Preparation and performance of gelatin modified by methacrylic anhydride/treated dentin matrix bioactive scaffolds / 中国组织工程研究

BACKGROUND:Pulp regeneration has been a hot and difficult research topic in recent years,and the construction of composite bio-scaffolding materials provides new ideas and methods for pulp regeneration. OBJECTIVE:To observe the effect of freeze-dried gelatin modified by methacrylic anhydride/treated dentin matrix bioactive scaffolds on proliferation,migration,and osteogenic differentiation of human dental pulp stem cells. METHODS:The mass ratios of gelatin modified by methacrylic anhydride and treated dentin matrix at 2:1,1:1 and 1:2 were obtained by dispersing different masses of treated dentin matrix into gelatin modified by methacrylic anhydride solution.The gelatin modified by methacrylic anhydride/treated dentin matrix bioactive scaffolds were prepared by vacuum freeze-drying.The microstructure,water absorption,and mechanical properties of the scaffolds were measured.Human dental pulp stem cells were cultured with different mass ratios of scaffold extract and DMEM(control group)to detect cell proliferation and migration.Human dental pulp stem cells were cultured with different mass ratios of scaffold extract + osteogenic induction solution and DMEM + osteogenic induction solution(control group),and their osteogenic ability was analyzed by alkaline phosphatase staining. RESULTS AND CONCLUSION:(1)Under scanning electron microscopy,the scaffolds of the three groups all had porous structures.The porosity of the scaffolds increased with the increase of treated dentin matrix quality,and there was significant difference between the two groups(P＜0.05).The water absorption of scaffolds increased with the increase of treated dentin matrix mass,and there was significant difference between groups(P＜0.05).The compressive strength and shear strength of the scaffold increased with the increase of the mass of treated dentin matrix.(2)CCK-8 assay showed that after 3,5,and 7 days of culture,the cell proliferation absorbance values in the 2:1,1:1,and 1:2 scaffold groups were higher than those in the control group(P＜0.05).The cell proliferation absorbance values increased with the increase of treated dentin matrix mass in the scaffold(P＜0.05).The cell scratch test showed that the cell migration rate in the 2:1,1:1,and 1:2 scaffold groups was higher than that in the control group(P＜0.05),and the cell migration rate increased with the increase of treated dentin matrix mass in the scaffold(P＜0.05).(3)Alkaline phosphatase staining showed that the osteogenic differentiation ability of cells in the 2:1,1:1,and 1:2 scaffold groups was stronger than that in the control group,and the osteogenic ability of cells was enhanced with the increase of treated dentin matrix mass in the scaffold.(4)The results showed that the scaffold with a mass ratio of 1:2 between gelatin modified by methacrylic anhydride and treated dentin matrix was the most suitable for the proliferation and differentiation of dental pulp stem cells.

Validação biológica de grânulos de vidro bioativas (compostos por biovidro 45S5): estudo in vitro e in vivo / Biological validation of bioactive glass granules (composed of 45S5 bioglass): in vitro and in vivo study

O tecido ósseo, embora tenha a capacidade de regeneração, é limitado em sua eficácia diante de defeitos críticos que impedem a regeneração natural. Dessa forma, materiais como a hidroxiapatita (HA) têm sido considerados promissores na engenharia de tecido ósseo. Contudo, apesar de sua ampla utilização, a hidroxiapatita apresenta desvantagens, como a taxa de reabsorção e remodelação lenta. Em contraste, o biovidro 45S5 se destaca por sua biocompatibilidade, propriedades bioativas e degradabilidade. Este estudo objetivou avaliar o comportamento biológico in vitro e in vivo de grânulos de vidro bioativas de biovidro 45S5 fabricadas pelo método de fusão. Os biovidros foram caracterizados por meio da difração de raios X (DRX), espectroscopia de infravermelho por transformação de Fourier (FTIR), calorimetria diferencial de varredura (DSC) e espectrometria de emissão óptica com plasmas indutivamente acoplados (ICP OES). Em seguida, foi realizado o estudo in vitro, utilizando células osteoblásticas isoladas de fêmures de ratos, que foram submetidas a análise da morfologia celular (MEV), viabilidade celular (MTT), conteúdo de proteína total (PT), atividade de fosfatase alcalina (ALP) e formação de nódulos de mineralização. No estudo in vivo, foram realizados defeitos ósseos críticos de 7 mm na tíbia de coelhos da raça New Zealand, que foram divididos em dois grupos (n=6) de acordo com o material de preenchimento: hidroxiapatita comercial (HA) e biovidro 45S5 (BG45S5). Após 2, 8 e 12 semanas, os animais foram eutanasiados e as peças ósseas foram submetidas as análises histológicas e histomorfométricas. Os dados foram submetidos ao teste de normalidade Shapiro-Wilk (p=0,05) e quando normais realizamos o teste t de student e quando não normais realizamos o teste de Mann-Whitney. Os resultados dos testes físico-químicos mostraram sucesso na produção do novo biomaterial. Nos testes in vitro, observou-se que o grupo BG45S5 não apresentou citotoxicidade e mostrou-se promissor com diferença estatisticamente significante em relação ao grupo hidroxiapatita comercial (p=0.0263). Nos testes de PT, ALP e nódulos de mineralização, os grupos não apresentaram diferença estatística entre eles (p<0,05). Contudo, o grupo BG45S5 mostrou-se promissor em relação aos outros grupos. Na análise histológica, ambos os grupos apresentaram neoformação óssea nos defeitos após 2, 8 e 12 semanas. Na histomorfometria, observou-se que os grupos BG45S5 e HA apresentaram maior área de neoformação óssea em 12 semanas. Houve diferença estatisticamente significante entre os grupos no tempo de 2 semanas, com maior neoformação para o grupo BG45S5. Apesar dos resultados promissores do grupo BG45S5, não houve diferença estatisticamente significativa entre os grupos (p<0,05) nos tempos de 8 e 12 semanas. Em resumo, os resultados evidenciaram o sucesso na produção do biomaterial sintético e o potencial do biomaterial BG45S5 como um material promissor para tratamento de defeitos ósseos críticos. (AU)

