MONICA BEATRIZ MATHOR

Resumo

Possui graduação em Farmácia e Bioquímica - modalidade Análises Clínicas e Toxicológicas pela Faculdade de Ciências Farmacêuticas (1979), mestrado em Tecnologia Nuclear pela Universidade de São Paulo (1983) e doutorado em Tecnologia Nuclear Básica pelo Instituto de Pesquisas Energéticas e Nucleares (1995). Atualmente é orientadora de cursos de pós-graduação da Universidade de São Paulo e pesquisador do Instituto de Pesquisas Energéticas e Nucleares. Foi gerente do Centro de Biotecnologia (1999-2001) e gerente adjunto de Pesquisa, Desenvolvimento & Inovação do centro de tecnologia das radiações (2013-2018). Tem experiência na área de Morfologia, com ênfase em Citologia e Biologia Celular, atuando principalmente nos seguintes temas: bancos de tecidos, efeitos da radiação ionizante em tecidos biológicos, inativação viral por radiação ionizante, cultura celular, queratinócitos, melanócitos, fibroblastos, Langerhans, ADSCs, substitutos dermo-epidérmicos, skin-on-a-chip e engenharia tecidual. (Texto extraído do Currículo Lattes em 18 nov. 2021)

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  • Artigo IPEN-doc 30372
    Use of collagen and auricular cartilage in bioengineering
    2024 - MASSIMINO, LIVIA C.; MARTINS, VIRGINIA da C.A.; VULCANI, VALCINIR A.S.; OLIVEIRA, EVERTON L. de; ANDREETA, MARIANE B.; BONAGAMBA, TITO J.; KLINGBEIL, MARIA F.G.; MATHOR, MONICA B.; PLEPIS, ANA M. de G.
    The aim of this study was the development of collagen and collagen/auricular cartilage scaffolds for application in dermal regeneration. Collagen was obtained from bovine tendon by a 72 h-long treatment, while bovine auricular cartilage was treated for 24 h and divided into two parts, external (perichondrium, E) and internal (elastic cartilage, I). The scaffolds were prepared by mixing collagen (C) with the internal part (CI) or the external part (CE) in a 3:1 ratio. Differential scanning calorimetry, scanning electron microscopy (SEM) analysis, microcomputed tomography imaging (micro-CT) and swelling degree were used to characterize the scaffolds. Cytotoxicity, cell adhesion, and cell proliferation assays were performed using the cell line NIH/3T3. All samples presented a similar denaturation temperature (Td) around 48 degrees C, while CE presented a second Td at 51.2 degrees C. SEM micrographs showed superficial pores in all scaffolds and micro-CT exhibited interconnected pore spaces with porosity above 60% (sizes between 47 and 149 mu m). The order of swelling was CE < CI < C and the scaffolds did not present cytotoxicity, showing attachment rates above 75%-all samples showed a similar pattern of proliferation until 168 h, whereas CI tended to decrease after this time. The scaffolds were easily obtained, biocompatible and had adequate morphology for cell growth. All samples showed high adhesion, whereas collagen-only and collagen/external part scaffolds presented a better cell proliferation rate and would be indicated for possible use in dermal regeneration.
  • Resumo IPEN-doc 30284
    Development of chitosan containing vegetable oil scaffolds by 3D printing aiming chronic epithelial wound repair
    2023 - SANTOS, PAULA L. dos; LOURENCO, LARISSA; MATHOR, MONICA B.; MARCHI, JULIANA
    Introduction and objective: Wound healing can be disrupted, slowing down the healing process and thus resulting in chronic wounds. In the context of skin repair, chitosan is a promising natural polymer, with antimicrobial and antioxidant properties. Such materials can form hydrogels, being suitable for 3D printing process. Vegetable oils are in general composed of essential fatty acids, vitamins, and minerals that can contribute to wound healing. In this work scaffolds based on chitosan incorporated with different concentrations of vegetable oil were produced by 3D printing, aiming at the healing of chronic epithelial wounds. Methodology Hydrogels were produced by varying the vegetable oil percentage in the chitosan matrix. They were used as ink for 3D printing aiming the production of scaffolds. The mechanical properties of these structures were studied through tensile behaviour of wet and dry scaffolds. Indirect cytotoxicity, adhesion, and proliferation assays up to 96hs were carried out using balb/c 3T3 cells to explore the biological properties of the material. Results and discussion The printed scaffolds presented good shape fidelity when compared to the CAD models and displayed better results with the vegetable oil incorporation in the chitosan hydrogel. The tensile experiments showed that the dried scaffolds have higher mechanical properties and behave as soft materials in wet conditions. The in vitro toxicity assay results showed that the degradation products of the scaffolds were non-toxic, and increased cell viability in a dose/dependent manner. Vegetable oil increased cell adhesion of the chitosan scaffold, with better results at lower oil concentrations. The proliferation assay showed better results for chitonsan containing vegetable oil in early stages. However, for 96hs, pure chitosan have better cell proliferation. Conclusions: Scaffolds of chitosan containing vegetable oil have potential applications as wound dressings, acting in physical and microbiological protection and cell proliferation of the tissue. Other biological assays are indicated to confirm the possibility of applying these biomaterials in chronic wounds.
