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1.
Science ; 375(6576): eaaw9021, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34990240

RESUMO

Epithelial organoids are stem cell­derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.


Assuntos
Mucosa Intestinal/crescimento & desenvolvimento , Organogênese , Organoides/crescimento & desenvolvimento , Engenharia Tecidual , Animais , Diferenciação Celular , Forma Celular , Células Epiteliais/citologia , Hidrogéis , Mucosa Intestinal/anatomia & histologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Organoides/anatomia & histologia , Organoides/citologia , Organoides/metabolismo , Celulas de Paneth/citologia , Receptores Notch/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/fisiologia , Técnicas de Cultura de Tecidos , /metabolismo
2.
J Mater Chem B ; 4(6): 1035-1039, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27127630

RESUMO

We present a versatile and facile method to enhance user-control of small molecule drug release from a poly(ethylene glycol)-based hydrogel using the host/guest complex formed between an azobenzene derivative guest and a ß-cyclodextrin host. A model drug is formed from a short peptide containing a fluorophore and an azobenzene functional group on one terminus. Upon irradiation with UV light, azobenzene isomerization leads to decreased complex formation and an on-demand acceleratation of the release rate of an entrapped model drug.

3.
Sci Rep ; 5: 17814, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26638791

RESUMO

Here, we demonstrate the flexibility of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels for modeling tumor progression. The PEG hydrogels were formed using thiol-ene chemistry to incorporate a matrix metalloproteinase-degradable peptide crosslinker (KKCGGPQG↓IWGQGCKK) permissive to proteolytic remodeling and the adhesive CRGDS peptide ligand. Tumor cell function was investigated by culturing WM239A melanoma cells on PEG hydrogel surfaces or encapsulating cells within the hydrogels, and either as monocultures or indirect (non-contact) cocultures with primary human dermal fibroblasts (hDFs). WM239A cluster size and proliferation rate depended on the shear elastic modulus for cells cultured on PEG hydrogels, while growth was inhibited by coculture with hDFs regardless of hydrogel stiffness. Cluster size was also suppressed by hDFs for WM239A cells encapsulated in PEG hydrogels, which is consistent with cells seeded on top of hydrogels. Notably, encapsulated WM239A clusters and single cells adopted invasive phenotypes in the hDF coculture model, which included single cell and collective migration modes that resembled invasion from human melanoma patient-derived xenograft tumors encapsulated in equivalent PEG hydrogels. Our combined results demonstrate that peptide-functionalized PEG hydrogels provide a useful platform for investigating aspects of tumor progression in 2D and 3D microenvironments, including single cell migration, cluster growth and invasion.


Assuntos
Progressão da Doença , Modelos Biológicos , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Hidrogéis , Camundongos Nus , Polietilenoglicóis/química , Células Estromais/metabolismo
4.
Soft Matter ; 10(46): 9230-6, 2014 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-25265090

RESUMO

Studies focused on understanding the role of matrix biophysical signals on cells, especially those when cells are encapsulated in hydrogels that are locally remodelled, are often complicated by appropriate methods to measure differences between the bulk and local material properties. From this perspective, stress-relaxing materials that allow long-term culture of embedded cells provide an opportunity to elucidate aspects of this biophysical signalling. In particular, rheological characterization of the stress relaxation properties allows one to link a bulk material measurement to local aspects of cellular functions by quantifying the corresponding cellular forces that must be applied locally. Here, embryonic stem cell-derived motor neurons were encapsulated in a well-characterized covalently adaptable bis-aliphatic hydrazone crosslinked PEG hydrogel, and neurite outgrowth was observed over time. Using fundamental physical relationships describing classical mechanics and viscoelastic materials, we calculated the forces and energies involved in neurite extension, the results of which provide insight to the role of biophysical cues on this process.