Bone tissue, despite its capacity of regeneration, is limited in its effectiveness when faced with critical defects that prevent natural regeneration. Therefore, materials such as hydroxyapatite (HA) have been considered promising in bone tissue engineering. However, despite its wide use, hydroxyapatite has disadvantages, such as slow resorption and remodeling rates. In contrast, 45S5 bioglass stands out for its biocompatibility, bioactive properties and degradability. This study aimed to evaluate the in vitro and in vivo biological behavior of bioactive 45S5 bioglass beads manufactured by the melt quenched method. The bioglasses were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and inductively coupled plasma optical emission spectrometry (ICP OES). Following this, an in vitro study was conducted using osteoblastic cells isolated from rat femurs, which were subjected to analysis of cell morphology (SEM), cell viability (MTT), total protein content (TP), alkaline phosphatase activity (ALP) and mineralization nodule formation. In the in vivo study, critical bone defects of 7 mm were created in the tibia of New Zealand rabbits, which were divided into two groups (n=6) according to the filling material: commercial hydroxyapatite (HA) and bioactive glass 45S5 (BG45S5). After 2, 8, and 12 weeks, the animals were euthanized and the bone pieces were subjected to histological and histomorphometric analyses. Data were subjected to the Shapiro-Wilk normality test (p=0.05), and when normal, we performed the Student's t-test, and when non-normal, we performed the Mann-Whitney test. The results of the physicochemical tests showed success in the production of the new biomaterial. In the in vitro tests, it was observed that the BG45S5 group did not present cytotoxicity and showed promise with a statistically significant difference compared to the commercial hydroxyapatite group (p=0.0263). In the TP, ALP and mineralization nodule tests, the groups showed no statistical difference between them (p<0.05). However, the BG45S5 group showed promise compared to the other groups. In the histological analysis, both groups showed new bone formation in the defects after 2, 8, and 12 weeks. In the histomorphometric analysis, it was observed that the BG45S5 and HA groups presented a larger area of new bone formation at 12 weeks. There was a statistically significant difference between the groups at 2 weeks, with greater new formation for the BG45S5 group. Despite the promising results of the BG45S5 group, there was no statistically significant difference between the groups (p<0.05) at 8 and 12 weeks. In summary, the results evidenced the successful production of the synthetic biomaterial and the potential of the BG45S5 bioglass as a promising material for treating critical bone defect.(AU)

Cytotoxicity of dilutions of bioceramic materials in stem cells of human exfoliated deciduous teeth

Abstract Several materials have been developed to preserve pulp vitality. They should have ideal cytocompatibility characteristics to promote the activity of stem cells of human exfoliated deciduous teeth (SHED) and thus heal pulp tissue. Objective To evaluate the cytotoxicity of different dilutions of bioceramic material extracts in SHED. Methodology SHED were immersed in αMEM + the material extract according to the following experimental groups: Group 1 (G1) -BBio membrane, Group 2 (G2) - Bio-C Repair, Group 3 (G3) - MTA Repair HP, Group 4 (G4) - TheraCal LC, and Group 5 (G5) - Biodentine. Positive and negative control groups were maintained respectively in αMEM + 10% FBS and Milli-Q Water. The methods to analyze cell viability and proliferation involved MTT and Alamar Blue assays at 24, 48, and 72H after the contact of the SHED with bioceramic extracts at 1:1 and 1:2 dilutions. Data were analyzed by the three-way ANOVA, followed by Tukey's test (p<0.05). Results At 1:1 dilution, SHED in contact with the MTA HP Repair extract showed statistically higher cell viability than the other experimental groups and the negative control (p<0.05), except for TheraCal LC (p> 0.05). At 1:2 dilution, BBio Membrane and Bio-C showed statistically higher values in intra- and intergroup comparisons (p<0.05). BBio Membrane, Bio-C Repair, and Biodentine extracts at 1:1 dilution showed greater cytotoxicity than 1:2 dilution in all periods (p<0.05). Conclusion MTA HP Repair showed the lowest cytotoxicity even at a 1:1 dilution. At a 1:2 dilution, the SHED in contact with the BBio membrane extract showed high cell viability. Thus, the BBio membrane would be a new non-cytotoxic biomaterial for SHED. Results offer possibilities of biomaterials that can be indicated for use in clinical regenerative procedures of the dentin-pulp complex.