  • Resumo IPEN-doc 30283
    Chitosan hydrogel containing bioactive glass aiming at 3D printing for peripheralnerve regeneration
    2023 - LOURENÇO, LARISSA; BORGES, ROGER; CARASTAN, DANILO; SILVA, CASTRO; MATHOR, MONICA B.; MARCHI, JULIANA
    Introduction and objective: Peripheral nerve lesions are a challenge in the context of regeneration. Tissue engineering strategy can increase repair success using biomaterials and cells. Chitosan is a biocompatible natural polymer, with good cost-effectiveness and rheological properties that has been shown to be suitable for nerve regeneration. Bioactive glasses exhibited the ability to increase the production of neurotrophicsubstances in in vivo experiments that could assist nerve repair. 3D printing presents the possibility of building complex and patient-specific structures. Thus, the development of chitosan hydrogels with different concentrations of bioactive glasses for 3D printing is proposed for future application in peripheral nerveregeneration. Methodology: Chitosan hydrogel was produced with different concentrations of bioactive glass (0, 0.5%, 1%, 2%, and 5%). The rheological characterization of the hydrogels was carried out by shear sweep and creep- recovery experiments. Printability and shape fidelity were evaluated after the 3D printing process through the comparison of the theoretical CAD model and printed structure. Indirect cytotoxicity assay using PC12 cells wasperformed to evaluate the biological properties of the scaffolds. Results and discussion: The presence of glass affects the rheological properties of chitosan hydrogel. The shear sweep results showed that the viscosity of the chitosan containing bioactive glass decreases at the lowest shearrate compared to pure chitosan hydrogel. However, the viscosity of hydrogels containing higher concentrations of glass (2% and 5%) increases when compared to the other composites. Such behaviour is a consequence of two events: the presence of the bioactive glass particles and the ions release, caused by glass dissolution in the material, which can interact with the polymeric chains and disrupt the formation of intermolecular interactions. Furthermore, the incorporation of the ceramic particles increased the recovery percentage of the material. This raise is caused by the interactions between the bioactive glass surface and chitosan chains, increasing the hydrogel’s stability. These rheological characteristics improved shape fidelity of the material and possible use as ink for 3D printing. Biologically, the extracts of the materials had a non-toxic effect on the PC12 cells. Conclusions: The presence of glass affects the rheological properties of chitosan hydrogel to improve its use as 3D printing ink. The biological experiments showed that the materials do not have cytotoxic effects and could be used in tissue engineering. Therefore, chitosan hydrogel with bioactive glass particles are promising materials for application in peripheral nerve regeneration.
  • Resumo IPEN-doc 30280
    Determination of radioresistance of contaminant bacteria in nile tilapia skin used as a dressing
    2023 - BARNA, FERNANDA S.; BANDEIRA, TEREZA J.P.G.; PAIER, CARLOS R.K.; RODRIGUES, FELIPE A.R.; LIMA JUNIOR, EDMAR M.; MARAES FILHO, MANUEL O. de; MATHOR, MONICA B.
    Introduction and objective: The use of Nile Tilapia (Oreochromis niloticus) skin in regenerative medicine, in the form of biological dressing for burns, is satisfactory because this biomaterial presents good adherence to wounds and characteristics suitable for the healing process, such as the high concentration of collagen type I. The treatment with the skin provides protection and decreases the number of dressing changes, reducing the patient's pain. Before use, Nile Tilapia skins need to be decontaminated and sterilized ensuring safety, since they can be contaminated by bacteria during handling. Each bacterium has a radioresistance value, which inactivates 90% of the population of that species. Methodology: Some human contaminations at the time of handling this material: Enterococcus faecalis, Pseudomonas aeruginosa and Pseudomonas putida. In this work we irradiated the isolated bacterial populations from the Nile Tilapia skin with increasing doses of ionizing radiation in culture medium. Serial dilutions were performed from the total population, after gamma-ray irradiation, to enable the identification of the remaining bacterial concentration for each dose of irradiation tested. Results and discussion: In the literature it is possible to find radioresistance to these bacteria contained in other substrates. However, it is necessary to standardize the methodology to determine the radioresistance of microbial species in the skin of Nile Tilapia, to ensure patient safety during the use of the dressing. For Enterococcus faecalis we obtained a value of 0.7 kGy, very similar to that described in the literature. For Pseudomonas aeruginosa the value found was 0.5 kGy and for Pseudomonas putida it was 0.2 kGy. Thus, the standardization of the methodology is in accordance with normality, also allowing the determination of radioresistance for some bacteria not described in the literature. Conclusions: It was possible to estimate the values of the doses necessary for the reduction of 90% of the bacterial population. The radiation doses were standardized to sterilize with a safety level of 10-6, but without reaching values harmful to the histological and molecular structure of the biomaterial (above 25 kGy), so that the biological dressing is used in patients safely and doesn’t lose its physicochemical characteristics.