Assuntos
Hidrazonas/química , Hidrogéis/química , Aldeídos/química , Axônios/metabolismo , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Hidrogéis/farmacologia , Peptídeos/química , Polietilenoglicóis/química , Reologia , Estresse Mecânico
5.
J Biomater Sci Polym Ed ; 23(12): 1613-28, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21888758

RESUMO

Due to the high importance of bacterial infections in medical devices there is an increasing interest in the design of anti-fouling coatings. The application of substrates with controlled chemical gradients to prevent microbial adhesion is presented. We describe here the co-polymerization of poly(ethylene glycol) dimethacrylate with a hyperbranched multimethacrylate (H30MA) using a chemical gradient generator; and the resulting films were characterized with respect to their ability to serve as coating for biomedical devices. The photo-polymerized materials present special surface properties due to the hyperbranched structure of H30MA and phase separation at specific concentrations in the PEGDM matrix. This approach affords the investigation of cell response to a large range of different chemistries on a single sample. Two bacterial strains commonly associated with surgical site infections, Escherichia coli and Pseudomonas aeruginosa, have been cultured on these substrates to study their attachment behaviour. These gradient-coated samples demonstrate less bacterial adhesion at higher concentrations of H30MA, and the adhesion is substantially affected by the extent of surface phase segregation.


Assuntos
Aderência Bacteriana/fisiologia , Incrustação Biológica/prevenção & controle , Metacrilatos/química , Polietilenoglicóis/química , Escherichia coli/fisiologia , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Estrutura Molecular , Polimerização , Pseudomonas aeruginosa/fisiologia , Propriedades de Superfície
6.
J Biomed Mater Res A ; 96(1): 196-203, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21105168

RESUMO

High-throughput methods allow rapid examination of parameter space to characterize materials and develop new polymeric formulations for biomaterials applications. One limitation is the difficulty of preparing libraries and performing high-throughput screening with conventional instrumentation and sample preparation. Here, we describe the fabrication of substrate materials with controlled gradients in composition by a rapid method of micromixing followed by a photopolymerization reaction. Specifically, poly(ethylene glycol) dimethacrylate was copolymerized with a hyperbranched multimethacrylate (P1000MA or H30MA) in a gradient manner. The extent of methacrylate conversion and the final network composition were determined by near-infrared spectroscopy, and mechanical properties were measured by nanoindentation. A relationship was observed between the elastic modulus and network crosslinking density. Roughness and hydrophilicity were increased on surfaces with a higher concentration of P1000MA. These results likely relate to a phase segregation process of the hyperbranched macromer that occurs during the photopolymerization reaction. On the other hand, the decrease in the final conversion in H30MA polymerization reactions was attributed to the lower termination rate as a consequence of the softening of the network. Valvular interstitial cell attachment was evaluated on these gradient substrates as a demonstration of studying cell morphology as a function of the local substrate properties. Data revealed that the presence of P1000MA affects cell-material interaction with a higher number of adhered cells and more cell spreading on gradient regions with a higher content of the multifunctional crosslinker.


Assuntos
Comunicação Celular , Microfluídica/métodos , Polietilenoglicóis/química , Polímeros/química , Animais , Materiais Biocompatíveis/química , Células Cultivadas , Células Endoteliais/citologia , Ensaios de Triagem em Larga Escala/métodos , Teste de Materiais , Metacrilatos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Suínos
7.
J Dent Res ; 88(8): 681-92, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19734453

RESUMO

Craniofacial injuries require a variety of different cell types to repopulate areas of bone, cartilage, tendon, and fat. Mesenchymal stem cells (MSCs) provide a multipotent cell source for tissue engineering of this area, particularly when the cells are delivered via a 3D hydrogel environment. MSC differentiation into cartilage, bone, and fat has been investigated through a variety of techniques, some of which include the use of synthetic hydrogel scaffolds, integration of extracellular matrix components and other natural gel chemistries, microparticle delivery of growth factors, simultaneous mechanical stimulation, and the delivery of microRNA. This review aims to summarize the most recent studies involving the synthesis and application of 3D hydrogels to induce the differentiation of encapsulated MSCs and their subsequent matrix production.