Preservação óssea alveolar pós exodontia: objetivos, opções técnicas, vantagens e desvantagens / Alveolar bone preservation after tooth extraction: objectives, technical options, advantages and disadvantages

A extração do elemento dentário promove uma série de eventos biológicos que resultam no colapso da estrutura alveolar, ocasionando a perda óssea volumétrica na região de extração. Preservar esse alvéolo dentário é imprescindível para uma boa reabilitação dentária do paciente. Objetivo: Realizar uma revisão de literatura abordando os objetivos, opções técnicas, vantagens e desvantagens da preservação óssea alveolar pós extração. Materiais e métodos: Foi feita uma revisão de literatura utilizando as bases de dados Biblioteca Virtual em Saúde (BVS), PubMed e Google acadêmico, usando os descritores "extração dentária", "perda do osso alveolar", "regeneração óssea". Foram incluídos 34 artigos. Resultados: A preservação alveolar pós extração começa desde a realização de uma técnica cirúrgica menos invasiva até a colocação de enxertos do tipo autógenos, alógenos, xenógenos, aloplásticos e biomateriais promotores de cicatrização e reparação tecidual. Conclusão: Existe na literatura atual uma vasta gama de textos científicos que abordam técnicas de preservação alveolar pós exodontia, com distintas respostas teciduais. Todavia, nenhum biomaterial listado nesta revisão contém todas as características que proporcionam regeneração completa do osso alveolar após exodontia(AU)

The extraction of the dental element promotes a series of biological events that results in the collapse of the alveolar structure, causing volumetric bone loss in the region of extraction. Preserving this dental alveolus is essential for a good dental rehabilitation of the patient. Objective: To conduct a literature review addressing the objectives, technical options, advantages and disadvantages of post-extraction alveolar bone preservation. Materials and methods: A literature review was carried out using the Virtual Health Library (VHL), PubMed and academic Google databases, using the descriptors "tooth extraction", "alveolar bone loss", "bone regeneration". 34 articles were included. Results: Post-extraction alveolar preservation starts from the performance of a less invasive surgical technique to the placement of autogenous, allogeneic, xenogeneic, alloplastic and biomaterials that promote healing and tissue repair. Conclusion: There´s is a wide range of scientific texts in the current literature that address post-extraction alveolar preservation techniques with different tissue responses. However, none of the biomaterials listed in this review contain all the characteristics that provide complete regeneration of alveolar bone after extraction(AU)

A Review on the Advances of Biocompatible Materials and Their Processing Via Additive Manufacturing for Tissue Engineering Applications / Una Revisión de los Avances en Materiales Biocompatibles y su Procesamiento Mediante Manufactura Aditiva Para Aplicaciones en Ingeniería de Tejidos

Abstract: About two decades ago, medicine experienced a revolutionary approach, driven by technological development in manufacturing techniques and scientific advances in the medical and life sciences, the field took on the challenge of regenerating tissue and organs damaged by disease, trauma, or hereditary issues, incorporating additive manufacturing as one of its strategies. Since its inception, regenerative medicine has developed techniques like tissue engineering, cellular therapy, medical devices, and artificial organs to provide wound healing and orthopedic applications. The incorporation of additive manufacturing allowed to recreate biologically appropriate environments for cell reproduction and growth that, eventually, lead to useful, regenerated tissue or organs. The objective of the present work is to review recent advances in the application of additive manufacturing techniques and ad hoc biomaterials in the field of regenerative medicine, to determine their impact in the development of new therapies for tissue engineering.

Resumen: Hace aproximadamente dos décadas, la medicina experimentó un enfoque revolucionario, impulsado por el desarrollo tecnológico en técnicas de fabricación y los avances científicos en las ciencias médicas y de la vida. El campo asumió el desafío de regenerar tejidos y órganos dañados por enfermedades, traumatismos o problemas hereditarios, incorporando la fabricación aditiva como una de sus estrategias. Desde su inicio, la medicina regenerativa ha desarrollado técnicas como la ingeniería de tejidos, la terapia celular, los dispositivos médicos y los órganos artificiales para proporcionar cicatrización de heridas y aplicaciones ortopédicas. La incorporación de la fabricación aditiva ha permitido recrear entornos biológicamente apropiados para la reproducción y crecimiento celular, lo que eventualmente ha llevado a la obtención de tejidos u órganos regenerados útiles. El objetivo de este trabajo es revisar los avances recientes en la aplicación de técnicas de fabricación aditiva y biomateriales ad hoc en el campo de la medicina regenerativa, para determinar su impacto en el desarrollo de nuevas terapias para la ingeniería de tejidos.

