RESUMO
Medical polyurethanes have emerged as a leading choice for biomedical applications owing to their exceptional biocompatibility and good physical and mechanical properties. Catalysts play a crucial role as additives in the synthesis of medical polyurethanes, enhancing synthesis efficiency and material properties. However, the catalysts used may affect the biocompatibility of polyurethanes and pose potential harm to human health. This review encapsulates the latest findings regarding the catalysts employed in the synthesis of medical polyurethane materials and their biotoxicity. Initially, we reviewed the prevalent types of catalysts used in the synthesis of medical polyurethane materials and described their distinctive characteristics. Subsequently, our focus shifted to exploring the potential biotoxicity associated with these catalysts. Finally, we provided a forward-looking perspective and recommendations for the future trajectory of catalyst selection in the synthesis of medical polyurethane materials. By acquiring a more profound understanding of the properties and biotoxicity of catalysts used in the synthesis of medical polyurethane materials, and by uncovering existing issues and challenges, we can better guide the design of medical polyurethane materials. This, in turn, enables us to chart the course for future development and ultimately enhance the biocompatibility and safety profiles of medical polyurethane materials. Such advancements will promote the continued development and application of medical polyurethane materials in clinical settings.
Assuntos
Materiais Biocompatíveis , Poliuretanos , Poliuretanos/síntese química , Poliuretanos/química , Poliuretanos/toxicidade , Catálise , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , HumanosRESUMO
Metal ions play critical roles in facilitating peptide folding and inducing conformational transitions, thereby impacting on the biological activity of many proteins. However, the effect of metal sites on the hierarchical structures of biopolymers is still poorly understood. Herein, inspired by metalloproteins, we report an order-to-order conformational regulation in synthetic polymers mediated by a variety of metal ions. The copolymers are decorated with clinically available desferrioxamine (DFO) as an exogenous ligand template, which presents a geometric constraint toward peptide backbone via short-range hydrogen bonding interactions, thus dramatically altering the secondary conformations and self-assembly behaviors of polypeptides and allowing for a controllable ß-sheet to α-helix transition modulated by metal-ligand interactions. These metallopolymers could form ferritin-inspired hierarchical structures with high stability and membrane activity for efficient brain delivery across the blood-brain barrier (BBB) and long-lasting magnetic resonance imaging (MRI) in vivo.
Assuntos
Polímeros , Proteínas , Polímeros/química , Ligantes , Peptídeos/química , Metais/química , ÍonsRESUMO
Biodegradable shape memory polymers are promising biomaterials for stents used in minimally invasive surgical procedures such as intestinal stents. Herein, a series of biodegradable shape memory polyurethanes (SMPUs) containing a novel phenylalanine-derived chain extender (PHP) are synthesized. Inspired by the fact that the function of biomacromolecules such as proteins is rich and varied because of the multiple combinations of the amino acid in highly evolved biosystems, this study finds that the sequence distribution of PHP in SMPU will also have a great influence on the phase structure and degradation behavior, especially the difference of surface morphology caused by degradation. Considering that the transition temperature (Ttrans ) of SMPU obtained is higher than physiological temperature, oxidized carbon black (OCB) with the ability of photothermal conversion is introduced into SMPU, which can not only endow SMPU with near-infrared response shape recovery characteristics, but also enhance phase separation degree and mechanical properties of them. SMPU/OCB composites show excellent shape memory effect and rapid photothermal response, and they can be degraded by chymotrypsin with an adjustable degradation rate. These SMPU/OCB composites show broad potential for application as intestinal stents.
