(l-glutamic acid) (PLGA)/chitosan polyelectrolyte complex (PEC) microsphere was developed through electrostatic interaction between PLGA and chitosan. By adjusting the formula parameters chitosan microspheres with an average pore size of 47.5 ± 5.4 µm were first developed at a concentration of 2 wt.% and freeze temperature of -20 °C. For self-assembly of the PEC microspheres porous chitosan microspheres were then incubated in PLGA solution at 37 °C. Due to electrostatic interaction a large amount of PLGA (110.3 µg mg(-1)) was homogeneously absorbed within the chitosan microspheres. The developed PEC microspheres retained their original size, pore diameters and interconnected porous structure. Fourier transform infrared spectroscopy, thermal gravimetric analysis and zeta potential analysis revealed that the PEC microspheres were successfully prepared through electrostatic interaction. Compared with microspheres fabricated from chitosan, the porous PEC microspheres were shown to efficiently promote chondrocyte attachment and proliferation. After injection subcutaneously for 8 weeks PEC microspheres loaded with chondrocytes were found to produce significant more cartilaginous matrix than chitosan microspheres. These results indicate that these novel fabricated porous PLGA/chitosan PEC microspheres could be used as injectable cell carriers for cartilage tissue engineering.


Assuntos
Cartilagem/fisiologia , Quitosana/farmacologia , Eletrólitos/farmacologia , Microesferas , Ácido Poliglutâmico/farmacologia , Regeneração/efeitos dos fármacos , Alicerces Teciduais/química , Animais , Cartilagem/efeitos dos fármacos , Fluorescência , Ácido Láctico/química , Camundongos , Microscopia Eletrônica de Varredura , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Eletricidade Estática
14.
Colloids Surf B Biointerfaces ; 113: 302-11, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24121073

RESUMO

The magnetic polymer microcapsules, as a promising environmental stimuli-responsive delivery vehicle, have been increasingly exploited to tackle the problem of remotely navigated delivery. This study presented a novel design and fabrication of magnetic poly(L-glutamic acid)/chitosan (PGA/CS) microcapsules. Magnetic Fe3O4 nanoparticles were in situ synthesized inside nanoporous PGA/CS microcapsules and resultant magnetic PGA/CS microcapsules were characterized. Mitoxantrone (MTX), an antineoplastic drug, was chosen as a water-soluble model drug to research the loading and release properties of the microcapsules. The results showed the carboxylate groups of PGA within polyelectrolyte walls could be used as binding sites for the absorption of iron ions and reaction sites for the synthesis of magnetic nanoparticles. Magnetic PGA/CS microcapsules were dissected using a dual-beam scanning electron microscope/focused ion beam (SEM/FIB) for morphological and microstructural examination. It was found that Fe3O4 nanoparticles with size of about 10nm were homogeneously dispersed in the polymer matrix and adhered to the pore walls of the microcapsules. Increasing the concentration of iron ions led to an increasing loading content of Fe3O4 nanoparticles and an increase in the resultant magnetization. The magnetic PGA/CS microcapsules could be easily manipulated by an external magnetic field. The MTX loading capacity depended on loading time and MTX concentration. The high loading could be ascribed to spontaneous deposition of MTX induced by electrostatic interaction. The microcapsules exhibited sustained release behavior. The MTX release from microcapsules could be best described using Korsmeyer-Peppas and Baker-Lonsdale models, indicating the diffusion mechanism of drug release from both PGA/CS microcapsules and magnetic PGA/CS microcapsules. Therefore, the novel magnetic PGA/CS microcapsules are expected to find application in drug delivery systems because of the properties of magnetic sensitivity, high drug loading and sustained release.