Estudio de biocompatibilidad de matrices poliméricas combinadas, responsivas al pH, con aplicación en Ingeniería de Tejido Óseo / Biocompatibility study of combined pH-responsive polymeric matrices with application in Bone Tissue Engineering

El presente trabajo muestra la obtención de un material a partir de un polímero sintético (TerP) y otro natural, mediante entrecruzamiento físico y su caracterización fisicoquímica y biológica, con el fin de emplearlos para regeneración de tejido óseo. Las membranas fueron obtenidas por la técnica de evaporación del solvente y caracterizadas por espectroscopia FTIR, ensayos de hinchamiento, medidas de ángulo de contacto y microscopia electrónica de barrido (SEM). Se encontró que la compatibilidad entre los polímeros que la constituyen es estable a pH fisiológico y que, al incorporar mayor cantidad del TerP a la matriz, esta se vuelve más hidrofóbica y porosa. Además, teniendo en cuenta la aplicación prevista para dichos materiales, se realizaron estudios de biocompatibilidad y citotoxicidad con células progenitoras de médula ósea (CPMO) y células RAW264.7, respectivamente. Se evaluó la proliferación celular, la producción y liberación de óxido nítrico (NO) al medio de cultivo durante 24 y 48 horas y la expresión de citoquinas proinflamatorias IL-1ß y TNF-α de las células crecidas sobre los biomateriales variando la cantidad del polímero sintético. Se encontró mayor proliferación celular y menor producción de NO sobre las matrices que contienen menos proporción del TerP, además de poseer una mejor biocompatibilidad. Los resultados de este estudio muestran que el terpolímero obtenido y su combinación con un polímero natural es una estrategia muy interesante para obtener un biomaterial con posibles aplicaciones en medicina regenerativa y que podría extenderse a otros sistemas estructuralmente relacionados. (AU)

In the present work, the preparation of a biomaterial from a synthetic terpolymer (TerP) and a natural polymer, physically crosslinked, is shown. In order to evaluate the new material for bone tissue regeneration, physicochemical and biological characterizations were performed. The membranes were obtained by solvent casting and characterized using FTIR spectroscopy, swelling tests, contact angle measurements, and scanning electron microscopy (SEM). It was found that the compatibility between the polymers is stable at physiological pH and the incorporation of a higher amount of TerP into the matrix increases hydrophobicity and porosity.Furthermore, considering the intended application of these materials, studies of biocompatibility and cytotoxicity were conducted with Bone Marrow Progenitor Cells (BMPCs) and RAW264.7 cells, respectively. Cell proliferation, NO production and release into the culture medium for 24 and 48 hours, and proinflammatory cytokine expression of IL-1ß and TNF-α from cells grown on the biomaterials while varying the amount of the synthetic polymer were evaluated. Greater cell proliferation and lower NO production were found on matrices containing a lower proportion of TerP, in addition to better biocompatibility. The results of this study demonstrate that the obtained terpolymer and its combination with a natural polymer is a highly interesting strategy for biomaterial preparation with potential applications in regenerative medicine. This approach could be extended to other structurally related systems. (AU)

Enxerto ósseo alveolar autógeno associado a biomateriais em fissura lábio palatina / Injerto óseo alveolar autógeno asociado a biomateriales en labio y paladar hendido / Autogenous alveolar bone graft associated with biomaterials in cleft lip and palate

Objetivo: Discutir a utilização do enxerto ósseo autógeno associado a biomateriais na reconstrução de defeito ósseo alveolar em paciente com fissura lábio palatina. Relato de caso: Paciente, 09 anos de idade, em tratamento no Serviço Integrado de Reabilitação de Anomalias Craniofaciais do Hospital São Marcos, Teresina - Piauí - Brasil, apresentando fissura lábio palatina unilateral, completa à esquerda, não sindrômica, submetido à queiloplastia aos 03 meses de idade, e palatoplastia aos 18 meses, resultando como sequela uma fístula oronasal, corrigida cirurgicamente quando a paciente completou 07 anos de idade. Aos 09 anos, realizou-se a cirurgia com enxerto ósseo alveolar, com osso autógeno associado a osso mineral tipo (Bio-Oss, Geistlich), protegido com membrana de colágeno (Bio-Gide, Geistlich) e membrana de Fibrina Rica em Plaqueta (PRF). Conclusão: O enxerto ósseo alveolar utilizando osso autógeno associado a osso mineral bovino, membrana de colágeno e membrana de Fibrina Rica em Plaquetas (PRF) assim como a intervenção cirúrgica na faixa etária citada na literatura mostraram-se eficientes para se atingir o sucesso terapêutico... (AU)

