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The field of tissue engineering has witnessed significant advancements in recent years, driven by the pursuit of innovative solutions to address the challenges of bone regeneration. In this study, we developed an electrospun composite scaffold for bone tissue engineering. The composite scaffold is made of a blend of poly(L‐lactide‐co‐ε‐caprolactone) (PLCL) and polyethylene glycol (PEG), with the incorporation of calcined and lyophilized silicate‐chlorinated bioactive glass (BG) particles. Our investigation involved a comprehensive characterization of the scaffold's physical, chemical, and mechanical properties, alongside an evaluation of its biological efficacy employing alveolar bone‐derived mesenchymal stem cells. The incorporation of PEG and BG resulted in elevated swelling ratios, consequently enhancing hydrophilicity. Thermal gravimetric analysis confirmed the efficient incorporation of BG, with the scaffolds demonstrating thermal stability up to 250°C. Mechanical testing revealed enhanced tensile strength and Young's modulus in the presence of BG; however, the elongation at break decreased. Cell viability assays demonstrated improved cytocompatibility, especially in the PLCL/PEG+BG group. Alizarin red staining indicated enhanced osteoinductive potential, and fluorescence analysis confirmed increased cell adhesion in the PLCL/PEG+BG group. Our findings suggest that the PLCL/PEG/BG composite scaffold holds promise as an advanced biomaterial for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Pulp capping is a necessary procedure for preserving the vitality and health of the dental pulp, playing a crucial role in preventing the need for root canal treatment or tooth extraction. Here, we developed an electrospun gelatin methacryloyl (GelMA) fibrous scaffold incorporating beta-tricalcium phosphate (TCP) particles for pulp capping. A comprehensive morphological, physical-chemical, and mechanical characterization of the engineered fibrous scaffolds was performed. In vitro bioactivity, cell compatibility, and odontogenic differentiation potential of the scaffolds in dental pulp stem cells (DPSCs) were also evaluated. A pre-clinical in vivo model was used to determine the therapeutic role of the GelMA/TCP scaffolds in promoting hard tissue formation. Morphological, chemical, and thermal analyses confirmed effective TCP incorporation in the GelMA nanofibers. The GelMA+20%TCP nanofibrous scaffold exhibited bead-free morphology and suitable mechanical and degradation properties. In vitro , GelMA+20%TCP scaffolds supported apatite-like formation, improved cell spreading, and increased deposition of mineralization nodules. Gene expression analysis revealed upregulation of ALPL, RUNX2, COL1A1, and DMP1 in the presence of TCP-laden scaffolds. In vivo , analyses showed mild inflammatory reaction upon scaffolds' contact while supporting mineralized tissue formation. Although the levels of Nestin and DMP1 proteins did not exceed those associated with the clinical reference treatment (i.e., mineral trioxide aggregate), the GelMA+20%TCP scaffold exhibited comparable levels, thus suggesting the emergence of differentiated odontoblast-like cells capable of dentin matrix secretion. Our innovative GelMA/TCP scaffold represents a simplified and efficient alternative to conventional pulp-capping biomaterials. Vital pulp therapy (VPT) aims to preserve dental pulp vitality and avoid root canal treatment. Biomaterials that bolster mineralized tissue regeneration with ease of use are still lacking. We successfully engineered gelatin methacryloyl (GelMA) electrospun scaffolds incorporated with beta-tricalcium phosphate (TCP) for VPT. Notably, electrospun GelMA-based scaffolds containing 20% (w/v) of TCP exhibited favorable mechanical properties and degradation, cytocompatibility, and mineralization potential indicated by apatite-like structures in vitro and mineralized tissue deposition in vivo, although not surpassing those associated with the standard of care. Collectively, our innovative GelMA/TCP scaffold represents a simplified alternative to conventional pulp capping materials such as MTA and Biodentine™ since it is a ready-to-use biomaterial, requires no setting time, and is therapeutically effective. [Display omitted] [ABSTRACT FROM AUTHOR]