Assuntos
Hidrogéis/síntese química , Transplante de Células-Tronco Mesenquimais/métodos , Regeneração/fisiologia , Tecidos Suporte , Implantes Absorvíveis , Fenômenos Biomecânicos , Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Humanos , Hidrogéis/química , Células-Tronco Mesenquimais/fisiologia , Propriedades de Superfície , Engenharia Tecidual/métodos , Tecidos Suporte/química
8.
J Tissue Eng Regen Med ; 2(7): 418-29, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18727135

RESUMO

Chondrocytes were encapsulated in non-degrading and partially degrading poly(ethylene glycol) (PEG) gels in apposition to native cartilage layers in order to examine the effects of gel degradation on the integration of regenerated cartilaginous matrix with native tissue. In addition, the effect of collagenase predigestion of the native cartilage surfaces on this integration was examined in studies with partially degrading co-polymer gels. Integration was quantitatively assessed by mechanical measurements of adhesive strength, and visualized by histological staining and non-destructive ultrasound analysis. Constructs with encapsulated chondrocytes and a non-degrading gel layer had significantly higher adhesive strength than partially degrading gel constructs and non-degrading gel constructs without cells. In addition, better maintenance of proper cell morphology was observed near the gel-cartilage interface in non-degrading gel constructs than in partially degrading gel constructs after 8 weeks of in vitro culture. Facile collagen distribution in the degrading gels appeared to have a significant effect on mechanical adhesion measurements only when the native cartilage surface was predigested with collagenase. Ultrasound analysis provided qualitative evidence of cartilaginous matrix evolution and non-destructive imaging of developing constructs and the interface between newly formed matrix and existing cartilage tissue.


Assuntos
Cartilagem/metabolismo , Condrócitos/metabolismo , Colagenases/metabolismo , Géis/química , Hidrogéis/química , Materiais Biocompatíveis/química , Cartilagem/química , Adesão Celular , Desenho de Equipamento , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Modelos Biológicos , Peso Molecular , Polietilenoglicóis/química , Estresse Mecânico , Engenharia Tecidual/métodos , Ultrassom
9.
J Biomed Mater Res ; 57(2): 217-23, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11484184

RESUMO

Hydrogels have been used in biology and medicine for many years, and they possess many properties that make them advantageous for tissue engineering applications. Their high water content and tissue-like elasticity are similar to the native extracellular matrix of many tissues. In this work, we investigated the potential of a modified poly(vinyl alcohol) (PVA) hydrogel as a biomaterial for tissue engineering applications. First, the ability of NIH3T3 fibroblast cells to attach to PVA hydrogels was evaluated. Because of PVA's extremely hydrophilic nature, important cell adhesion proteins do not adsorb to PVA hydrogels, and consequently, cells are unable to adhere to the hydrogel. By covalently attaching the important cell adhesion protein fibronectin onto the PVA hydrogel surface, the rate of fibroblast attachment and proliferation was dramatically improved, and promoted two-dimensional cell migration. These studies illustrate that a fibronectin-modified PVA hydrogel is a potential biomaterial for tissue engineering applications.


Assuntos
Adesão Celular/fisiologia , Divisão Celular/fisiologia , Movimento Celular/fisiologia , Fibronectinas/metabolismo , Hidrogéis/química , Álcool de Polivinil/química , Células 3T3 , Animais , Proteínas Sanguíneas/metabolismo , Hidrogéis/síntese química , Camundongos , Estrutura Molecular , Engenharia Tecidual/métodos
10.
Cells Tissues Organs ; 169(3): 272-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11455123

