Abstract:BackgroundA triple antibiotic mixture (ciprofloxacin; CF, metronidazole; MN, and minocycline; MC) has been used for dental root canal medicaments in pulp regeneration therapy. However, tooth discolorations, cervical root fractures, and inadequate pulp-dentin formation have been reported due to the triple antibiotic regimen. Therefore, an antibiotic encapsulated biomimetic nanomatrix gel was developed to minimize the clinical limitations and maximize a natural healing process in root canal infections. In this s… Show more
“…They have a prolonged action of active agent, thus they are capable of releasing drugs in a sustained and controlled manner . The method of action has been studied in nitric oxide‐releasing cardiovascular stents, cardiac tissue regeneration with growth factor and stem cell delivery, and dental revitalization with antibiotic delivery . This nanomatrix technology should be easily translatable to local therapeutic delivery in upper airway diseases including CRS.…”
Objectives
Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor systemic absorption, and minimal depletion. The objectives of the current study are to analyze the in vitro release rate and in vivo drug delivery tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent (CSS).
Methods
The CSS (2 mg) was created from biodegradable poly-D/L-lactic acid. After analyzing in vitro release profile, CSTs were placed unilaterally in maxillary sinuses of 16 rabbits via dorsal sinusotomy. Animals were sacrificed between 1 and 3 weeks postoperatively. Ciprofloxacin concentrations in the sinus tissue and plasmas were assessed using high-performance liquid chromatography. Radiological and histological evaluations were performed.
Results
In the in vitro release profile, an initial burst release was observed over the first 24 hrs, followed by sustained release through the 14 day time point. In the rabbit model, ciprofloxacin was continuously released from the stent up to 3 weeks at doses > 50 ng/ml. Histologic examination found no evidence of inflammation, epithelial ulceration or bony reaction upon sacrifice of the animals at 21 days. Computed tomography also demonstrated no signs of mucosal edema or opacification in the sinus.
Conclusion
The CST was safe in this preclinical model and sustained release was observed in both the in vitro and in vivo analyses. The innovative stent design coated with ciprofloxacin may provide a unique therapeutic strategy for CRS.
“…They have a prolonged action of active agent, thus they are capable of releasing drugs in a sustained and controlled manner . The method of action has been studied in nitric oxide‐releasing cardiovascular stents, cardiac tissue regeneration with growth factor and stem cell delivery, and dental revitalization with antibiotic delivery . This nanomatrix technology should be easily translatable to local therapeutic delivery in upper airway diseases including CRS.…”
Objectives
Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor systemic absorption, and minimal depletion. The objectives of the current study are to analyze the in vitro release rate and in vivo drug delivery tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent (CSS).
Methods
The CSS (2 mg) was created from biodegradable poly-D/L-lactic acid. After analyzing in vitro release profile, CSTs were placed unilaterally in maxillary sinuses of 16 rabbits via dorsal sinusotomy. Animals were sacrificed between 1 and 3 weeks postoperatively. Ciprofloxacin concentrations in the sinus tissue and plasmas were assessed using high-performance liquid chromatography. Radiological and histological evaluations were performed.
Results
In the in vitro release profile, an initial burst release was observed over the first 24 hrs, followed by sustained release through the 14 day time point. In the rabbit model, ciprofloxacin was continuously released from the stent up to 3 weeks at doses > 50 ng/ml. Histologic examination found no evidence of inflammation, epithelial ulceration or bony reaction upon sacrifice of the animals at 21 days. Computed tomography also demonstrated no signs of mucosal edema or opacification in the sinus.
Conclusion
The CST was safe in this preclinical model and sustained release was observed in both the in vitro and in vivo analyses. The innovative stent design coated with ciprofloxacin may provide a unique therapeutic strategy for CRS.