This study was aimed at engineering photocrosslinkable azithromycin (AZ)-laden gelatin methacryloyl fibers via electrospinning to serve as a localized and biodegradable drug delivery system for endodontic infection control. AZ at three distinct amounts was mixed with solubilized gelatin methacryloyl and the photoinitiator to obtain the following fibers: GelMA+5%AZ, GelMA+10%AZ, and GelMA+15%AZ. Fiber morphology, diameter, AZ incorporation, mechanical properties, degradation profile, and antimicrobial action against Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii were also studied. In vitro compatibility with human-derived dental pulp stem cells and inflammatory response in vivo using a subcutaneous rat model were also determined. A bead-free fibrous microstructure with interconnected pores was observed for all groups. GelMA and GelMA+10%AZ had the highest fiber diameter means. The tensile strength of the GelMA-based fibers was reduced upon AZ addition. A similar pattern was observed for the degradation profile in vitro. GelMA+15%AZ fibers led to the highest bacterial inhibition. The presence of AZ, regardless of the concentration, did not pose significant toxicity. In vivo findings indicated higher blood vessel formation, mild inflammation, and mature and thick well-oriented collagen fibers interweaving with the engineered fibers. Altogether, AZ-laden photocrosslinkable GelMA fibers had adequate mechanical and degradation properties, with 15%AZ displaying significant antimicrobial activity without compromising biocompatibility. [ABSTRACT FROM AUTHOR]

This study evaluated the biocompatibility of degradable polydioxanone (PDS) electrospun drug delivery systems (hereafter referred as matrices) containing metronidazole (MET) or ciprofloxacin (CIP) after subcutaneous implantation in rats. Sixty adult male rats were randomized into six groups: SHAM (sham surgery); PDS (antibiotic‐free matrix); 1MET (one 25 wt% MET matrix); 1CIP (one 25 wt% CIP matrix); 2MET (two 25 wt% MET matrices); and 2CIP (two 25 wt% CIP matrices). At 3 and 30 days, animals were assessed for inflammatory cell response (ICR), collagen fibers degradation, and oxidative profile (reactive oxygen species [ROS]; lipid peroxidation [LP]; and protein carbonyl [PC]). At 3 days, percentages of no/discrete ICR were 100, 93.3, 86.7, 76.7, 50, and 66.6 for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP, respectively. At 30 days, percentages of no/discrete ICR were 100% for SHAM, PDS, 1MET, and 1CIP and 93.3% for 2MET and 2CIP. Between 3 and 30 days, SHAM, 1CIP, and 2CIP produced collagen, while 1MET and 2MET were unchanged. At 30 days, the collagen fiber means percentages for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP were 63.7, 60.7, 56.6, 62.6, 51.8, and 61.7, respectively. Antibiotic‐eluting matrices showed similar or better oxidative behavior when compared to PDS, except for CIP‐eluting matrices, which showed higher levels of PC compared to SHAM or PDS at 30 days. Collectively, our findings indicate that antibiotic‐eluting matrices may be an attractive biocompatible drug delivery system to fight periodontopathogens. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019. [ABSTRACT FROM AUTHOR]

Curcumin incorporation into polymeric fibers was tested for its antimicrobial properties and potential use in root canal disinfection. Curcumin-modified fibers were processed via electrospinning and tested against a 7-day old established Actinomyces naeslundii biofilm. The medicaments tested were as follows: curcumin-modified fibers at 2.5 and 5.0 mg/mL, curcumin-based irrigant at 2.5 and 5.0 mg/mL, saline solution (negative control), and the following positive controls: 2% chlorhexidine, 1% sodium hypochlorite, and triple antibiotic paste (TAP, 1 mg/mL). All medicaments, except for the positive controls, were allocated according to the light exposure protocol (ie, photoactivation with a light-emitting diode every 30 seconds for 4 minutes or without photoactivation). After treatment, the medicaments were removed, and 1 mL saline solution was added; the biofilm was scraped from the well and used to prepare a 1:2000 dilution. Spiral plating was performed using anaerobic blood agar plates. After 24 hours, colony-forming units (colony-forming units/mL, n = 11/group) were counted to determine the antimicrobial effects. Data exhibited significant antimicrobial effects on the positive control groups followed by the curcumin irrigants and, lastly, the photoactivated curcumin-modified fibers. There was a significant reduction of viable bacteria in curcumin-based irrigants, which was greater than the TAP-treated group. Curcumin-free fibers, saline, and the nonphotoactivated curcumin-modified fibers did not display antimicrobial activity. Curcumin seems to be a potential alternative to TAP when controlling infection, but it requires a minimal concentration (2.5 mg/mL) to be effective. Photoactivation of curcumin-based medicaments seems to be essential to obtain greater antibiofilm activity. [ABSTRACT FROM AUTHOR]

