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Browsing by Author "Bordini, Ester A. F."
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Item Engineering of Injectable Antibiotic-laden Fibrous Microparticles Gelatin Methacryloyl Hydrogel for Endodontic Infection Ablation(MDPI, 2022-01-16) Ribeiro, Juliana S.; Münchow, Eliseu A.; Bordini, Ester A. F.; Rodrigues, Nathalie S.; Dubey, Nileshkumar; Sasaki, Hajime; Fenno, John C.; Schwendeman, Steven; Bottino, Marco C.; Biomedical and Applied Sciences, School of DentistryThis study aimed at engineering cytocompatible and injectable antibiotic-laden fibrous microparticles gelatin methacryloyl (GelMA) hydrogels for endodontic infection ablation. Clindamycin (CLIN) or metronidazole (MET) was added to a polymer solution and electrospun into fibrous mats, which were processed via cryomilling to obtain CLIN- or MET-laden fibrous microparticles. Then, GelMA was modified with CLIN- or MET-laden microparticles or by using equal amounts of each set of fibrous microparticles. Morphological characterization of electrospun fibers and cryomilled particles was performed via scanning electron microscopy (SEM). The experimental hydrogels were further examined for swelling, degradation, and toxicity to dental stem cells, as well as antimicrobial action against endodontic pathogens (agar diffusion) and biofilm inhibition, evaluated both quantitatively (CFU/mL) and qualitatively via confocal laser scanning microscopy (CLSM) and SEM. Data were analyzed using ANOVA and Tukey's test (α = 0.05). The modification of GelMA with antibiotic-laden fibrous microparticles increased the hydrogel swelling ratio and degradation rate. Cell viability was slightly reduced, although without any significant toxicity (cell viability > 50%). All hydrogels containing antibiotic-laden fibrous microparticles displayed antibiofilm effects, with the dentin substrate showing nearly complete elimination of viable bacteria. Altogether, our findings suggest that the engineered injectable antibiotic-laden fibrous microparticles hydrogels hold clinical prospects for endodontic infection ablation.Item Metformin-Loaded Nanospheres Laden Photocrosslinkable Gelatin Hydrogel for Bone Tissue Engineering(Elsevier, 2021) Qu, Liu; Dubey, Nileshkumar; Ribeiro, Juliana S.; Bordini, Ester A. F.; Ferreira, Jessica A.; Xu, Jinping; Castilho, Rogerio M.; Bottino, Marco C.; Biomedical and Applied Sciences, School of DentistryThe aim of this investigation was to engineer metformin (MF)-loaded mesoporous silica nanospheres (MSNs)-laden gelatin methacryloyl (GelMA) photocrosslinkable hydrogels and test their effects on the mechanical properties, swelling ratio, drug release, cytocompatibility, and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). As-received and carboxylated MSNs (MSNs-COOH) were characterized by scanning and transmission electron microscopies (SEM and TEM), as well as Fourier-transform infrared spectroscopy (FTIR) prior to hydrogel modification. MF-MSNs-COOH were obtained by loading MF into MSNs at a 1:1 mass ratio. Upon MSNs-COOH laden-hydrogels fabrication, the mechanical properties, swelling ratio and MF release were evaluated. SHEDs were seeded on the hydrogels and cytocompatibility was examined. The effects of the MF-MSNs-COOH/GelMA on the osteogenic differentiation of SHEDs were measured by ALP activity, Alizarin Red assay, and Real-time PCR. Statistics were performed using one-way ANOVA (α = 0.05). Morphological (SEM and TEM) analyses of pristine and carboxylated MSNs revealed a mean particle size of 200 nm and 218 nm, respectively. Importantly, an intrinsic nanoporous structure was noticed. Incorporation of MSNs-COOH at 1.5 mg/mL in GelMA led to the highest compressive modulus and swelling ratio. The addition of MSNs-COOH (up to 3 mg/mL) in GelMA did not impact cell viability. The presence of MF in MSNs-COOH/GelMA significantly promoted cell proliferation. Significant upregulation of osteogenic-related genes (except OCN) were seen for modified (MSNs-COOH and MF-MSNs-COOH) hydrogels when compared to GelMA. Altogether, the engineered MF-MSNs-COOH/GelMA shows great promise in craniomaxillofacial applications as an injectable, cell-free and bioactive therapeutics for bone regeneration.Item Platform Technologies for Regenerative Endodontics from Multifunctional Biomaterials to Tooth-on-a-Chip Strategies(Springer, 2021) Soares, Diana G.; Bordini, Ester A. F.; Swanson, W. Benton; de Souza Costa, Carlos A.; Bottino, Marco C.; Biomedical and Applied Sciences, School of DentistryObjectives: The aim of this review is to highlight recent progress in the field of biomaterials-mediated dental pulp tissue engineering. Specifically, we aim to underscore the critical design criteria of biomaterial platforms that are advantageous for pulp tissue engineering, discuss models for preclinical evaluation, and present new and innovative multifunctional strategies that hold promise for clinical translation. Materials and methods: The current article is a comprehensive overview of recent progress over the last 5 years. In detail, we surveyed the literature in regenerative pulp biology, including novel biologic and biomaterials approaches, and those that combined multiple strategies, towards more clinically relevant models. PubMed searches were performed using the keywords: "regenerative dentistry," "dental pulp regeneration," "regenerative endodontics," and "dental pulp therapy." Results: Significant contributions to the field of regenerative dentistry have been made in the last 5 years, as evidenced by a significant body of publications. We chose exemplary studies that we believe are progressive towards clinically translatable solutions. We close this review with an outlook towards the future of pulp regeneration strategies and their clinical translation. Conclusions: Current clinical treatments lack functional and predictable pulp regeneration and are more focused on the treatment of the consequences of pulp exposure, rather than the restoration of healthy dental pulp. Clinical relevance: Clinically, there is great demand for bioinspired biomaterial strategies that are safe, efficacious, and easy to use, and clinicians are eager for their clinical translation. In particular, we place emphasis on strategies that combine favorable angiogenesis, mineralization, and functional tissue formation, while limiting immune reaction, risk of microbial infection, and pulp necrosis.