Assuntos
Poliuretanos , Materiais Inteligentes , Poliuretanos/química , Quimotripsina , Materiais Biocompatíveis/química , TemperaturaRESUMO
The hydrolysis of a newly synthesized polyether urethane (PEU) that uses polydimethylsiloxane (PDMS) as a second macrodiol and fluorinated diol (FDO) as another chain extender has been studied via immersion in buffer solutions at 70 °C. The hydrolysis process was monitored using scanning electron microscopy (SEM), gel permeation chromatography (GPC), and tensile testing. After aging for 32 weeks, no surface defect was observed on the fluorinated silicon-containing PEUs (FSPEU). Meanwhile, the addition of FDO did not alter the other issues of bulk hydrolysis, such as the changes in molecular weight and mechanical strength. Moreover, microphase separation of FSPEU was suppressed during temperature-accelerated hydrolysis, whereas aging induced a more noticeable phase of morphological change in silicon-modified PEUs (SPEU) due to the hindrance effect of the fluorinated side chains. The formation of hydrolysis-prone allophanate is also reduced in the presence of FDO. FSPEU with enhanced antihydrolysis performance can potentially be applied to biostable medical devices.
Assuntos
Materiais Biocompatíveis , Silício , Hidrólise , Teste de Materiais , Microscopia Eletrônica de Varredura , PoliuretanosRESUMO
Biodegradable polycaprolactone (PCL) has been widely applied as a scaffold material in tissue engineering. However, the PCL surface is hydrophobic and adsorbs nonspecific proteins. Some traditional antifouling modifications using hydrophilic moieties have been successful but inhibit cell adhesion, which is not ideal for tissue engineering. The PCL surface is modified with bioinspired zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) via surface-initiated atom transfer radical polymerization to improve cell adhesion through the unique interaction between choline phosphate (CP, on PMCP) and phosphate choline (PC, on cell membranes). The hydrophilicity of the PCL surface is significantly enhanced after surface modification. The PCL-PMCP surface reduces nonspecific protein adsorption (e.g., up to 91.7% for bovine serum albumin) due to the zwitterionic property of PMCP. The adhesion and proliferation of bone marrow mesenchymal stem cells on the modified surface is remarkably improved, and osteogenic differentiation signs are detected, even without adding any osteogenesis-inducing supplements. Moreover, the PCL-PMCP films are more stable at the early stage of degradation. Therefore, the PMCP-functionalized PCL surface promotes cell adhesion and osteogenic differentiation, with an antifouling background, and exhibits great potential in tissue engineering.
Assuntos
Incrustação Biológica , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Poliésteres/farmacologia , Ácidos Polimetacrílicos/farmacologia , Engenharia Tecidual , Adsorção , Animais , Animais Recém-Nascidos , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Fosforilcolina/síntese química , Fosforilcolina/farmacologia , Espectroscopia Fotoeletrônica , Poliésteres/síntese química , Ácidos Polimetacrílicos/síntese química , Ratos Sprague-Dawley , Propriedades de Superfície , Água/químicaRESUMO
A global transcriptional regulator, MgrA, was previously identified as a key determinant of virulence in Staphylococcus aureus. An 80% EtOH extract of Uncaria gambier was found to attenuate the virulence of S. aureus via its effects on MgrA. Using bioassay-guided fractionation, a polyphenolic polymer, uncariitannin, was found to be the main bioactive constituent of the extract, and its structure was characterized using spectral and chemical analysis. The molecular weight and polydispersity of uncariitannin were determined by gel permeation chromatography-refractive index-light scattering analysis. An electrophoretic mobility shift assay showed that uncariitannin could effectively inhibit the interaction of MgrA with DNA in a dose-dependent manner. Treatment with uncariitannin could decrease the mRNA and protein levels of Hla in both the S. aureus Newman and USA300 LAC strains. Further analysis of Hla expression levels in the Newman ΔmgrA and Newman ΔmgrA/pYJ335-mgrA strains indicated that uncariitannin altered Hla expression primarily in an MgrA-dependent manner. A mouse model of infection indicated that uncariitannin could attenuate MRSA virulence. In conclusion, uncariitannin may be a potential candidate for further development as an antivirulence agent for the treatment of S. aureus infection.