Evoked bleeding (EB) clinical procedure, comprising a disinfection step followed by periapical tissue laceration to induce the ingrowth of undifferentiated stem cells from the periodontal ligament and alveolar bone, is currently the only regenerative‐based therapeutic approach to treating pulp tissue necrosis in undeveloped (immature) permanent teeth approved in the United States. Yet, the disinfection step using antibiotic‐based pastes leads to cytotoxic, warranting a biocompatible strategy to promote root canal disinfection with no or minimal side‐effects to maximize the regenerative outcomes. The purpose of this investigation was to develop a tubular three‐dimensional (3D) triple antibiotic‐eluting construct for intracanal drug delivery. Morphological (scanning electron microscopy), chemical (Fourier transform infrared spectroscopy), and mechanical (tensile testing) characteristics of the polydioxanone‐based triple antibiotic‐eluting fibers were assessed. The antimicrobial properties of the tubular 3D constructs were determined in vitro and in vivo using an infected (Actinomyces naeslundii) dentin tooth slice model and a canine method of periapical disease, respectively. The in vitro data indicated significant antimicrobial activity and the ability to eliminate bacterial biofilm inside dentinal tubules. In vivo histological findings demonstrated that, using the EB procedure, the tubular 3D triple antibiotic‐eluting construct allowed the formation of an appropriate environment that led to apex closure and the ingrowth of a thin layer of osteodentin‐like tissue into the root canal. Taken together, these findings indicate that our novel drug delivery construct is a promising biocompatible disinfection strategy for immature permanent teeth with necrotic pulps. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1576–1586, 2019. [ABSTRACT FROM AUTHOR]

Introduction A biocompatible strategy to promote bacterial eradication within the root canal system after pulpal necrosis of immature permanent teeth is critical to the success of regenerative endodontic procedures. This study sought to synthesize clindamycin-modified triple antibiotic (metronidazole, ciprofloxacin, and clindamycin [CLIN]) polymer (polydioxanone [PDS]) nanofibers and determine in vitro their antimicrobial properties, cell compatibility, and dentin discoloration. Methods CLIN-only and triple antibiotic CLIN-modified (CLIN-m, minocycline-free) nanofibers were processed via electrospinning. Scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and tensile testing were performed to investigate fiber morphology, antibiotic incorporation, and mechanical strength, respectively. Antimicrobial properties of CLIN-only and CLIN-m nanofibers were assessed against several bacterial species by direct nanofiber/bacteria contact and over time based on aliquot collection up to 21 days. Cytocompatibility was measured against human dental pulp stem cells. Dentin discoloration upon nanofiber exposure was qualitatively recorded over time. The data were statistically analyzed ( P < .05). Results The mean fiber diameter of CLIN-containing nanofibers ranged between 352 ± 128 nm and 349 ± 128 nm and was significantly smaller than PDS fibers. FTIR analysis confirmed the presence of antibiotics in the nanofibers. Hydrated CLIN-m nanofibers showed similar tensile strength to antibiotic-free (PDS) nanofibers. All CLIN-containing nanofibers and aliquots demonstrated pronounced antimicrobial activity against all bacteria. Antibiotic-containing aliquots led to a slight reduction in dental pulp stem cell viability but were not considered toxic. No visible dentin discoloration upon CLIN-containing nanofiber exposure was observed. Conclusions Collectively, based on the remarkable antimicrobial effects, cell-friendly, and stain-free properties, our data suggest that CLIN-m triple antibiotic nanofibers might be a viable alternative to minocycline-based antibiotic pastes. [ABSTRACT FROM AUTHOR]

This study investigated the antimicrobial and osteogenic properties of titanium (Ti) disks superficially modified with tetracycline (TCH)-incorporated polymer nanofibers. The experiments were carried out in two phases. The first phase dealt with the synthesis and characterization (i.e., morphology, mechanical strength, drug release, antimicrobial activity, and cytocompatibility) of TCH-incorporated fibers. The second phase was dedicated to evaluating both the antimicrobial and murine-derived osteoprecursor cell (MC3T3-E1) response of Ti-modified with TCH-incorporated fibers. TCH was successfully incorporated into the submicron-sized and cytocompatible fibers. All TCH-incorporated mats presented significant antimicrobial activity against periodontal pathogens. The antimicrobial potential of the TCH-incorporated fibers-modified Ti was influenced by both the TCH concentration and bacteria tested. At days 5 and 7, a significant increase in MC3T3-E1 cell number was observed for TCH-incorporated nanofibers-modified Ti disks when compared to that of TCH-free nanofibers-modified Ti-disks and bare Ti. A significant increase in alkaline phosphatase (ALP) levels on the Ti disks modified with TCH-incorporated nanofiber on days 7 and 14 was seen, suggesting that the proposed surface promotes early osteogenic differentiation. Collectively, the data suggest that TCH-incorporated nanofibers could function as an antimicrobial surface modifier and osteogenic inducer for Ti dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2085-2092, 2017. [ABSTRACT FROM AUTHOR]