Objetivo: Discutir el uso de injerto óseo autógeno asociado a biomateriales en la reconstrucción del defecto óseo alveolar en un paciente con labio y paladar hendido. Reporte de caso: Paciente de 09 años de edad, en tratamiento en el Servicio Integrado de Rehabilitación de Anomalías Craneofaciales del Hospital São Marcos, Teresina - Piauí - Brasil, presentando labio y paladar hendido unilateral, completo a la izquierda, no sindrómico, sometido a queiloplastia a los 03 meses de edad, y palatoplastia a los 18 meses, resultando como secuela una fístula oronasal, corregida quirúrgicamente cuando el paciente completó 07 años de edad. A los 09 años de edad, se realizó una intervención quirúrgica con injerto óseo alveolar, con hueso autógeno asociado de tipo mineral (Bio-Oss, Geistlich), protegido con membrana de colágeno (Bio-Gide, Geistlich) y Membrana de Fibrina Rica en Plaquetas (PRF). Conclusión: El injerto óseo alveolar utilizando hueso autógeno asociado a hueso mineral bovino, membrana de colágeno y Membrana de Fibrina Rica en Plaquetas (PRF), así como la intervención quirúrgica en el rango de edad citado en la literatura, se mostraron eficientes para lograr el éxito terapéutico... (AU)

Objective: To discuss the use of autogenous bone graft associated with biomaterials in the reconstruction of alveolar bone defect in a patient with cleft lip and palate. Case Report: Patient, 09 years old, under treatment at the Integrated Service for Rehabilitation of Craniofacial Anomalies of the Hospital São Marcos, Teresina - Piauí - Brazil, presenting unilateral cleft lip and palate, complete to the left, not syndromic, underwent cheiloplasty at 03 months of age, and palatoplasty at 18 months, resulting as a sequela an oronasal fistula, surgically corrected when the patient turned 07 years old. At 09 years of age, surgery was performed with alveolar bone grafting, with autogenous bone associated with mineral bone type (Bio-Oss, Geistlich), protected with collagen membrane (Bio-Gide, Geistlich) and Platelet Rich Fibrin (PRF) membrane. Conclusion: Alveolar bone grafting using autogenous bone associated with bovine mineral bone, collagen membrane and Platelet Rich Fibrin Membrane (PRF) as well as surgical intervention in the age range cited in the literature were shown to be efficient in achieving therapeutic success... (AU)

Evaluation of contact angle and mechanical properties of resin monomers filled with graphene oxide nanofibers

Abstract This in vitro study synthesized hybrid nanofibers embedded in graphene oxide (GO) and incorporated them into experimental resin composite monomers to evaluate their physical-mechanical properties. Inorganic-organic hybrid nanofibers were produced with precursor solutions of 1% wt. GO-filled Poly (d,l-lactide, PLA) fibers and scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) characterized the morphology and chemical composition of the spun fibers. Resin composite monomers were developed and a total of 5% nanofibers were incorporated into the experimental materials. Three groups were developed: G1 (control resin monomers), G2 (resin monomers/PLA nanofibers), and G3 (resin monomers/inorganic-organic hybrid nanofibers). Contact angle (n=3), flexural strength (n=22), elastic modulus (n=22), and Knoop hardness (n=6) were evaluated. The mean of the three indentations was obtained for each sample. The normality of data was assessed by QQ Plot with simulated envelopes and analyzed by Welch's method (p<0.05). Overall, SEM images showed the regular shape of nanofibers but were non-aligned. Compositional analysis from EDS (n=6) revealed the presence of carbon and oxygen (present in GO composition) and Si from the functionalization process. The results of contact angle (°) and hardness (Kg/mm2) for each group were as follow, respectively: G1 (59.65±2.90; 37.48±1.86a), G2 (67.99±3.93; 50.56±1.03b) and G3 (62.52±7.40; 67.83±1.01c). The group G3 showed the highest Knoop hardness values (67.83 kg/mm2), and the flexural strength of all groups was adversely affected. The experimental resin composite composed of hybrid nanofibers with GO presented increased hardness values and hydrophilic behavior.

Resumo Este estudo in vitro sintetizou nanofibras híbridas embebidas em óxido de grafeno (GO), incorporando-as à uma resina composta experimental de monômeros para avaliar suas propriedades físico-mecânicas. Nanofibras híbridas inorgânica-orgânicas foram produzidas com soluções precursoras de fibras poli (d, l-lactídeo, PLA) preenchidas com GO a 1% em peso e microscopia eletrônica de varredura (MEV) e espectroscopia de raio-X de energia dispersiva (EDS) caracterizaram a morfologia e composição química das fibras. Monômeros de resina composta foram desenvolvidos e um total de 5% de nanofibras foi incorporado aos materiais experimentais. Três grupos foram desenvolvidos: G1 (monômeros de resina controle), G2 (monômeros de resina/ nanofibras de PLA) e G3 (monômeros de resina/nanofibras híbridas inorgânico-orgânicas). Ângulo de contato (n=3), resistência à flexão (n=22), módulo de elasticidade (n=22) e dureza Knoop (n=6) foram avaliados. A média das três endentações foi obtida para cada amostra. A normalidade dos dados foi avaliada pelo QQ Plot com envelopes simulados e analisada pelo método de Welch (p<0,05). No geral, as imagens de MEV mostraram forma regular de nanofibras, mas não alinhadas. A análise composicional de EDS (n=6) revelou a presença de carbono e oxigênio (presentes na composição do GO) e Si resultante do processo de funcionalização. Os resultados do ângulo de contato (°) e dureza (Kg/mm2) para cada grupo foram os seguintes, respectivamente: G1 (59,65±2,90; 37,48±1,86a), G2 (67,99±3,93; 50,56±1,03b) e G3 (62,52±7,40; 67,83±1,01c). G3 apresentou os maiores valores de dureza Knoop (67,83 kg/mm2), e a resistência à flexão de todos os grupos foi prejudicada. A resina composta experimental composta por nanofibras híbridas com GO apresentou maiores valores de dureza e comportamento hidrofílico.