“…As seen in Fig. 4 , Kaushik et al have developed a biomimetic antibiotic releasing nanomatrix gel that demonstrates synergistic antibacterial effects, which may be effective for root canal disinfections and eliminates the use of minocycline, which is used in the traditional protocol [ 119 ]. The development of the gel, which uses PA for the encapsulation of the antibiotics to create a sustained local release drug delivery system, is still in preliminary stages but shows very promising results in early studies.…”
Section: Reviewmentioning
confidence: 99%
“…The developed gel, which contains ciprofloxacin and metronidazole, was tested against two prominent bacterial strains in endodontic infections , E. faecalis and T. denticola . Their results portrayed that the developed gel had a greater synergistic antibacterial effect than the antibiotics alone [ 119 ]. Fig.…”
Section: Reviewmentioning
confidence: 99%
“…Encapsulation of antibiotics, ( d ). Formation of the nanomatrix gel, Modified with permission from Kaushik et al [ 119 ] …”
Regenerative endodontics has been proposed to replace damaged and underdeveloped tooth structures with normal pulp-dentin tissue by providing a natural extracellular matrix (ECM) mimicking environment; stem cells, signaling molecules, and scaffolds. In addition, clinical success of the regenerative endodontic treatments can be evidenced by absence of signs and symptoms; no bony pathology, a disinfected pulp, and the maturation of root dentin in length and thickness. In spite of the various approaches of regenerative endodontics, there are several major challenges that remain to be improved: a) the endodontic root canal is a strong harbor of the endodontic bacterial biofilm and the fundamental etiologic factors of recurrent endodontic diseases, (b) tooth discolorations are caused by antibiotics and filling materials, (c) cervical root fractures are caused by endodontic medicaments, (d) pulp tissue is not vascularized nor innervated, and (e) the dentin matrix is not developed with adequate root thickness and length. Generally, current clinical protocols and recent studies have shown a limited success of the pulp-dentin tissue regeneration. Throughout the various approaches, the construction of biomimetic microenvironments of pulp-dentin tissue is a key concept of the tissue engineering based regenerative endodontics. The biomimetic microenvironments are composed of a synthetic nano-scaled polymeric fiber structure that mimics native pulp ECM and functions as a scaffold of the pulp-dentin tissue complex. They will provide a framework of the pulp ECM, can deliver selective bioactive molecules, and may recruit pluripotent stem cells from the vicinity of the pulp apex. The polymeric nanofibers are produced by methods of self-assembly, electrospinning, and phase separation. In order to be applied to biomedical use, the polymeric nanofibers require biocompatibility, stability, and biodegradability. Therefore, this review focuses on the development and application of the biomimetic microenvironments of pulp-dentin tissue among the current regenerative endodontics.
“…The MMP family of enzymes, produced in healthy cells, hydrolyzes most ECM proteins and promotes constant matrix remodeling by the cells [28]. Therefore, an ECM-mimicking PA nanomatrix gel can stimulate natural interactions between tissues and scaffold, and can also be used for various tissue engineering applications such as pancreatic islet transplantation, bone, tooth, and cardiac regeneration, etc [4, 24, 29, 30]. …”
For three-dimensional tissue engineering scaffolds, the major challenges of hydrogels are poor mechanical integrity and difficulty in handling during implantation. In contrast, electrospun scaffolds provide tunable mechanical properties and high porosity; but, are limited in cell encapsulation. To overcome these limitations, we developed a “hybrid nanosack” by combination of a peptide amphiphile (PA) nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures. This hybrid nanosack design synergistically possessed the characteristics of both approaches. In this study, the hybrid nanosack was applied to enhance local angiogenesis in the omentum, which is required of tissue engineering scaffolds for graft survival. The ePCL sheet with porous crater-like structures improved cell and blood vessel penetration through the hybrid nanosack. The hybrid nanosack also provided multi-stage fibroblast growth factor-2 (FGF-2) release kinetics for stimulating local angiogenesis. The hybrid nanosack was implanted into rat omentum for 14 days and vascularization was analyzed by micro-CT and immunohistochemistry; the data clearly demonstrated that both FGF-2 delivery and porous crater-like structures work synergistically to enhance blood vessel formation within the hybrid nanosack. Therefore, the hybrid nanosack will provide a new strategy for engineering scaffolds to achieve graft survival in the omentum by stimulating local vascularization, thus overcoming the limitations of current strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
