Browsing by Subject "Scaffolds"

Now showing 1 - 7 of 7
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    A Highly Ordered, Nanostructured Fluorinated CaP-Coated Melt Electrowritten Scaffold for Periodontal Tissue Regeneration
    (Wiley, 2021) Daghrery, Arwa; Ferreira, Jessica A.; de Souza Araújo, Isaac J.; Clarkson, Brian H.; Eckert, George J.; Bhaduri, Sarit B.; Malda, Jos; Bottino, Marco C.; Biostatistics, School of Public Health
    Periodontitis is a chronic inflammatory, bacteria-triggered disorder affecting nearly half of American adults. Although some level of tissue regeneration is realized, its low success in complex cases demands superior strategies to amplify regenerative capacity. Herein, highly ordered scaffolds are engineered via Melt ElectroWriting (MEW), and the effects of strand spacing, as well as the presence of a nanostructured fluorinated calcium phosphate (F/CaP) coating on the adhesion/proliferation, and osteogenic differentiation of human-derived periodontal ligament stem cells, are investigated. Upon initial cell-scaffold interaction screening aimed at defining the most suitable design, MEW poly(𝝐-caprolactone) scaffolds with 500 µm strand spacing are chosen. Following an alkali treatment, scaffolds are immersed in a pre-established solution to allow for coating formation. The presence of a nanostructured F/CaP coating leads to a marked upregulation of osteogenic genes and attenuated bacterial growth. In vivo findings confirm that the F/CaP-coated scaffolds are biocompatible and lead to periodontal regeneration when implanted in a rat mandibular periodontal fenestration defect model. In aggregate, it is considered that this work can contribute to the development of personalized scaffolds capable of enabling tissue-specific differentiation of progenitor cells, and thus guide simultaneous and coordinated regeneration of soft and hard periodontal tissues, while providing antimicrobial protection.
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    Advanced biomaterials for periodontal tissue regeneration
    (Wiley, 2022) Daghrery, Arwa; Bottino, Marco C.; Biomedical and Applied Sciences, School of Dentistry
    The periodontium is a suitable target for regenerative intervention, since it does not functionally restore itself after disease. Importantly, the limited regeneration capacity of the periodontium could be improved with the development of novel biomaterials and therapeutic strategies. Of note, the regenerative potential of the periodontium depends not only on its tissue‐specific architecture and function, but also on its ability to reconstruct distinct tissues and tissue interfaces, suggesting that the advancement of tissue engineering approaches can ultimately offer new perspectives to promote the organized reconstruction of soft and hard periodontal tissues. Here, we discuss material‐based, biologically active cues, and the application of innovative biofabrication technologies to regenerate the multiple tissues that comprise the periodontium.
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    Advanced Scaffolds for Dental Pulp and Periodontal Regeneration
    (Elsevier, 2017-10) Bottino, Marco C.; Pankajakshan, Divya; Nör, Jacques E.; Biomedical Sciences and Comprehensive Care, School of Dentistry
    No current therapy promotes root canal disinfection and regeneration of the pulp-dentin complex in cases of pulp necrosis. Antibiotic pastes used to eradicate canal infection negatively affect stem cell survival. Three-dimensional easy-to-fit antibiotic-eluting nanofibers, combined with injectable scaffolds, enriched or not with stem cells and/or growth factors, may increase the likelihood of achieving predictable dental pulp regeneration. Periodontitis is an aggressive disease that impairs the integrity of tooth-supporting structures and may lead to tooth loss. The latest advances in membrane biomodification to endow needed functionalities and technologies to engineer patient-specific membranes/constructs to amplify periodontal regeneration are presented.
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    Effects of ciprofloxacin-containing antimicrobial scaffolds on dental pulp stem cell viability-In vitro studies
    (Elsevier, 2015-08) Kamocki, Krzysztof; Nör, Jacques E.; Bottino, Marco C.; Department of Restorative Dentistry, School of Dentistry
    OBJECTIVE: A combination of antibiotics, including but not limited to metronidazole (MET) and ciprofloxacin (CIP), has been indicated to eradicate bacteria in necrotic immature permanent teeth prior to regenerative procedures. It has been shown clinically that antibiotic pastes may lead to substantial stem cell death. The aim of this study was to synthesise scaffolds containing various concentrations of CIP to enhance cell viability while preserving antimicrobial properties. DESIGN: Polydioxanone (PDS)-based electrospun scaffolds were processed with decreasing CIP concentrations (25-1 wt.%) and morphologically evaluated using scanning electron microscopy (SEM). Cytotoxicity assays were performed to determine whether the amount of CIP released from the scaffolds would lead to human dental pulp stem cell (hDPSC) toxicity. Similarly, WST-1 assays were performed to evaluate the impact of CIP release on hDPSC proliferation. Pure PDS scaffolds and saturated double antibiotic solution MET/CIP (DAP) served as both positive and negative controls, respectively. Antibacterial efficacy against E. faecalis (Ef) was tested. RESULTS: A significant decrease in hDPSC' viability at concentrations 5-25 wt.% was observed. However, concentrations below 5wt.% did not impair cell viability. Data from the WST-1 assays indicated no detrimental impact on cell proliferation for scaffolds containing 2.5 wt.% CIP or less. Significant antimicrobial properties were seen for CIP-scaffolds at lower concentrations (i.e., 1 and 2.5 wt.%). CONCLUSION: The obtained data demonstrated that a reduced concentration of CIP incorporated into PDS-based scaffolds maintains its antimicrobial properties while enhancing viability and proliferation of dental pulp stem cells.