Introduction Root canal disinfection and the establishment of an intracanal microenvironment conducive to the proliferation/differentiation of stem cells play a significant role in regenerative endodontics. This study was designed to (1) investigate the antimicrobial efficacy of triple antibiotic–containing nanofibers against a dual-species biofilm and (2) evaluate the ability of dental pulp stem cells (DPSCs) to adhere to and proliferate on dentin upon nanofiber exposure. Methods Seven-day-old dual-species biofilm established on dentin specimens was exposed for 3 days to the following: saline (control), antibiotic-free nanofibers (control), and triple antibiotic–containing nanofibers or a saturated triple antibiotic paste (TAP) solution (50 mg/mL in phosphate buffer solution). Bacterial viability was assessed using the LIVE/DEAD assay (Molecular Probes, Inc, Eugene, OR) and confocal laser scanning microscopy. For cytocompatibility studies, dentin specimens after nanofiber or TAP (1 g/mL in phosphate buffer solution) exposure were evaluated for cell adhesion and spreading by actin-phalloidin staining. DPSC proliferation was assessed on days 1, 3, and 7. Statistics were performed, and significance was set at the 5% level. Results Confocal laser scanning microscopy showed significant bacterial death upon antibiotic-containing nanofiber exposure, differing significantly ( P < .05) from antibiotic-free fibers and the control (saline). DPSCs showed enhanced adhesion/spreading on dentin specimens treated with antibiotic-containing nanofibers when compared with its TAP counterparts. The DPSC proliferation rate was similar on days 1 and 3 in antibiotic-free nanofibers, triple antibiotic–containing nanofibers, and TAP-treated dentin. Proliferation was higher (9-fold) on dentin treated with antibiotic-containing nanofibers on day 7 compared with TAP. Conclusions Triple antibiotic–containing polymer nanofibers led to significant bacterial death, whereas they did not affect DPSC attachment and proliferation on dentin. [ABSTRACT FROM AUTHOR]

Composite fibrous electrospun membranes based on poly( dl-lactide) (PLA) and poly(ε-caprolactone) (PCL) were engineered to include borate bioactive glass (BBG) for the potential purposes of guided bone regeneration (GBR). The fibers were characterized using scanning and transmission electron microscopies, which respectively confirmed the submicron fibrous arrangement of the membranes and the successful incorporation of BBG particles. Selected mechanical properties of the membranes were evaluated using the suture pullout test. The addition of BBG at 10 wt % led to similar stiffness, but more importantly, it led to a significantly stronger (2.37 ± 0.51 N mm) membrane when compared with the commercially available Epiguide® (1.06 ± 0.24 N mm) under hydrated conditions. Stability (shrinkage) was determined after incubation in a phosphate buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL-based membranes with or without BBG incorporation (10.07-16.08%) was similar to that of Epiguide (14.28%). Cell proliferation assays demonstrated a higher rate of preosteoblasts proliferation on BBG-containing membranes (6.4-fold) over BBG-free membranes (4- to 5.8-fold) and EpiGuide (4.5-fold), following 7 days of in vitro culture. Collectively, our results demonstrated the ability to synthesize, via electrospinning, stable, polymer-based submicron fibrous BBG-containing membranes capable of sustaining osteoblastic attachment and proliferation-a promising attribute in GBR. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 594-605, 2016. [ABSTRACT FROM AUTHOR]