Assuntos
Antibacterianos , Polímeros , Polifenóis , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Uncaria , Virulência/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Feminino , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos Endogâmicos BALB C , Miocárdio/patologia , Polímeros/farmacologia , Polímeros/uso terapêutico , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Baço/efeitos dos fármacos , Baço/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidadeRESUMO
A cross-linked waterborne polyurethane (CPTMGPU) with long-term stability was developed from poly(ethylene glycol) (PEG), polyoxytetramethylene glycol (PTMG), isophorone diisocyanate (IPDI), l-lysine, and its derivative diamine consisting of gemini quaternary ammonium salt (GQAS), using ethylene glycol diglycidyl ether (EGDE) as a cross-linker. Weight loss test, X-ray photoelectron spectroscopy (XPS) measurements, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were performed to prove the surface structure and stability of these CPTMGPU films. Furthermore, the GQAS-bearing CPTMGPUs show repeatable contact-active antibacterial efficacy against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria and do not show any inhibition effect against fibroblasts in vitro. After subcutaneous implantation in rats, the CPTMGPU films manifest good biocompatibility in vivo, despite the presence of a typical foreign body reaction toward surrounding tissues and mild systematic inflammation reaction that could be eliminated after a short implantation period, as demonstrated by histology and immunohistochemistry combined with interleukin (IL)-1ß, IL-4, IL-6, IL-10, and TNF-α analysis though enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR). Therefore, these cross-linked waterborne polyurethanes hold great promise for antibacterial applications in vivo.
Assuntos
Antibacterianos/química , Materiais Biocompatíveis/química , Hidrogéis/química , Compostos de Amônio Quaternário/química , Tensoativos/química , Animais , Antibacterianos/síntese química , Antibacterianos/toxicidade , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Reagentes de Ligações Cruzadas/química , Citocinas/sangue , Escherichia coli/efeitos dos fármacos , Reação a Corpo Estranho/etiologia , Hidrogéis/síntese química , Hidrogéis/toxicidade , Isocianatos/química , Masculino , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus/efeitos dos fármacosRESUMO
The degradation behaviors including oxidation and hydrolysis of silicone modified polycarbonate urethanes were thoroughly investigated. These polyurethanes were based on polyhexamethylene carbonate (PHMC)/polydimethylsiloxane (PDMS) mixed macrodiols with molar ratio of PDMS ranging from 5% to 30%. It was proved that PDMS tended to migrate toward surface and even a small amount of PDMS could form a silicone-like surface. Macrophages-mediated oxidation process indicated that the PDMS surface layer was desirable to protect the fragile soft PHMC from the attack of degradative species. Hydrolysis process was probed in detail after immersing in boiling buffered water using combined analytical tools. Hydrolytically stable PDMS could act as protective shields for the bulk to hinder the chain scission of polycarbonate carbonyls whereas the hydrolysis of urethane linkages was less affected. Although the promoted phase separation at higher PDMS fractions lead to possible physical defects and mechanical compromise after degradation, simultaneously enhanced oxidation and hydrolysis resistance could be achieved for the polyurethanes with proper PDMS incorporation.
Assuntos
Dimetilpolisiloxanos , Macrófagos/metabolismo , Cimento de Policarboxilato , Poliésteres , Poliuretanos , Animais , Dimetilpolisiloxanos/farmacocinética , Dimetilpolisiloxanos/farmacologia , Hidrólise , Macrófagos/citologia , Camundongos , Oxirredução , Cimento de Policarboxilato/química , Cimento de Policarboxilato/farmacocinética , Cimento de Policarboxilato/farmacologia , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Poliuretanos/química , Poliuretanos/farmacocinética , Poliuretanos/farmacologia , Células RAW 264.7RESUMO
Current implant materials have widespread clinical applications together with some disadvantages, the majority of which are the ease with which infections are induced and difficulty in exhibiting biocompatibility. For the efficient improvement of their properties, the development of interface multifunctional modification in a simple, universal, and environmently benign approach becomes a critical challenge and has acquired the attention of numerous scientists. In this study, a lysozyme-polyphosphate composite coating was fabricated for titanium(Ti)-based biomaterial to obtain a multifunctional surface. This coating was easily formed by sequentially soaking the substrate in reduced-lysozyme and polyphosphate solution. Such a composite coating has shown predominant antibacterial activity against Gram-negative bacteria ( E. coli) and improved cell adhesion, proliferation, and differentiation, which are much better than those of the pure substrate. This facile modification endows the biomaterial with anti-infective and potential bone-regenerative performance for clinical applications of biomaterial implants.