The degradation of plastics and the production of polyhydroxyalkanoates (PHA) / 生物工程学报

In recent years, the petroleum-based plastic pollution problem has been causing global attention. The idea of "degradation and up-cycling of plastics" was proposed for solving the environmental pollution caused by non-degradable plastics. Following this idea, plastics would be firstly degraded and then reconstructed. Polyhydroxyalkanoates (PHA) can be produced from the degraded plastic monomers as a choice to recycle among various plastics. PHA, a family of biopolyesters synthesized by many microbes, have attracted great interest in industrial, agricultural and medical sectors due to its biodegradability, biocompatibility, thermoplasticity and carbon neutrality. Moreover, the regulations on PHA monomer compositions, processing technology, and modification methods may further improve the material properties, making PHA a promising alternative to traditional plastics. Furthermore, the application of the "next-generation industrial biotechnology (NGIB)" utilizing extremophiles for PHA production is expected to enhance the PHA market competitiveness, promoting this environmentally friendly bio-based material to partially replace petroleum-based products, and achieve sustainable development with carbon-neutrality. This review summarizes the basic material properties, plastic upcycling via PHA biosynthesis, processing and modification methods of PHA, and biosynthesis of novel PHA.

Progress in the application of patch materials in cardiovascular surgery / 中南大学学报(医学版)

The cardiovascular patch, served as artificial graft materials to replace heart or vascular tissue defect, is still playing a key role in cardiovascular surgeries. The defects of traditional cardiovascular patch materials may determine its unsatisfactory long-term effect or fatal complications after surgery. Recent studies on many new materials (such as tissue engineered materials, three-dimensional printed materials, etc) are being developed. Patch materials have been widely used in clinical procedures of cardiovascular surgeries such as angioplasty, cardiac atrioventricular wall or atrioventricular septum repair, and valve replacement. The clinical demand for better cardiovascular patch materials is still urgent. However, the cardiovascular patch materials need to adapt to normal coagulation mechanism and durability, promote short-term endothelialization after surgery, and inhibit long-term postoperative intimal hyperplasia, its research and development process is relatively complicated. Understanding the characteristics of various cardiovascular patch materials and their application in cardiovascular surgeries is important for the selection of new clinical surgical materials and the development of cardiovascular patch materials.

Advances in Mechanotransduction Pathway of Macrophage / 医用生物力学

Mechanical stimulation in micro-environment ( such as matrix stiffness, surface topography, cyclical stretch) can be perceived by macrophages through receptors on cell membrane, transmitted to the nucleus along the adhesion protein molecular chain and cytoskeleton, and also converted into biochemical signal to stimulate gene transcription. Mechanical stimulation drives various biological functions in macrophages, such as adhesion, proliferation, migration, and polarization, thereby playing a corresponding role in disease progression and tissue regeneration. This study demonstrates the role of micro-environment mechanics in macrophages polarization and function, and elucidates the related mechanism of mechanotransduction pathway in macrophages, so as to provide molecular biomechanics insights into the development of macrophage-targeting immunomodulatorybiomaterials.

Progress in preparation and application of biomimetic nano carriers for cell membrane / 药学实践与服务

Nanocarriers prepared from organic or inorganic materials are widely used in drug targeting system and diagnosis and treatment of disease. However, there are some problems, such as poor targeting, short circulation time in vivo and improvement in the biocompatibility. Biomimetic nanocarriers has carried out research on the issues, which based on different kinds of cell membrane for the nanocarriers modification, endogenous biofilm improving the biocompatibility of carriers in vivo, more accurate targeting, and even producing immunotherapeutic effect. The principle, method, targeting mechanism and therapeutic effect of biomimetic nano carrier technology of cell membrane have been reviewed in this paper, which provide a new direction for the research of new drug delivery system.

Research Progress of Indole in E.coli Biofilms on the Surface of Biomaterials / 昆明医科大学学报

Escherichia coli is a highly adaptable opportunistic pathogen bacterium that can form biofilms on the surface of implants and generates persistent cells,leading to life-threatening infections that are difficult to treat with antibiotics alone.Therefore,there is a need for an effective E.coli biofilm inhibitor to combat this public health threat.Indole is a novel quorum-sensing signaling molecule of E.coli discovered in recent years,which is of great significance in regulating bacterial growth and biofilm formation,and is a potential target for future research on new anti-biofilm preparations.This article reviews the research progress on the formation of Escherichia coli biofilms,the microbial metabolism of indole and its regulation of Escherichia coli biofilm formation,in order to provide information for clinical treatment and drug development.