  • Resumo IPEN-doc 30279
    Development of human fibroblast spheroids with hanging-drop inverted plates
    2023 - RODRIGUES, ALEX A.; SAMPAIO, MARLOS C.; SANTOS, ESTHER C. dos; PRUDENTE, SULEYNA R.; LIMA, MAYELLE M.P.; SILVA, GIOVANA D. da; MATHOR, MONICA B.; VIEIRA, DANIEL P.
    Introduction and objective: 2D cultures have limitations in cell growth. 3D cultures, on the other hand, have become a valuable and powerful tool for biomedical research in recent decades. Due to their resemblance to living systems and cellular interactions, this type of culture can be developed using various methodologies, including nanoparticles, hydrogels, and layers of agarose, among others. Considering the need for testing and validating new molecules and effective therapies for treating various diseases, the objective of this study is to standardize a 3D human fibroblast culture model. Methodology: HF002-J, human fibroblast cells, were cultured at 37ºC in a humid atmosphere containing 5% CO2, maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% antibiotics. When reaching 60- 70% confluence, the cells were detached using a 0.05% trypsin solution. Spheroids were prepared using the hangingdrop technique adapted from [1] 440 µL of medium containing cell variations ranging from 2 × 103 to 6 × 104 cells per well of a 96-well plate were deposited, generating a positive meniscus. The plate was inverted and incubated as described. Results and discussion: The present study aimed to evaluate the development of cellular spheroids after 4 days of culture using different cell preparations. Our results demonstrated that the preparations used produced compact spheroids, characterized by homogeneous sizes in the range of 500 to 1000 μm. When analysing the images obtained by wide-field fluorescence microscopy, we observed that the proportions of unviable cells labelled with fluorophores varied significantly according to the initial number of cells used in the preparations. Notably, increasing the initial number of cells resulted in a proportional increase in the number of non-viable cells present in the formed spheroids. These results suggest that the initial cell density can affect the development and viability of the formed spheroids. It is possible that too high cell density led to greater competition for nutrients and space, resulting in greater cell mortality and less viable spheroids. Conclusions: Based on the results obtained, it was possible to develop an initial prototype of spheroids from human fibroblast cells that can resemble tissues in vivo due to their cellular interactions, thus providing a new tool for the study of drugs and treatments.
  • Resumo IPEN-doc 30155
    Chitosan hydrogel containing bioactive glass aiming at 3D printing for tissue engineering
    2023 - LOURENCO, LARISSA R.; BORGES, ROGER; CARASTAN, DANILO J.; MATHOR, MONICA B.; MARCHI, JULIANA
    3D printing is a rising processing technique in tissue engineering due to high reproducibility and the possibility of complex or even patient-specific models. Chitosan is a promising biomaterial for both 3D printing and tissue engineering, because of its biocompatibility, rheological properties, biodegradability, and cost-effectiveness. Bioactive glasses can help the regeneration of different biological tissues and act as reinforcement for chitosan matrix. In this work, chitosan hydrogels were produced with different concentrations of 58S bioactive glass (0.5 up to 5%wt). For the rheological characterization, frequency, and recovery experiments were carried out. Printability and shape fidelity were evaluated during the 3D printing process. Indirect cytotoxicity assay using Balb/c 3T3 cells was performed to evaluate the biological properties of the scaffolds. The presence of the glass maintained the viscosity properties and increased the recovery percentage. All materials formed filaments and allowed printing with suitable form maintenance. Biological experiments showed high cell viability for all 3D scaffolds, even though a reduction was observed for higher glass concentrations. The results indicate that the studied materials are printable and potentially recommended for tissue engineering applications.