Assuntos
Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Muramidase/química , Nanoestruturas/química , Polifosfatos/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Escherichia coli/efeitos dos fármacos , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Próteses e Implantes , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Titânio/químicaRESUMO
Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP-PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering.
Assuntos
Fosforilcolina/química , Adsorção , Adesão Celular , Células Cultivadas , Humanos , Metacrilatos , Polimerização , Polímeros , Propriedades de SuperfícieRESUMO
Shape-memory polymers are highly desirable in implant biomaterials for minimally invasive surgical procedures. However, most of them lack suitable transition temperature, mechanical properties, and biodegradability. Here, a series of shape-memory polyurethanes are synthesized by postcrosslinking in hard-segment domains using a flexible crosslinker. The materials used are all nontoxic and biodegradable. Through postcrosslinking of unsaturated linear polyurethanes with flexible and biodegradable crosslinker, the crosslinked polyurethanes (CPUs) show good mechanical properties, excellent shape-memory property, and repeatability. The post-crosslinking structure and shape-memory mechanism of CPUs are investigated by Fourier transform infrared spectroscopy, differential scanning calorimetry, and dynamic mechanical analysis tests. The crosslinker endows the fixed phase enough crosslinking and inserts in the hard segments to give the fixed phase certain elasticity. The elastic hard segments make them form more hydrogen bonds with soft segments during shape deformation. The low-molecular-weight poly (ε-caprolactone) offers the samples a shape-memory transition temperature at around 37 °C, which is suitable for implant devices in vivo. This work expands CPUs with an elastic crosslinking structure as potential candidates for implant biomaterials. Since the post-crosslinking polymerization is facile, it can be convenient for industrial production.
Assuntos
Materiais Biocompatíveis/química , Poliuretanos/química , Varredura Diferencial de Calorimetria , Ligação de Hidrogênio , Teste de MateriaisRESUMO
A challenge in the development of multifunctional drug delivery systems is to establish a reasonable and effective synthetic route for multifunctional polymer preparation. Herein, we propose a unique protocol to prepare multifunctional micelles by a cross-assembly process using three different functional polyurethanes incorporating acidic sensitive hydrazone, folic acid for active targeting, and gemini quaternary ammonium (GQA) as efficient cell uptake ligands, respectively. These multifunctional mixed micelles (GFHPMs) have been endowed tunable particle sizes and zeta potential and a unique three-order-layer cross-assemble structure. Their drug-loading contents have been significantly improved, and drug release profiles displayed controlled release of their payloads under acid condition. The folate and GQA ligands showed a synergistic effect to enhance the cell uptake. Biodistribution and antitumor effect of these micelles were systematically investigated in vivo, the mixed micelles could penetrate into the depths of tumors, and drug concentrations in tumors reached the maximum of 6.5% ID/g at 24 h, resulting in an excellent therapeutic effect that the volumes of tumors treated with GFHPM are five times smaller than those treated with blank micelles. Our present work provides an effective approach to the design of multifunctional nanocarriers for tumor-targeted and programmed intracellular drug delivery.
Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Polímeros/farmacologia , Poliuretanos/química , Animais , Apoptose/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Neoplasias/patologia , Polímeros/administração & dosagem , Polímeros/química , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND The aim of this study was to investigate the proliferation, differentiation, and tube formation of human outgrowth endothelial progenitor cells (OECs) cultured with porous demineralized bone matrix (DBM) under a dynamic perfusion system in vitro. MATERIAL AND METHODS OECs were isolated, expanded, characterized, eGFP-transfected and seeded on DBM scaffold and cultured under static or dynamic perfusion conditions, and continuously observed under fluorescence microscope. DBM scaffolds were harvested on day six for RT-PCR and western blot assay to analyze the mRNA and protein expression level of CD34, VE-cadherin, and VEGF. Scanning electron microscope (SEM) was used to observe the tube formation of OECs seeded on DBM scaffolds. RESULTS The results showed the cell density of OECs on DBM was higher when exposed to shear stress generated by a dynamic perfusion system. Shear stress also markedly increased the expression level of VE-cadherin and VEGF and decreased the expression of CD34, at both mRNA and protein levels. SEM showed that the shear-stressed OECs formed tube-like structures inside the pores of DBM scaffolds. CONCLUSIONS A dynamic perfusion system can be used as an innovative method for the rapid vascularization in tissue engineering, which can accelerate the proliferation and differentiation of OECs and the vascularization of implanted scaffolds.