Advancing drug delivery to articular cartilage: From single to multiple strategies

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

The role of bacteria and its derived biomaterials in cancer radiotherapy

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

Advances in the raw material selection and functional design of artificial nerve guidance conduits / 生物工程学报

Artificial nerve guidance conduits (NGCs) are synthetic nerve grafts that are capable of providing the structural and nutritional support for nerve regeneration. The ideal NGCs have plenty of requirements on biocompatibility, mechanical strength, topological structure, and conductivity. Therefore, it is necessary to continuously improve the design of NGCs and establish a better therapeutic strategy for peripheral nerve injury in order to meet clinical needs. Although current NGCs have made certain process in the treatment of peripheral nerve injury, their nerve regeneration and functional outcomes on repairing long-distance nerve injury remain unsatisfactory. Herein, we review the nerve conduit design from four aspects, namely raw material selection, structural design, therapeutic factor loading and self-powered component integration. Moreover, we summarize the research progress of NGCs in the treatment of peripheral nerve injury, in order to facilitate the iterative updating and clinical transformation of NGCs.

Research progress in leveraging biomaterials for enhancing NK cell immunotherapy / 浙江大学学报·医学版

NK cell immunotherapy is a promising antitumor therapeutic modality after the development of T cell immunotherapy. Structural modification of NK cells with biomaterials may provide a precise, efficient, and low-cost strategy to enhance NK cell immunotherapy. The biomaterial modification of NK cells can be divided into two strategies: surface engineering with biomaterials and intracellular modification. The surface engineering strategies include hydrophobic interaction of lipids, receptor-ligand interaction between membrane proteins, covalent binding to amino acid residues, click reaction and electrostatic interaction. The intracellular modification strategies are based on manipulation by nanotechnology using membranous materials from various sources of NK cells (such as exosome, vesicle and cytomembranes). Finally, the biomaterials-based strategies regulate the recruitment, recognition and cytotoxicity of NK cells in the solid tumor site in situ to boost the activity of NK cells in the tumor. This article reviews the recent research progress in enhancing NK cell therapy based on biomaterial modification, to provide a reference for further researches on engineering NK cell therapy with biomaterials.

Wearable patches for transdermal drug delivery

Transdermal drug delivery systems (TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials, design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics. This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.

Culture of rat mesenchymal stem cells on PHBV-PCL scaffolds: analysis of conditioned culture medium by FT Raman spectroscopy / Cultivo de células-tronco mesenquimais de rato sobre arcabouços de PHBV-PCL: análise do meio de cultura condicionado por espectroscopia de FT-Raman

Mesenchymal stem cells (MSCs) have great potential for application in cell therapy and tissue engineering procedures because of their plasticity and capacity to differentiate into different cell types. Given the widespread use of MSCs, it is necessary to better understand some properties related to osteogenic differentiation, particularly those linked to biomaterials used in tissue engineering. The aim of this study was to develop an analysis method using FT-Raman spectroscopy for the identification and quantification of biochemical components present in conditioned culture media derived from MSCs with or without induction of osteogenic differentiation. All experiments were performed between passages 3 and 5. For this analysis, MSCs were cultured on scaffolds composed of bioresorbable poly(hydroxybutyrate co-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) polymers. MSCs (GIBCO®) were inoculated onto the pure polymers and 75:25 PHBV/PCL blend (dense and porous samples). The plate itself was used as control. The cells were maintained in DMEM (with low glucose) containing GlutaMAX® and 10% FBS at 37ºC with 5% CO2 for 21 days. The conditioned culture media were collected and analyzed to probe for functional groups, as well as possible molecular variations associated with cell differentiation and metabolism. The method permitted to identify functional groups of specific molecules in the conditioned medium such as cholesterol, phosphatidylinositol, triglycerides, beta-subunit polypeptides, amide regions and hydrogen bonds of proteins, in addition to DNA expression. In the present study, FT-Raman spectroscopy exhibited limited resolution since different molecules can express similar or even the same stretching vibrations, a fact that makes analysis difficult. There were no variations in the readings between the samples studied. In conclusion, FT-Raman spectroscopy did not meet expectations under the conditions studied.