RESUMO

Chronic foreign body reactions have limited the successful application of alloplastic implants for treatment of temporomandibular joint (TMJ) disorders. There is a great clinical need for new materials with enhanced properties for application in the diarthrodial joint. Photopolymerizations may provide many advantages for fabricating new biomaterials for the TMJ and may address some of the notable differences between the TMJ and other articulations. Specifically, the feasibility of trans-tissue (i.e. through the skin) photopolymerizations may yield less-invasive surgical procedures. Also, novel 3-dimensional photoprocessing techniques may be used to fabricate patient-specific alloplastic devices for improved compliance and efficacy. Finally, the mild conditions necessary for photopolymerizations make the reaction ideal for encapsulating cells with the potential to create constructs for tissue engineering, which may be beneficial for disk replacement therapies.


Assuntos
Materiais Biocompatíveis/síntese química , Articulação Temporomandibular/cirurgia , Animais , Materiais Biocompatíveis/química , Engenharia Biomédica , Colágeno/síntese química , Colágeno/química , Reagentes para Ligações Cruzadas , Humanos , Técnicas In Vitro , Teste de Materiais , Osteoblastos/citologia , Fotoquímica , Próteses e Implantes , Ratos , Transtornos da Articulação Temporomandibular/cirurgia
11.
Biomaterials ; 22(13): 1779-86, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11396881

RESUMO

Polymerization of a tetrafunctional monomer was investigated under a variety of photoinitiation conditions to assess the ability to form thick materials in situ for orthopaedic applications. The major biological concerns include local cell and tissue necrosis due to the polymerization exotherm and low conversions at greater depths due to light attenuation through thick samples. Experimental results indicate that depth of cure and temperature rises are controllable by altering the photoinitiator concentration, initiating light intensity, and type of photoinitiator. For example, no measurable conversion was detected at a 1.0 cm depth when polymerization was initiated with 1.0 wt% DMPA and 100 mW/cm2 ultraviolet light, whereas approximately 40% conversion was obtained when the initiator concentration was lowered to 0.1 wt%. This conversion was further increased to approximately 55% when a photobleaching initiator system was employed. At the highest rate of initiation studied (i.e., 1.0 wt% DMPA irradiated with 100 mW/cm2 ultraviolet light), a maximum temperature of approximately 49 degrees C was reached at the sample surface; however, this temperature dramatically decreased to approximately 33 degrees C when the light intensity was decreased to 25 mW/cm2. Finally, dual initiating systems that synergistically combine the advantages of photoinitiation and thermal initiation were investigated.


Assuntos
Materiais Biocompatíveis/química , Polímeros/química , Fotoquímica , Espectrofotometria Ultravioleta , Temperatura
12.
Biomaterials ; 22(6): 619-26, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11219727

RESUMO

The thickness of human articular cartilage has been reported to vary from less than 0.5 up to 7 mm. Hence, tissue engineered cartilage scaffolds should be able to span the thickness of native cartilage to fill defects of all shapes and sizes. In this study, we demonstrate the potential for using photopolymerization technology to encapsulate chondrocytes in poly(ethylene oxide) hydrogels, which vary in thickness from 2 to 8 mm. Chondrocytes, encapsulated in an 8 mm thick, photocrosslinked hydrogel and cultured in vitro for 6 weeks, remained viable and produced cartilaginous tissue throughout the construct comparable to a 2 mm thick gel as seen both histologically and biochemically. In addition, the total collagen and glycosaminoglycan contents per wet weight of the 8 mm thick cell-polymer construct were 0.13 +/- 0.01 and 0.25 +/- 0.03%, respectively, and did not vary significantly as a function of spatial position in the construct. The histological evidence and the biochemical content were similar in all constructs of varying thickness. The results suggest that photocrosslinked hydrogels are promising scaffolds for tissue engineering cartilage as cell viability is readily maintained; uniform cell seeding is easy to achieve: and the biochemical content of the extracellular matrix is not compromised as the scaffold thickness is increased from 2 to 8 mm.