Assuntos
Técnicas de Cultura de Células/métodos , Células Progenitoras Endoteliais/citologia , Engenharia Tecidual/métodos , Materiais Biocompatíveis , Matriz Óssea/citologia , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Células Progenitoras Endoteliais/transplante , Humanos , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/fisiologia , Osteogênese/fisiologia , Perfusão , Estresse Mecânico , Alicerces TeciduaisRESUMO
In this paper, to investigate the effects of interactions between poly(quaternary ammonium) salts (PQAs) and poly(ethylene glycol) on their mixed micellar surface structures and properties under spontaneous conditions, a series of PQAs were first designed and synthesized by atom transfer radical polymerization (ATRP) using 2-(dimethylamino) ethyl methacrylate (DMAEMA) quaternized by bromobutane, bromooctane, and bromododecane, respectively. Poly(poly(ethylene glycol) methyl ether methacrylate) (PPEG) with a similar degree of polymerization was also prepared using poly(ethylene glycol) methyl ether methacrylate by ATRP. Next, these PQAs were mixed with an equal weight of PPEG in water to cross-assemble into mixed micelles. The structures and features of these mixed micelles were characterized by fluorescence measurements, transmission electron microscopy (TEM), dynamic light scattering (DLS), phase analysis light scattering (PALS), proton nuclear magnetic resonance ((1)H NMR), and hydrogen-hydrogen correlation spectroscopy nuclear magnetic resonance (H-H COSY NMR). These results suggest that PQAs and PPEG mixtures can cross-assemble into mixed micelles with low CMC. The surface structures, particle sizes, size distributions, and zeta potentials of PQAs and PPEG mixtures can be tailored by varying the alkyl chain length in quaternary ammonium salts, and the alkyl chain length also influences the distribution and the alkyl chain orientation of quaternary ammonium salts on mixed micelle surfaces. In addition, cytotoxicity of these mixed micelles can be markedly reduced by PPEG compared with their corresponding PQAs, but their good antibacterial activities are still maintained to a certain degree, as evaluated by methyl tetrazolium assay (MTT) and minimum inhibitory concentration (MIC). Our present work provides a new avenue for the preparation of biocompatible and antibacterial materials for biomedical applications.
Assuntos
Micelas , Poliaminas/química , Polietilenoglicóis/química , Alcanos/química , Difusão Dinâmica da Luz , Espectroscopia de Ressonância Magnética , Metacrilatos/síntese química , Metacrilatos/química , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Polieletrólitos , Polietilenoglicóis/síntese química , Compostos de Amônio Quaternário/químicaRESUMO
Infection of open tibial fractures with contamination remains a challenge for orthopedic surgeons. Local use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads and blocks is a widely used procedure to reduce the risk of infection. However, the development of antibiotic-resistant organisms make the management of infection more difficult. Our in vitro study demonstrated that quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan [HACC])-loaded PMMA bone cement exhibits strong antibacterial activity toward antibiotic-resistant bacteria. Therefore, the present study aimed to investigate the in vivo antibacterial activity of quaternized chitosan-loaded PMMA. Twenty-four adult female New Zealand White rabbits were used in this study. The right proximal tibial metaphyseal cavity was prepared, 10(7) CFU of methicillin-resistant Staphylococcus epidermidis was inoculated, and PMMA-only, gentamicin-loaded PMMA (PMMA-G), chitosan-loaded PMMA (PMMA-C), or HACC-loaded PMMA (PMMA-H) bone cement cylinders were inserted. During the follow-up period, the infections were evaluated using X rays on days 21 and 42 and histopathological and microbiological analyses on day 42 after surgery. Radiographic indications of bone infections, including bone lysis, periosteal reactions, cyst formation, and sequestral bone formation, were evident in the PMMA, PMMA-G, and PMMA-C groups but not in the PMMA-H group. The radiographic scores and gross bone pathological and histopathological scores were significantly lower in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups (P < 0.05). Explant cultures also indicated significantly less bacterial growth in the PMMA-H group than in the PMMA, PMMA-G, and PMMA-C groups (P < 0.01). We concluded that PMMA-H bone cement can inhibit the development of bone infections in this animal model inoculated with antibiotic-resistant bacteria, thereby demonstrating its potential application for treatment of local infections in open fractures.