As células-tronco mesenquimais (MSCs) possuem grande potencial para aplicação em procedimentos terapêuticos ligados a terapia celular e engenharia de tecidos, considerando-se a plasticidade e capacidade de formação em diferentes tipos celulares por elas. Dada a abrangência no emprego das MSCs, há necessidade de se compreender melhor algumas propriedades relacionadas à diferenciação osteogênica, particularmente liga à biomateriais usados em engenharia de tecidos. Este projeto objetiva o desenvolvimento de uma metodologia de análise empregando-se a FT-Raman para identificação e quantificação de componentes bioquímicos presentes em meios de cultura condicionados por MSCs, com ou sem indução à diferenciação osteogênica. Todos os experimentos foram realizados entre as passagens 3 e 5. Para essas análises, as MSCs foram cultivadas sobre arcabouços de polímeros biorreabsorvíveis de poli (hidroxibutirato-co-hidroxivalerato) (PHBV) e o poli (ε-caprolactona) (PCL). As MSCs (GIBCO®) foram inoculadas nos polímeros puros e na mistura 75:25 de PHBV / PCL (amostras densas e porosas). As células foram mantidas em DMEM (com baixa glicose) contendo GlutaMAX® e 10% de SFB a 37oC com 5% de CO2 por 21 dias. A própria placa foi usada como controle. Os meios de cultura condicionados foram coletados e analisadas em FT-Raman para sondagem de grupos funcionais, bem como possíveis variações moleculares associadas com a diferenciação e metabolismo celular. Foi possível discernir grupos funcionais de moléculas específicas no meio condicionado, como colesterol, fosfatidilinositol, triglicerídeos, forma Beta de polipeptídeos, regiões de amida e ligações de hidrogênio de proteínas, além da expressão de DNA. Na presente avaliação, a FT-Raman apresentou como uma técnica de resolução limitada, uma vez que modos vibracionais de estiramento próximos ou mesmo iguais podem ser expressos por moléculas diferente, dificultando a [...].

Culture of rat mesenchymal stem cells on PHBV-PCL scaffolds: analysis of conditioned culture medium by FT-Raman spectroscopy

Abstract Mesenchymal stem cells (MSCs) have great potential for application in cell therapy and tissue engineering procedures because of their plasticity and capacity to differentiate into different cell types. Given the widespread use of MSCs, it is necessary to better understand some properties related to osteogenic differentiation, particularly those linked to biomaterials used in tissue engineering. The aim of this study was to develop an analysis method using FT-Raman spectroscopy for the identification and quantification of biochemical components present in conditioned culture media derived from MSCs with or without induction of osteogenic differentiation. All experiments were performed between passages 3 and 5. For this analysis, MSCs were cultured on scaffolds composed of bioresorbable poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(-caprolactone) (PCL) polymers. MSCs (GIBCO®) were inoculated onto the pure polymers and 75:25 PHBV/PCL blend (dense and porous samples). The plate itself was used as control. The cells were maintained in DMEM (with low glucose) containing GlutaMAX® and 10% FBS at 37oC with 5% CO2 for 21 days. The conditioned culture media were collected and analyzed to probe for functional groups, as well as possible molecular variations associated with cell differentiation and metabolism. The method permitted to identify functional groups of specific molecules in the conditioned medium such as cholesterol, phosphatidylinositol, triglycerides, beta-subunit polypeptides, amide regions and hydrogen bonds of proteins, in addition to DNA expression. In the present study, FT-Raman spectroscopy exhibited limited resolution since different molecules can express similar or even the same stretching vibrations, a fact that makes analysis difficult. There were no variations in the readings between the samples studied. In conclusion, FT-Raman spectroscopy did not meet expectations under the conditions studied.

Resumo As células-tronco mesenquimais (MSCs) possuem grande potencial para aplicação em procedimentos terapêuticos ligados a terapia celular e engenharia de tecidos, considerando-se a plasticidade e capacidade de formação em diferentes tipos celulares por elas. Dada a abrangência no emprego das MSCs, há necessidade de se compreender melhor algumas propriedades relacionadas à diferenciação osteogênica, particularmente liga à biomateriais usados em engenharia de tecidos. Este projeto objetiva o desenvolvimento de uma metodologia de análise empregando-se a FT-Raman para identificação e quantificação de componentes bioquímicos presentes em meios de cultura condicionados por MSCs, com ou sem indução à diferenciação osteogênica. Todos os experimentos foram realizados entre as passagens 3 e 5. Para essas análises, as MSCs foram cultivadas sobre arcabouços de polímeros biorreabsorvíveis de poli (hidroxibutirato-co-hidroxivalerato) (PHBV) e o poli (-caprolactona) (PCL). As MSCs (GIBCO®) foram inoculadas nos polímeros puros e na mistura 75:25 de PHBV / PCL (amostras densas e porosas). As células foram mantidas em DMEM (com baixa glicose) contendo GlutaMAX® e 10% de SFB a 37oC com 5% de CO2 por 21 dias. A própria placa foi usada como controle. Os meios de cultura condicionados foram coletados e analisadas em FT-Raman para sondagem de grupos funcionais, bem como possíveis variações moleculares associadas com a diferenciação e metabolismo celular. Foi possível discernir grupos funcionais de moléculas específicas no meio condicionado, como colesterol, fosfatidilinositol, triglicerídeos, forma Beta de polipeptídeos, regiões de amida e ligações de hidrogênio de proteínas, além da expressão de DNA. Na presente avaliação, a FT-Raman apresentou como uma técnica de resolução limitada, uma vez que modos vibracionais de estiramento próximos ou mesmo iguais podem ser expressos por moléculas diferente, dificultando a análise. Não houve variações nas leituras entre as amostras estudadas, concluindo-se que a FT-Raman não atendeu às expectativas nas condições estudadas.