Assuntos
Cartilagem , Hidrogéis , Polietilenoglicóis , Animais , Bovinos , Humanos , Hidrogéis/química , Fotoquímica , Polietilenoglicóis/química
13.
J Biomater Sci Polym Ed ; 12(11): 1253-65, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11853390

RESUMO

The ability of osteoblasts to attach and function normally on scaffolds fabricated from synthetic materials is essential for musculoskeletal tissue engineering applications. In this study, the osteoconductivity of polymer networks formed from multifunctional lactic acid oligomers was assessed. These oligomers form highly crosslinked networks via a photoinitiated polymerization, which provides potential advantages for many orthopaedic applications. Depending on the initial oligomer chemistry and the resultant polymer hydrophobicity, protein adsorption and osteoblast function varied significantly between the various lactic acid based polymer chemistries. Results were compared to control polymers of tissue culture polystyrene (TCPS) and 50:50 poly(lactic-co-glycolic acid) (PLGA). The viability of osteoblasts attached to poly(2EG10LA) and poly(2EG6LA) was close to the TCPS and PLGA after 7 and 14 days of culture, whereas cell viability was approximately 50% lower on poly(8EG6LA). Additionally, the alkaline phosphatase activity and mineralization of attached osteoblasts were similar on poly(2EG10LA) and PLGA, whereas these markers of bone formation were significantly lower for poly(2EG6LA) and poly(8EG6LA). For example, the alkaline phosphatase activity of rat calvarial osteoblasts attached to poly(2EG10LA) was 0.048 +/- 0.006 micromol mg(-1) protein-min, but only 0.030 +/- 0.003 micromol mg(-1) protein-min for osteoblasts attached to poly(8EG6LA) after 14 days of culture. Finally, osteoblasts were seeded onto three-dimensional scaffolds to demonstrate the applicability of the scaffolds for bone tissue engineering.


Assuntos
Materiais Biocompatíveis/química , Ácido Láctico/química , Osteoblastos/citologia , Adsorção , Fosfatase Alcalina/metabolismo , Animais , Animais Recém-Nascidos , Adesão Celular , Células Cultivadas , Clorobenzenos/química , Reagentes para Ligações Cruzadas/farmacologia , Ácido Láctico/metabolismo , Modelos Químicos , Músculos/metabolismo , Osteoblastos/metabolismo , Osteoblastos/ultraestrutura , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Poliestirenos/química , Ratos , Succinimidas/química , Fatores de Tempo
14.
Biomaterials ; 21(23): 2395-404, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11055287

RESUMO

Many orthopaedic injuries could benefit from a high-strength and degradable material with good tissue compatibility. In addition, there is a great clinical need for materials which are easily contoured or placed into complex-shaped defects by a surgeon. We have rationally designed a new class of photocrosslinkable polyanhydride monomers which in situ form high-strength and surface eroding networks of complex geometries. This paper highlights the advantages of these materials for orthopaedic applications and the technique of photopolymerization for reacting these monomers under physiological conditions. The rationale for the material design, photopolymerization kinetics, degradation behavior, and histology in subcutaneous tissue and a model bone defect are presented.


Assuntos
Anidridos/química , Materiais Biocompatíveis , Animais , Biodegradação Ambiental , Cinética , Masculino , Fotoquímica , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
15.
J Biomater Sci Polym Ed ; 11(5): 439-57, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10896041