Introduction: Although intracanal application of the triple antibiotic paste (TAP) may offer advantages (eg, disinfection), this practice has been associated with significant drawbacks, including tooth discoloration. In this study, the color change of dentin was monitored during treatment with distinct TAP pastes and novel tubularshaped 3-dimensional electrospun scaffolds containing minocycline (MINO) or doxycycline (DOX). Methods: Two TAP pastes (TAPM|NO [MINO, metronidazole, and ciprofloxacin] and TAPDOX [DOX, metronidazole, and ciprofloxacin]), 4 scaffold-based groups containing MINO or DOX at distinct concentrations, 1 antibioticfree scaffold, and 1 untreated group (control) were investigated. Human canines were sectioned at the cementoenamel junction and tubular-shaped scaffolds or paste were placed into the root canals and sealed. Color measurements (CIEL*a*b* parameters) were performed at baseline and after 1, 3, 7, 14, 21, and 28 days. Color changes were expressed as DE* values. In addition, scanning electron microscopy and energydispersive X-ray spectroscopy were also performed on the specimens after treatment. Data were analyzed using repeated measures analysis of variance (alpha = 0.05). Results: All antibiotic-containing groups led to greater discoloration than the antibiotic-free groups. A severe discoloration occurred after 1 day. At the end of the experiment, antibiotic-treated samples exhibited crusts/agglomerates over the dentin surface, which totally or partially obliterated the dentinal tubules. The presence of MINO resulted in a greater color change than DOX. Conclusions: Scaffolds containing MINO or DOX produced similar color change to dentin when compared with their respective TAP systems, although DOX-related discoloration was less pronounced. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate resinbased experimental dental sealants containing electrospun nylon-6 (N6) and chitosan (CH) fibers in an attempt to improve the physicomechanical properties and provide an antibacterial protective effect, respectively. Electrospun N6 and CH mats were immersed into a resin mixture, lightcured, and then cryomilled to obtain micron-sized resinmodified fiber particles. Different levels of the novel cryomilled particles (i.e. 1, 2.5, and 5% relative to the resin mixture, % by weight) were used to prepare the N6- and CHcontaining sealants. A commercial sealant and the experimental resin mixture (unfilled) were used as controls. Flexural strength (FS), Vickers microhardness (VH), and agar diffusion tests were performed. The data were analyzed at the 5% significance level. No significant difference in fiber diameter of N6 (503 ± 31 nm) and CH (595 ± 38 nm) was observed. Upon cryomilling, the resin-modified CH and N6 mats led to the formation of irregularly-shaped particles, with an average diameter of 14.24 µm and 15.87 µm, respectively. CH-5% had significantly higher FS (115.3 ± 1.3 MPa) than all the other groups. CH-1% had significantly higher hardness values (38.3 ± 0.3 VHN) than all the other groups. Collectively, the results indicated that CH-containing sealants presented the highest FS and hardness; however, none of the CHcontaining sealants displayed antimicrobial properties. [ABSTRACT FROM AUTHOR]

Introduction Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)–mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Methods Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm 3 , n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Results Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly ( P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant ( P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. Conclusions Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics. [ABSTRACT FROM AUTHOR]

Introduction Antibiotic-containing polymer-based nanofibers (hereafter referred to as scaffolds) have demonstrated great potential for their use in regenerative endodontics from both an antimicrobial and cytocompatibility perspective. This study sought to evaluate in vitro the effects of ciprofloxacin (CIP)-containing polymer scaffolds against Enterococcus faecalis biofilms. Methods Human mandibular incisors were longitudinally sectioned to prepare radicular dentin specimens. Sterile dentin specimens were distributed in 24-well plates and inoculated with E. faecalis for biofilm formation. Infected dentin specimens were exposed to 3 groups of scaffolds, namely polydioxanone (PDS) (control), PDS + 5 wt% CIP, and PDS + 25 wt% CIP for 2 days. Colony-forming units (CFU/mL) ( n = 10) and scanning electron microscopy (SEM) ( n = 2) were performed to quantitatively and qualitatively assess the antimicrobial effectiveness, respectively. Results PDS scaffold containing CIP at 25 wt% showed maximum bacteria elimination with no microbial growth, differing statistically ( P < .05) from the control (PDS) and from PDS scaffold containing CIP at 5 wt%. Statistical differences ( P < .05) were also seen for the CFU/mL data between pure PDS (5.92–6.02 log CFU/mL) and the PDS scaffold containing CIP at 5 wt% (5.39–5.87 log CFU/mL). SEM images revealed a greater concentration of bacteria on the middle third of the dentin specimen after 5 days of biofilm formation. On scaffold exposures, SEM images showed similar results when compared with the CFU/mL data. Dentin specimens exposed to PDS + 25 wt% CIP scaffolds displayed a practically bacteria-free surface. Conclusions On the basis of the data presented, newly developed antibiotic-containing electrospun scaffolds hold promise as an intracanal medicament to eliminate biofilm/infection before regenerative procedures. [ABSTRACT FROM AUTHOR]