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    Photocrosslinkable methacrylated gelatin hydrogel as a cell-friendly injectable delivery system for chlorhexidine in regenerative endodontics
    (Elsevier, 2022) Ribeiro, Juliana S.; Sanz, Carolina K.; Münchow, Eliseu A.; Kalra, Nikhil; Dubey, Nileshkumar; Suárez, Carlos Enrique C.; Fenno, J. Christopher; Lund, Rafael G.; Bottino, Marco C.; Biomedical and Applied Sciences, School of Dentistry
    Objectives: This work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures. Methods: CHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels' biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey's test (α = 0.05). Results: CHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %. Significance: The addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.
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    Self-assembling peptide-laden electrospun scaffolds for guided mineralized tissue regeneration
    (Elsevier, 2022) de Souza Araújo, Isaac J.; Ferreira, Jessica A.; Daghrery, Arwa; Ribeiro, Juliana S.; Castilho, Miguel; Puppin-Rontani, Regina M.; Bottino, Marco C.; Biomedical and Applied Sciences, School of Dentistry
    Objectives: Electrospun scaffolds are a versatile biomaterial platform to mimic fibrillar structure of native tissues extracellular matrix, and facilitate the incorporation of biomolecules for regenerative therapies. Self-assembling peptide P11-4 has emerged as a promising strategy to induce mineralization; however, P11-4 application has been mostly addressed for early caries lesions repair on dental enamel. Here, to investigate P11-4's efficacy on bone regeneration, polymeric electrospun scaffolds were developed, and then distinct concentrations of P11-4 were physically adsorbed on the scaffolds. Methods: P11-4-laden and pristine (P11-4-free) electrospun scaffolds were immersed in simulated body fluid and mineral precipitation identified by SEM. Functional groups and crystalline phases were analyzed by FTIR and XRD, respectively. Cytocompatibility, mineralization, and gene expression assays were conducted using stem cells from human exfoliated deciduous teeth. To investigate P11-4-laden scaffolds potential to induce in vivo mineralization, an established rat calvaria critical-size defect model was used. Results: We successfully synthesized nanofibrous (∼ 500 nm fiber diameter) scaffolds and observed that functionalization with P11-4 did not affect the fibers' diameter. SEM images indicated mineral precipitation, while FTIR and XRD confirmed apatite-like formation and crystallization for P11-4-laden scaffolds. In addition, P11-4-laden scaffolds were cytocompatible, highly stimulated cell-mediated mineral deposition, and upregulated the expression of mineralization-related genes compared to pristine scaffolds. P11-4-laden scaffolds led to enhanced in vivo bone regeneration after 8 weeks compared to pristine PCL. Significance: Electrospun scaffolds functionalized with P11-4 are a promising strategy for inducing mineralized tissues regeneration in the craniomaxillofacial complex.
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    Three-Dimensional Printing of Clinical Scale and Personalized Calcium Phosphate Scaffolds for Alveolar Bone Reconstruction
    (Elsevier, 2022) Anderson, Margaret; Dubey, Nileshkumar; Bogie, Kath; Cao, Chen; Li, Junying; Lerchbacker, Joseph; Mendonça, Gustavo; Kauffman, Frederic; Bottino, Marco C.; Kaigler, Darnell; Biomedical and Applied Sciences, School of Dentistry
    Objective: Alveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. Methods: Two types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/β-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use cone beam computed tomographic (CBCT) imaging to design and 3D print, defect-specific bioceramic scaffolds for clinical-scale bone defects. Results: Osteoink™ scaffolds had the highest compressive strength when compared to hybrid CaP with different infill orientation. In cell culture medium, hybrid CaP degradation resulted in decreased pH (6.3) and toxicity to stem cells; however, OsteoInk™ scaffolds maintained a stable pH (7.2) in culture and passed the ISO standard for cytotoxicity. Finally, a clinically feasible laboratory workflow was developed and evaluated using CBCT imaging to engineer customized and defect-specific CaP scaffolds using OsteoInk™. It was determined that printed scaffolds had a high degree of accuracy to fit the respective clinical defects for which they were designed (0.27 mm morphological deviation of printed scaffolds from digital design). Significance: From patient to patient, large alveolar bone defects are difficult to treat due to high variability in their complex morphologies and architecture. Our findings shows that Osteoink™ is a biocompatible material for 3D printing of clinically acceptable, patient-specific scaffolds with precision-fit for use in alveolar bone reconstructive procedures. Collectively, emerging digital technologies including CBCT imaging, 3D surgical planning, and (bio)printing can be integrated to address this unmet clinical challenge.