  • Artigo IPEN-doc 29713
    Physical, chemical, and biological characterization of biodegradable chitosan dressing for biomedical applications
    2023 - ERNESTO, JULIA V.; GASPARINI, ISIS de M.; CORAZZA, FULVIO G.; MATHOR, MONICA B.; SILVA, CLASSIUS F. da; LEITE-SILVA, VANIA R.; ANDREO-FILHO, NEWTON; LOPES, PATRICIA S.
    Chitosan, a biomaterial with properties that allows the elaboration of biocompatible and biodegradable systems, was employed to prepare dressings - 2% (w/v) in acetic acid - followed by freezing and lyophilization. Some samples were kept chemically unchanged and used as control, while others were cross-linked with Epichlorohydrin 0.01 mol L− 1 for 24 h being washed, frozen and lyophilized. The neutralization procedure was performed with sodium bicarbonate, which ended up leading to a crosslinking by ionic interactions in the polymer network, and characteristics as promising as those of the chemically cross-linked with Epichlorohydrin. SEM showed that the crosslinking leads to a controlled formation of the polymeric network, conferring suitable steam permeation capacity 107 g mm.day− 1 .m− 2 .kPa− 1 , simulated fluid permeation between 2000 and 2500 g m− 2 .day-1 and porosity with interconnection which allows fluid absorption capacity above 900%. The crosslinking processes favored a better handling mechanical resistance confirmed by biodegradation assays. The dressing blocked micro-organisms permeation, forming an efficient barrier against contamination, is safe and biocompatible, allowing satisfactory cell adhesion and proliferation. These results showed that both dressings present statistically and satisfactory equivalent characteristics to be used as a functional bio dressing suitable for the treatment of different pathologies.
  • Artigo IPEN-doc 29608
    Aloe vera and copaiba oleoresin-loaded chitosan films for wound dressings
    2023 - GENESI, BIANCA P.; BARBOSA, RAQUEL de M.; SEVERINO, PATRICIA; RODAS, ANDREA C.D.; YOSHIDA, CRISTIANA M.P.; MATHOR, MONICA B.; LOPES, PATRICIA S.; VISERAS, CESAR; SOUTO, ELIANA B.; SILVA, CLASSIUS F. da
    Chitosan films are commonly used for wound dressing, provided that this polymer has healing, mucoadhesiveness and antimicrobial properties. These properties can be further reinforced by the combination of chitosan with polysaccharides and glycoproteins present in aloe vera, together with copaiba oleoresin’s pharmacological activity attributed to sesquiterpenes. In this work, we developed chitosan films containing either aloe vera, copaiba oil or both, by casting technique, and evaluated their microbial permeation, antimicrobial activity, cytotoxicity, and in vivo healing potential in female adult rats. None of the developed chitosan films promoted microbial permeation, while the cytotoxicity in Balb/c 3 T3 clone A31 cell line revealed no toxicity of films produced with 2 % of chitosan and up to 1 % of aloe vera and copaiba oleoresin. Films obtained with either 0.5 % chitosan or 0.5 % copaiba oleoresin induced cell proliferation which anticipate their potential for closure of wound and for the healing process. The in vivo results confirmed that tested films (0.5 % copaiba-loaded chitosan film and 0.5 % aloe vera-loaded chitosan film) were superior to a commercial dressing film. For all tested groups, a fully formed epithelium was seen, while neoformation of vessels seemed to be greater in formulations-treated groups than those treated with the control. Our work confirms the added value of combining chitosan with aloe vera and copaiba oil in the healing process of wounds.
  • Resumo IPEN-doc 29448
    A biological study of gelatin-PVA based scaffold functionalized with albumin for biomedical purposes
    2022 - VARCA, J.O.; KLINGBEIL, F.; NOGUEIRA, K.M.; LIMA, C.S.; CRUZ, C.C. da; FREITAS, L.F.; VARCA, G.H.; MATHOR, M.B.; LUGAO, A.B.
    Biomaterials have been designed for tissue reconstruction, bone regeneration and cell culture, and functionalized with presence of proteins, nanoparticles, peptides and other components to improve the biocompatibility for instance. This work shows a biological study of gelatin-PVA based scaffold with controlled pore size and functionalized with albumin for biomedical purposes. The in vitro study comprises cytotoxicity, cell adhesion and proliferation assessment. In practical terms, the gelatin-PVA scaffold crosslinked and sterilized by gamma radiation followed by freeze-drying was evaluated by cytotoxicity, adhesion and proliferation tests. The cytotoxicity results showed that the biomaterial produced was non-toxic, and adhesion and proliferation assays showed that the material was suitable for tissue engineering. The presence of albumin did not present a significant impact on the cell performance, at the assayed concentration.