RESUMO

This work investigates the cytocompatibility of several photoinitiating systems for potential cell encapsulation applications. Both UV and visible light initiating schemes were examined. The UV photoinitiators included 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure 184), 2-methyl-1-[4-(methylthio) phenyl]-2-(4-morpholinyl)-1-propanone (Irgacure 907), and 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Darocur 2959). The visible light initiating systems included camphorquinone (CQ) with ethyl 4-N,N-dimethylaminobenzoate (4EDMAB) and triethanolamine (TEA) and the photosensitizer isopropyl thioxanthone. A cultured fibroblast cell line, NIH/3T3, was exposed to the photoinitiators at varying concentrations from 0.01% (w/w) to 0.1% (w/w) with and without the presence of initiating light. The results demonstrated that at low photoinitiator concentrations (< or = 0.01% (w/w)), all of the initiator molecules were cytocompatible with the exception of CQ, Irgacure 651, and 4EDMAB which had a relative survival approximately 50% lower than a control. In the presence of low intensity initiating light (approximately 6 mWcm(-2) of 365 nm UV light and approximately 60 mWcm(-2) of 470-490 nm visible light) and initiating radicals, Darocur 2959 at concentrations < or = 0.05% (w/w) and CQ at concentrations < or = 0.01% (w/w) were the most promising cytocompatible UV and visible light initiating systems, respectively. To demonstrate the potential use of cytocompatible photoinitiating systems in cell encapsulation applications, chondrocytes were encapsulated in a photocrosslinked hydrogel using 0.05% (w/w) Darocur 2959 (cytocompatible) and 0.01% (w/w) Irgacure 651 (cyto-incompatible). After photopolymerizing for 10 minutes with approximately 8 mWcm(-2) of 365 nm light, nearly all the chondrocytes survived the process with Darocur 2959 while very few of the chondrocytes survived the process with Irgacure 651.


Assuntos
Células 3T3/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Luz , Fármacos Fotossensibilizantes/farmacologia , Raios Ultravioleta , Células 3T3/efeitos da radiação , Animais , Bovinos , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Condrócitos/efeitos da radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Camundongos
16.
J Biomed Mater Res ; 51(3): 352-9, 2000 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-10880076

RESUMO

A unique class of surface-eroding polyanhydrides was developed and explored for use in medical applications requiring high-strength biomaterials (e.g., orthopedics). In particular, dimethacrylated anhydride monomers were synthesized that photopolymerize quickly to render densely crosslinked polymer networks that degrade from the surface only by hydrolysis of labile anhydride linkages. Previous research on these materials has shown that the rate of hydrolysis of the degradable linkages is dependent on the hydrophobicity of the network composition. This article demonstrates the versatility in controlling the degradation process and resulting cellular response in these materials through the incorporation of new chemistries and the formation of polymer-polymer composite structures. Specifically, the rate of mass loss was controlled by the addition of hydrophobic linear polymers [e.g., poly(methyl methacrylate)] or monovinyl monomers based on hydrophobic natural components (e.g., cholesterol, steric acid). In addition, a newly established photografting method was used to modify the network surface chemistry with cholesterol- and stearic acid-based polymer grafts to control the degradation front and cellular interactions at the polymer-tissue interface. Finally, a porogen leaching method was used to form porous polyanhydride constructs, which can be subsequently filled with osteoblasts photoencapsulated in a hydrogel, as potential synthetic allograft materials for tissue engineering bone.


Assuntos
Anidridos/química , Anidridos/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Polímeros/química , Polímeros/síntese química , Biodegradação Ambiental , Fenômenos Biomecânicos , Engenharia Biomédica , Osso e Ossos/cirurgia , Reagentes para Ligações Cruzadas , Humanos , Técnicas In Vitro , Teste de Materiais , Microscopia Eletrônica de Varredura , Fotoquímica , Propriedades de Superfície
17.
Biomaterials ; 21(11): 1181-8, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10817271

RESUMO

Novel, high modulus, degradable polymers were prepared from methacrylated anhydride monomers of tricarballylic acid (MTCA) and pyromellitylimidoalanine (MPMA-ala). Kinetic studies indicate that the time scale of photopolymerization of MTCA (< 30 s) is suitable for in vivo applications. Additionally, the tensile modulus of copolymers of these novel monomers with methacrylic anhydride (MA) ranged from 0.8 to 2.1 GPa, which lies between the modulus of trabecular and cortical bone. Degradation studies indicate that the copolymers of MTCA and MPMA-ala with MA are initially surface degrading, which is important to maintaining polymer strength through the degradation process. Monomers such as these that can be rapidly polymerized using ultraviolet or blue light into high modulus degradable materials have great potential in orthopedics.