Introduction Eliminating and/or inhibiting bacterial growth within the root canal system has been shown to play a key role in the regenerative outcome. The aim of this study was to synthesize and determine in vitro both the antimicrobial effectiveness and cytocompatibility of bimix antibiotic-containing polydioxanone-based polymer scaffolds. Methods Antibiotic-containing (metronidazole [MET] and ciprofloxacin [CIP]) polymer solutions (distinct antibiotic weight ratios) were spun into fibers as a potential mimic to the double antibiotic paste (DAP, a MET/CIP mixture). Fiber morphology, chemical characteristics, and tensile strength were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, and tensile testing, respectively. Antimicrobial efficacy was tested over time (aliquot collection) against Enterococcus faecalis (Ef), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn). Similarly, cytotoxicity was evaluated in human dental pulp stem cells. Data were statistically analyzed ( P < .05). Results Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed that electrospinning was able to produce antibiotic-containing fibers with a diameter mostly in the nanoscale. The tensile strength of 1:1MET/CIP scaffolds was significantly ( P < .05) higher than pure polydioxanone (control). Meanwhile, all other groups presented similar strength as the control. Aliquots obtained from antibiotic-containing scaffolds inhibited the growth of Ef, Pg, and Fn, except pure MET, which did not show an inhibitory action toward Pg or Fn. Antibiotic-containing aliquots promoted slight human dental pulp stem cell viability reduction, but none of them were considered to be cytotoxic. Conclusions Our data suggest that the incorporation of multiple antibiotics within a nanofibrous scaffold holds great potential toward the development of a drug delivery system for regenerative endodontics. [ABSTRACT FROM AUTHOR]

This 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. [ABSTRACT FROM AUTHOR]

Abstract: Periodontitis is a major chronic inflammatory disorder that can lead to the destruction of the periodontal tissues and, ultimately, tooth loss. To date, flap debridement and/or flap curettage and periodontal regenerative therapy with membranes and bone grafting materials have been employed with distinct levels of clinical success. Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue down-growth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural, mechanical, and bio-functional limitations and the “ideal” membrane for use in periodontal regenerative therapy has yet to be developed. Based on a graded-biomaterials approach, we have hypothesized that the next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes for periodontal tissue engineering will be a biologically active, spatially designed and functionally graded nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). Objective: This review is presented in three major parts, including (1) a brief overview of the periodontium and its pathological conditions, (2) currently employed therapeutics used to regenerate the distinct periodontal tissues, and (3) a review of commercially available GTR/GBR membranes as well as the recent advances on the processing and characterization of GTR/GBR membranes from a materials perspective. Significance: Studies of spatially designed and functionally graded membranes (FGM) and in vitro antibacterial/cell-related research are addressed. Finally, as a future outlook, the use of hydrogels in combination with scaffold materials is highlighted as a promising approach for periodontal tissue engineering. [Copyright &y& Elsevier]

Abstract: A periodontal membrane with a graded structure allows tailoring of the layer properties to design a material system that will retain its physical, chemical and mechanical characteristics for a period long enough to optimize periodontal regeneration. In this work a novel functionally graded membrane (FGM) was designed and fabricated via sequential multilayer electrospinning. The FGM consists of a core layer (CL) and two functional surface layers (SLs) interfacing with bone (nano-hydroxyapatite, n-HAp) and epithelial (metronidazole, MET) tissues. The CL comprises a neat poly(dl-lactide-co-ε-caprolactone) (PLCL) layer surrounded by two composite layers composed of a protein/polymer ternary blend (PLCL:PLA:GEL). Electrospinning parameters involved in fabrication of the individual layers (i.e. neat PLCL, ternary blend, PLA:GEL+10%n-HAp and PLA:GEL+25%MET) were optimized to obtain fibrous layers free of beads. Morphology, structure and mechanical property studies were carried out on each electrospun layer. The individual fiber morphology and roughness of the functional SLs, which are the n-HAp containing and drug-incorporating layers were evaluated by atomic force microscopy. The CL structure demonstrated higher strength (8.7MPa) and a more elastic behavior (strain at break 357%) compared with the FGM (3.5MPa, 297%). Incorporation of n-HAp to enhance osteoconductive behavior and MET to combat periodontal pathogens led to a novel FGM that holds promise at solving the drawbacks of currently available membranes. [ABSTRACT FROM AUTHOR]

