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Periodontitis compromises the integrity and function of tooth-supporting structures. Although therapeutic approaches have been offered, predictable regeneration of periodontal tissues remains intangible, particularly in anatomically complex defects. In this work, personalized and defect-specific antibiotic-laden polymeric scaffolds containing metronidazole (MET), tetracycline (TCH), or their combination (MET/TCH) were created via electrospinning. An initial screening of the synthesized fibers comprising chemo-morphological analyses, cytocompatibility assessment, and antimicrobial validation against periodontopathogens was accomplished to determine the cell-friendly and anti-infective nature of the scaffolds. According to the cytocompatibility and antimicrobial data, the 1:3 MET/TCH formulation was used to obtain three-dimensional defect-specific scaffolds to treat periodontally compromised three-wall osseous defects in rats. Inflammatory cell response and new bone formation were assessed by histology. Micro-computerized tomography was performed to assess bone loss in the furcation area at 2 and 6 weeks post implantation. Chemo-morphological and cell compatibility analyses confirmed the synthesis of cytocompatible antibiotic-laden fibers with antimicrobial action. Importantly, the 1:3 MET/TCH defect-specific scaffolds led to increased new bone formation, lower bone loss, and reduced inflammatory response when compared to antibiotic-free scaffolds. Altogether, our results suggest that the fabrication of defect-specific antibiotic-laden scaffolds holds great potential toward the development of personalized (i.e., patient-specific medication) scaffolds to ablate infection while affording regenerative properties.

Made available in DSpace on 2020-12-10T19:56:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-08 National Institutes of Health (NIH, National Institute of Dental and Craniofacial Research/NIDCR) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A photocrosslinkable gelatin methacryloyl (GelMA) hydrogel has been widely examined in regenerative engineering because of its good cell-tissue affinity and degradability in the presence of matrix metalloproteinases. A halloysite aluminosilicate nanotube (HNT) is a known reservoir for the loading and sustained delivery of therapeutics. Here, we formulate injectable chlorhexidine (CHX)-loaded nanotube-modified GelMA hydrogel that is cytocompatible and biodegradable and provides sustained release of CHX for infection ablation while displaying good biocompatibility. The effects of HNTs and CHX on hydrogel degradability and mechanical properties, as well as on the kinetics of CHX release, and on the antimicrobial efficacy against oral pathogens were systematically assessed. Cytocompatibility in stem cells from human exfoliated deciduous teeth and inflammatory response in vivo using a subcutaneous rat model were determined. Our hydrogel system, that is, (CHX)-loaded nanotube-modified GelMA showed minimum localized inflammatory responses, supporting its ability for drug delivery applications. Moreover, we showed that the incorporation of CHX-loaded nanotubes reduces the mechanical properties, increases the swelling ratio, and diminishes the degradation rate of the hydrogels. Importantly, the presence of CHX-loaded nanotubes inhibits bacterial growth with minimal cell toxicity. Our findings provide a new strategy to modify GelMA hydrogel with chlorhexidine-loaded nanotubes for clinical use as an injectable drug delivery strategy for dental infection ablation. Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA Univ Fed Pelotas, Sch Dent, Dept Restorat Dent, BR-96010610 Pelotas, RS, Brazil Sao Paulo State Univ, Sch Dent, Dept Dent Mat & Prosthodont, BR-01049010 Araraquara, SP, Brazil Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA Univ Michigan, Sch Dent, Dept Biol & Mat Sci & Prosthodont, Ann Arbor, MI 48109 USA Sao Paulo State Univ, Sch Dent, Dept Dent Mat & Prosthodont, BR-01049010 Araraquara, SP, Brazil National Institutes of Health (NIH, National Institute of Dental and Craniofacial Research/NIDCR): K08DE023552 National Institutes of Health (NIH, National Institute of Dental and Craniofacial Research/NIDCR): R01DE026578