Assuntos
Anidridos , Materiais Biocompatíveis , Ortopedia , Polímeros , Ácidos Tricarboxílicos , Varredura Diferencial de Calorimetria , Fotoquímica , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Tricarboxílicos/química
18.
J Pharm Sci ; 89(1): 45-51, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10664537

RESUMO

This paper describes a novel approach to obtain desired release profiles from diffusion-controlled matrix devices by employing nonuniform initial concentration profiles theoretically and experimentally. Theoretically, a model was developed to examine the effect of nonuniform initial concentration profiles on matrix release behavior, and an optimization technique was investigated to determine suitable nonuniform initial concentration profiles which provide desired release patterns. Experimentally, release rates of an organic dye from photopolymerized matrix devices were measured to test the application of these mathematical techniques and the efficacy of photolaminated matrices in approximating the optimized release behavior. All system parameters were measured by independent experiments, and the experimental release data agree very well with the computed results.


Assuntos
Sistemas de Liberação de Medicamentos , Metacrilatos/química , Modelos Químicos , Acrilatos/química , Reagentes para Ligações Cruzadas/química , Preparações de Ação Retardada , Difusão , Etilenoglicóis/química , Hidrogéis/química , Computação Matemática , Fotoquímica
19.
J Biomed Mater Res ; 46(2): 271-8, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10380006

RESUMO

High-strength, surface-eroding polymers were synthesized from methacrylated anhydride monomers of sebacic acid (MSA) and 1,6-bis(carboxyphenoxy) hexane (MCPH). These multifunctional monomers were photopolymerized using ultraviolet light to produce highly crosslinked polyanhydride networks. Through this approach, the crosslinking density of the resulting polymer network was used to control the final mechanical properties, while the degradation time scale was controlled by the chemical composition of the network. The combined hydrophobicity of the polymer backbone with the hydrolytically labile anhydride linkages led to surface-eroding networks, as confirmed by linear cumulative mass loss profiles as a function of degradation time for crosslinked polymer disks. By copolymerizing varying amounts of MSA and MCPH, the degradation rate of the final network was controlled from 2 days to 1 year. The tensile modulus of crosslinked poly(MSA) (1.4 GPa) was nearly an order of magnitude larger than that of linear poly(sebacic acid). In general, the mechanical properties of the crosslinked polyanhydrides networks were within ranges of those reported for cortical and trabecular bone. However, unlike bulk degrading polyesters such as poly(lactic acid), these surface eroding networks maintained >70% of their tensile modulus with 50% mass degradation.


Assuntos
Resinas Acrílicas/química , Anidridos/química , Substitutos Ósseos , Ácidos Dicarboxílicos , Hexanos/química , Resinas Acrílicas/síntese química , Reagentes para Ligações Cruzadas , Ácidos Decanoicos/química , Hidrólise , Cinética , Ortopedia , Polímeros/síntese química , Resistência à Tração , Raios Ultravioleta
20.
Nat Biotechnol ; 17(2): 156-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10052351

RESUMO

We have developed a new family of photopolymerizable, methacrylated anhydride monomers and oligomers that combine high strength, controlled degradation, and photoprocessibility in a singular system. Networks with degradation times ranging from 1 week to nearly 1 year and that retain up to 90% of their tensile modulus at 40% mass loss are attainable. In vivo studies in rats have shown that these networks possess excellent osteocompatibility. These combined properties could offer many advantages in medical applications ranging from dentistry to orthopedics.


Assuntos
Anidridos/química , Materiais Biocompatíveis , Osso e Ossos , Polímeros , Animais , Hidrólise , Fotoquímica , Ratos , Ratos Sprague-Dawley , Espectrofotometria Infravermelho/métodos
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