Assuntos
Quitosana/química , Ácido Glutâmico/química , Nanopartículas de Magnetita/química , Ácido Poliglutâmico/química , Polímeros/química , Sistemas de Liberação de Medicamentos/métodos
15.
Colloids Surf B Biointerfaces ; 86(1): 218-24, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21536416

RESUMO

Bioactive PLLA/surface-grafted silica (g-SiO2) nanocomposite scaffolds were fabricated by solid-liquid phase separation method. And solid PLLA/g-SiO2 nanocomposite films were prepared by solution casting method. A series of parallel tube-like morphology and internal ladder-like structure of PLLA/g-SiO2 nanocomposite scaffolds were observed by SEM. The formation of bone-like apatite in the simulated body fluid (SBF) was characterized by XRD, IR, SEM, EDS and weight measurement. The silica incorporation favors the formation of apatite. The growth of apatite with immersion time is found on the surfaces of both the PLLA/g-SiO2 nanocomposite scaffolds and the films. The potential mechanism is that silanol groups of g-SiO2 in the nanocomposites serve as nucleation sites for the formation of bone-like apatite crystals.


Assuntos
Apatitas/química , Líquidos Corporais/química , Ácido Láctico/química , Nanocompostos/química , Polímeros/química , Dióxido de Silício/química , Modelos Teóricos , Poliésteres
16.
Macromol Biosci ; 11(7): 970-7, 2011 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21520504

RESUMO

A novel PAA-b-PLGA diblock copolymer is synthesized and characterized that has excellent cell adhesion and biocompatibility. Fluorescent DiO labeling is used to monitor the attachment and growth of hASCs on the film surface, and cell proliferation over time is studied. Results show that PLLA modified by a CS/PAA-b-PLGA multilayer film can promote the attachment of human hASCs and provide an advantageous environment for their proliferation. The multilayer film presents excellent biocompatibility and cell adhesive properties, which will provide a new choice for improving the cell attachment in surface modification for tissue engineering. Hydroxyl, carboxyl and amine groups in the CS/PAA-b-PLGA multilayer film may be combined with drugs and growth factors for therapy and differentiation.


Assuntos
Resinas Acrílicas/síntese química , Ácido Glutâmico/síntese química , Resinas Acrílicas/química , Materiais Biocompatíveis/química , Adesão Celular , Proliferação de Células , Células Cultivadas , Portadores de Fármacos , Ácido Glutâmico/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células-Tronco/metabolismo , Propriedades de Superfície , Alicerces Teciduais
17.
Macromol Biosci ; 11(9): 1211-7, 2011 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-21674805

RESUMO

A methoxypoly(ethylene glycol)-block-poly(α,L-glutamic acid) (mPEGGA) diblock copolymer is synthesized. Using QCM measurements, it is shown that (CS/mPEGGA)(n) film construction takes place over two build-up stages (exponential-to-linear). UV-vis spectra reveal the regular increase of the multilayer film growth at different molecular weights of mPEGGA. Contact angle and surface morphology investigation prove that the hydrophilicity of CS/mPEGGA multilayer film-modified substrate becomes better and the surface becomes rough. Significantly reduced cell adhesion is observed on the CS/mPEGGA multilayer film coated surface.


Assuntos
Adesão Celular , Quitosana/química , Materiais Revestidos Biocompatíveis/síntese química , Ácido Glutâmico/química , Polietilenoglicóis/química , Polímeros/síntese química , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Teste de Materiais , Peso Molecular , Polímeros/química , Células-Tronco/citologia , Propriedades de Superfície
18.
Macromol Biosci ; 9(3): 268-78, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-18855946

RESUMO

A new biocompatible film based on chitosan and poly(L-glutamic acid) (CS/PGA), created by alternate deposition of CS and PGA, was investigated. FT-IR spectroscopy, UV-vis spectroscopy and QCM were used to analyze the build-up process. The growth of CS and PGA deposition are both exponential to the deposition steps at first. After about 9 (CS/PGA) depositions, the exponential to linear transition takes place. QCM measurements combined with UV-vis spectra revealed the increase in the multilayer film growth at different pH (4.4, 5.0 and 5.5). The build-up of the multilayer stops after a few depositions at pH = 6.5. A muscle myoblast cell (C2C12) assay showed that (CS/PGA)(n) multilayer films obviously promote C2C12 attachment and growth.


Assuntos
Quitosana/química , Materiais Revestidos Biocompatíveis/química , Mioblastos/citologia , Ácido Poliglutâmico/química , Animais , Materiais Biocompatíveis/química , Adesão Celular , Linhagem Celular , Proliferação de Células , Concentração de Íons de Hidrogênio , Teste de Materiais , Camundongos , Análise Espectral , Propriedades de Superfície
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