This study aimed to synthesize and characterize non-woven acrylonitrile butadiene styrene (ABS), polyamide-6 (P6), and polystyrene (PS) nanofibers, and evaluate their effects on the flexural strength and fracture resistance of fiber-modified polymethyl methacrylate (PMMA) resin. ABS, P6, and PS polymer solutions were prepared and electrospun into fiber mats, which were characterized by means of morphological, chemical, physical, and mechanical analyses. The fiber mats were then used to modify a thermally-activated PMMA resin, resulting in four testing groups: one unmodified group (control) and three fiber-modified groups incorporated with ABS, P6, or PS fiber mats. Flexural strength, work of fracture, and fractographic analysis were performed for all groups. Data were analyzed using Kruskal-Wallis or ANOVA tests (α = 0.05). The fiber diameter decreased, respectively, as follows: ABS > P6 > PS. Only the P6 fiber mats demonstrated a crystalline structure. Wettability was similar among the distinct fiber mats, although tensile strength was significantly greater for P6, followed by ABS, and then PS mats. Flexural strength of the fiber-modified PMMA resins was similar to the control, except for the weaker P6-based material. The work of fracture seemed to be greater and lower when the P6 and PS fibers were used, respectively. The fiber-modified groups exhibited a rougher pattern in the fractured surfaces when compared to the control, which may suggest that the presence of fibers deviates the direction of crack propagation, making the fracture mechanism of the PMMA resin more dynamic. While the neat PMMA showed a typical brittle response, the fiber-modified PMMA resins demonstrated a ductile response, combined with voids, suggesting large shear deformation during fracture. Altogether, despite the lack of direct reinforcement in the mechanical strength of the PMMA resin, the use of electrospun fibers showed promising application for the improvement of fracture behavior of PMMA resins, turning them into more compliant materials, although this effect may depend on the fiber composition. [ABSTRACT FROM AUTHOR]

The elimination of microbial flora in cases of immature permanent teeth with necrotic pulp is both key and a challenging goal for the long-term success of regenerative therapy. Recent research has focused on the development of cell-friendly intracanal drug delivery systems. This in vitro study aimed to investigate the antimicrobial action of 3-dimensional (3D) tubular-shaped triple antibiotic–eluting nanofibrous constructs against a multispecies biofilm on human dentin. Polydioxanone polymer solutions, antibiotic-free or incorporated with metronidazole, ciprofloxacin, and minocycline, were electrospun into 3D tubular-shaped constructs. A multispecies biofilm consisting of Actinomyces naeslundii , Streptococcus sanguinis , and Enterococcus faecalis was forced inside the dentinal tubules via centrifugation in a dentin slice in vitro model. The infected specimens were exposed to 2 experimental groups (ie, 3D tubular-shaped triple antibiotic–eluting constructs and triple antibiotic paste [TAP]) and 2 control groups (7-day biofilm untreated and antibiotic-free 3D tubular-shaped constructs). Biofilm elimination was quantitatively analyzed with confocal laser scanning microscopy. Confocal laser scanning microscopic (CLSM) analysis showed a dense population of viable (green) bacteria adhered to dentin and penetrated into the dentinal tubules. Upon 3D tubular-shaped triple antibiotic–eluting nanofibrous construct exposure, nearly complete elimination of viable bacteria on the dentin surface and inside the dentinal tubules was shown in the CLSM images, which was similar ( P < .05) to the bacterial death promoted by the TAP group but significantly greater when compared with both the antibiotic-free 3D tubular-shaped constructs and the control (saline). The proposed 3D tubular-shaped antibiotic-eluting construct showed pronounced antimicrobial effects against the multispecies biofilm tested and therefore holds significant clinical potential as a disinfection strategy before regenerative endodontics. [ABSTRACT FROM AUTHOR]

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 P 11 -4 has emerged as a promising strategy to induce mineralization; however, P 11 -4 application has been mostly addressed for early caries lesions repair on dental enamel. Here, to investigate P 11 -4′s efficacy on bone regeneration, polymeric electrospun scaffolds were developed, and then distinct concentrations of P 11 -4 were physically adsorbed on the scaffolds. P 11 -4-laden and pristine (P 11 -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 P 11 -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 P 11 -4 did not affect the fibers' diameter. SEM images indicated mineral precipitation, while FTIR and XRD confirmed apatite-like formation and crystallization for P 11 -4-laden scaffolds. In addition, P 11 -4-laden scaffolds were cytocompatible, highly stimulated cell-mediated mineral deposition, and upregulated the expression of mineralization-related genes compared to pristine scaffolds. P 11 -4-laden scaffolds led to enhanced in vivo bone regeneration after 8 weeks compared to pristine PCL. Electrospun scaffolds functionalized with P 11 -4 are a promising strategy for inducing mineralized tissues regeneration in the craniomaxillofacial complex. [Display omitted] • Self-assembly peptide P 11 -4-laden scaffolds induces mineral precipitation. • P 11 -4-laden scaffolds stimulate stem cells to mineral deposition. • P 11 -4-laden scaffolds upregulate osteogenic markers. • P 11 -4-laden scaffolds induces bone formation in vivo. [ABSTRACT FROM AUTHOR]