Assuntos
Cimentos Ósseos/química , Cimentos Ósseos/uso terapêutico , Quitosana/química , Epiderme/microbiologia , Polimetil Metacrilato/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/patogenicidade , Tíbia/microbiologia , Animais , Feminino , Resistência a Meticilina , CoelhosRESUMO
A cell internalizable and intracellularly degradable micellar system, assembled from multiblock polyurethanes bearing cell-penetrating gemini quaternary ammonium pendent groups in the side chain and redox-responsive disulfide linkages throughout the backbone, was developed for potential magnetic resonance imaging (MRI) and drug delivery. The nanocarrier is featured as a typical "cleavable core-internalizable shell-protective corona" architecture, which exhibits small size, positive surface charge, high loading capacity, and reduction-triggered destabilization. Furthermore, it can rapidly enter tumor cells and release its cargo in response to an intracellular level of glutathione, resulting in enhanced drug efficacy in vitro. The magnetic micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles demonstrate excellent MRI contrast enhancement, with T2 relaxivity found to be affected by the morphology of SPIO-clustering inside the micelle core. The multifunctional carrier with good cytocompatibility and nontoxic degradation products can serve as a promising theranostic candidate for efficient intracellular delivery of anticancer drugs and real-time monitoring of therapeutic effect.
Assuntos
Antineoplásicos , Meios de Contraste , Portadores de Fármacos , Compostos Férricos , Micelas , Poliuretanos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Poliuretanos/química , Poliuretanos/farmacologiaRESUMO
Glioblastoma (GBM) is a common primary brain malignancy known for its ability to invade the brain, resistance to chemotherapy and radiotherapy, tendency to recur frequently, and unfavorable prognosis. Attempts have been undertaken to create 2D and 3D models, such as glioblastoma organoids (GBOs), to recapitulate the glioma microenvironment, explore tumor biology, and develop efficient therapies. However, these models have limitations and are unable to fully recapitulate the complex networks formed by the glioma microenvironment that promote tumor cell growth, invasion, treatment resistance, and immune escape. Therefore, it is necessary to develop advanced experimental models that could better simulate clinical physiology. Here, we review recent advances in natural biomaterials (mainly focus on collagen and its derivatives)-based GBO models, as in vitro experimental platforms to simulate GBM tumor biology and response to tested drugs. Special attention will be given to 3D models that use collagen, gelatin, further modified derivatives, and composite biomaterials (e.g., with other natural or synthetic polymers) as substrates. Application of these collagen/derivatives-constructed GBOs incorporate the physical as well as chemical characteristics of the GBM microenvironment. A perspective on future research is given in terms of current issues. Generally, natural materials based on collagen/derivatives (monomers or composites) are expected to enrich the toolbox of GBO modeling substrates and potentially help to overcome the limitations of existing models.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia , Organoides , Neoplasias Encefálicas/tratamento farmacológico , Colágeno/uso terapêutico , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Microambiente TumoralRESUMO
Underwater adhesives with injectable, organic solvent-free, strong, fast adhesion, and hemostatic properties have become an urgent need in biomedical field. Herein, a novel polyurethane underwater adhesive (PUWA) inspired by mussels is developed utilizing the rapid post-cure reaction of isocyanate esterification without organic solvents. The PUWA is created through the injectable two component curing process of component A (biocompatible polyurethane prepolymer) and component B (dopamine modified lysine derivatives: chain extender-LDA and crosslinker-L3DA). The two-component adhesive cures quickly and firmly underwater, with an impressive bonding strength of 40 kPa on pork skin and excellent burst pressure of 394 mmHg. Moreover, the PUWA exhibits robust adhesion strength in hostile environments with acid, alkali and saline solutions. Combined with excellent biocompatibility and hemostatic performance, the PUWA demonstrates effectively sealing wounds and promoting healing. With the ability to bond diverse substrates rapidly and strongly, the PUWA holds significant potential for application in both biomedical and industrial fields.
