Date

2023-1-25

Author

Özsoy, Tuba Selenay

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Dental pulp regeneration strategies mainly focus on treating infected pulp and aiding pulp tissue formation mainly with scaffold aided approach. Incorporating a particulate delivery system like solid lipid nanoparticles (SLN) in a polymeric scaffold is an effective strategy for delivering bioactive agents in a sustained manner. In this thesis, it was aimed to develop an injectable hydrogel containing antimicrobial agent (Amoxicillin, AMOX) and regenerative bioactive agent loaded solid lipid nanoparticles for dental pulp tissue engineering. The blank, retinoic acid (RA) and 17ß-estradiol (ESDL) loaded SLNs were prepared with the solvent injection method. The particle size and zeta potential of blank SLNs were found as 43.6 ± 6.4 nm, -13.9 ± 0.3 mV, respectively. The ESDL loaded-SLNs has 63.8 ± 28.9 nm particle size, -12.5 ± 0.8 mV zeta potential, 70.2% ± 13.9 encapsulation efficiency and 93.4 ± 2.4 drug loading capacity. The 64.5% ± 2.0 of ESDL was released from SLNs within 6 h and reached to 72.3% ± 3.6 after 24 h. Cell culture studies conducted with dental pulp stem cells showed that ESDL increased their ALP activity compared to RA. Thus, SLNs were prepared only with ESDL and incorporated in the hydrogels. The chitosan/hyaluronic acid (CS/HA) hydrogels with different volume-to-volume ratios (CS1:HA1, CS1:HA2 and CS1:HA3) were produced with polyelectrolyte complex formation and crosslinking with -glycerophosphate and characterized to obtain the optimal hydrogel formulation to mimic pulp tissue. The antibacterial effect of AMOX loaded hydrogels were shown and the hydrogels showed a sudden burst release followed by a slower release. The shear thinning effect observed in shear rate sweep test showed the injectability of blank and blank SLN loaded hydrogels. Based on rheological, water uptake and weight loss studies showed that CS1:HA1 hydrogels were chosen for the incorporation of SLNs. No dose dependent cytotoxic effect of AMOX, RA and ESDL on L929 and dental pulp stem cells (DPSC) was observed as well as all hydrogel composition. The alkaline phosphatase (ALP) enzyme activity was studied for observing the odontoblastic differentiation of DPSCs. All of the ESDL concentrations induced the ALP activity. The ALP activity was the highest for the lowest ESDL concentration. On the other hand, RA has an inhibitory impact on DPSCs. Based on our results it can be concluded that the injectable CS1:HA1 hydrogel formulation containing AMOX, and ESDL loaded SLNs is expected to hold promise for infected dental pulp treatment.

Subject Keywords

Dental pulp, Lipid nanoparticles, Hydrogel, Injectable polymer, Controlled drug release

URI

https://hdl.handle.net/11511/102562

Collections

Graduate School of Natural and Applied Sciences, Thesis