From a materials perspective, the pillars for the development of clinically translatable scaffold-based strategies for craniomaxillofacial (CMF) bone and periodontal regeneration have included electrospinning and 3D printing (biofabrication) technologies. Here, we offer a detailed analysis of the latest innovations in 3D (bio)printing strategies for CMF bone and periodontal regeneration and provide future directions envisioning the development of advanced 3D architectures for successful clinical translation. First, the principles of electrospinning applied to the generation of biodegradable scaffolds are discussed. Next, we present on extrusion-based 3D printing technologies with a focus on creating scaffolds with improved regenerative capacity. In addition, we offer a critical appraisal on 3D (bio)printing and multitechnology convergence to enable the reconstruction of CMF bones and periodontal tissues. As a future outlook, we highlight future directions associated with the utilisation of complementary biomaterials and (bio)fabrication technologies for effective translation of personalised and functional scaffolds into the clinics. [ABSTRACT FROM AUTHOR]

Objectives This study reports on the synthesis, materials characterization, antimicrobial capacity, and cytocompatibility of novel ZnO-loaded membranes for guided tissue/bone regeneration (GTR/GBR). Methods Poly(ɛ-caprolactone) (PCL) and PCL/gelatin (PCL/GEL) were dissolved in hexafluoropropanol and loaded with ZnO at distinct concentrations: 0 (control), 5, 15, and 30 wt.%. Electrospinning was performed using optimized parameters and the fibers were characterized via scanning and transmission electron microscopies (SEM/TEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), contact angle (CA), mechanical testing, antimicrobial activity against periodontopathogens, and cytotoxicity test using human dental pulp stem cells (hDPSCs). Data were analyzed using ANOVA and Tukey ( α = 5%). Results ZnO nanoparticles were successfully incorporated into the overall submicron fibers, which showed fairly good morphology and microstructure. Upon ZnO nanoparticles’ incorporation, the PCL and PCL/GEL fibers became thicker and thinner, respectively. All GEL-containing membranes showed lower CA than the PCL-based membranes, which were highly hydrophobic. Overall, the mechanical properties of the membranes were reduced upon ZnO incorporation, except for PCL-based membranes containing ZnO at the 30 wt.% concentration. The presence of GEL enhanced the stretching ability of membranes under wet conditions. All ZnO-containing membranes displayed antibacterial activity against the bacteria tested, which was generally more pronounced with increased ZnO content. All membranes synthesized in this study demonstrated satisfactory cytocompatibility, although the presence of 30 wt.% ZnO led to decreased viability. Significance Collectively, this study suggests that PCL- and PCL/GEL-based membranes containing a low content of ZnO nanoparticles can potentially function as a biologically safe antimicrobial GTR/GBR membrane. [ABSTRACT FROM AUTHOR]

• A drug delivery system to afford sustained release of DEX was achieved by CD-IC. • DEX/CD-IC was successfully incorporated into PLGA fibers via electrospinning. • UPLC revealed the solubility enhancement and sustained release of DEX by CD-IC. • Cell compatibility and proliferation was more favorable in DEX/CD-IC fibers. • Odonto/osteogenic differentiation was enhanced in DEX/CD-IC electrospun fibers. Beta-cyclodextrin (β-CD) is an oligosaccharide commonly used to improve the aqueous solubility of lipophilic drugs (e.g., dexamethasone, DEX). Here we present the development of a drug delivery system to provide sustained release of DEX by β-CD-inclusion complex (IC) to amplify the mineralization capacity of stem cells from human-extracted deciduous teeth (SHEDs) as a potential direct pulp capping strategy. First, IC of DEX (DEX-CD-IC) was synthesized with β-CD. To confirm DEX-CD-IC complex formation, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses were performed. XRD data indicated that IC formation was achieved due to formation of a new crystalline structure, whereas FTIR revealed the presence of the IC from the shifting of the peaks of each component in DEX-CD-IC. Then, electrospun poly(lactic-co-glycolic acid, PLGA) fibers (PLGA/DEX-CD-IC) were processed by varying the concentration of DEX-CD-IC (5%, 10 %, and 15 %). The release of DEX from fibers was determined by ultraperformance liquid chromatography for 28 days. Thanks to the solubility enhancement of DEX by IC, electrospun PLGA/DEX-CD-IC fibers released DEX in a more sustained fashion compared to PLGA/DEX fibers. No deleterious effect was found in terms of SHEDs' proliferation when cultured with or on electrospun fibers, regardless of the IC presence. Importantly, a more pronounced odontogenic differentiation was stimulated by electrospun fibers loaded with the lowest DEX-CD-IC concentration (5%), as a result of the sustained DEX release. In sum, PLGA/DEX-CD-IC fibers have great potential in vital dental pulp therapy, owing to its sustained DEX release, cytocompatibility, and odontogenic differentiation capacity. [ABSTRACT FROM AUTHOR]