Assuntos
Adesivos , Hemostáticos , Poliuretanos , Poliuretanos/química , Animais , Adesivos/química , Hemostáticos/química , Hemostáticos/farmacologia , Teste de Materiais , Cicatrização/efeitos dos fármacos , Materiais Biocompatíveis/química , Suínos , Adesivos Teciduais/químicaRESUMO
Ice-templated porous biomaterials possess transformative potential in regenerative medicine; yet, scaling up ice-templating processes for broader applications-owing to inconsistent pore formation-remains challenging. This study reports an innovative semi-solid freeze-casting technique that draws inspiration from semi-solid metal processing (SSMP) combined with ice cream-production routines. This versatile approach allows for the large-scale assembly of various materials, from polymers to inorganic particles, into isotropic 3D scaffolds featuring uniformly equiaxed pores throughout the centimeter scale. Through (cryo-)electron microscopy, X-ray tomography, and finite element modeling, the structural evolution of ice grains/pores is elucidated, demonstrating how the method increases the initial ice nucleus density by pre-fabricating a semi-frozen slurry, which facilitates a transition from columnar to equiaxed grain structures. For a practical demonstration, as-prepared scaffolds are integrated into a bilayer tissue patch using biodegradable waterborne polyurethane (WPU) for large-scale oral mucosal reconstruction in minipigs. Systematic analyses, including histology and RNA sequencing, prove that the patch modulates the healing process toward near-scarless mucosal remodeling via innate and adaptive immunomodulation and activation of pro-healing genes converging on matrix synthesis and epithelialization. This study not only advances the field of ice-templating fabrication but sets a promising precedent for scaffold-based large-scale tissue regeneration.
Assuntos
Congelamento , Mucosa Bucal , Alicerces Teciduais , Alicerces Teciduais/química , Animais , Porosidade , Suínos , Engenharia Tecidual/métodos , Porco Miniatura , Poliuretanos/química , Materiais Biocompatíveis/química , Gelo , Medicina Regenerativa/métodosRESUMO
Postoperative adhesions, a prevalent complication following abdominal surgery, affect 90% of patients undergoing abdominal surgical procedures. Currently, the primary approach to prevent postoperative adhesions involves physical isolation of the surgical site and surrounding tissues using a hydrogel; however, this method represents a rudimentary strategy. Herein, considering the impact of oxidative stress and free radicals on postoperative adhesion during wound healing, an injectable antioxidant hydrogel, named PU-OHA-D, was successfully synthesized, which is formed by the crosslinking of dopamine-modified oxidized hyaluronic acid (OHA-D) and dihydrazide-terminated polyurethane (PU-ADH) through hydrazone bonding. PU-OHA-D hydrogel possesses versatile characteristics such as rapid gel formation, injectability, self-repair capability and biodegradability. Additionally, they exhibit an excellent ability to clear free radicals and superior tissue adhesion. PU-OHA-D can be injected in situ to form a hydrogel to prevent abdominal wall-cecum adhesion. Importantly, it can effectively eliminate free radicals and inhibit oxidative stress at the wound site. Thereby, it leads to collagen physiological degradation and prevents the occurrence of postoperative adhesions. The bioinspired hydrogel demonstrates its great potential in preventing postoperative adhesion and promoting wound healing.