Poli(Poliol)Sebakat Bazlı Biyobozunur Elastomerlerin Sentezi ve Jiro Eğrilmiş Fiber Destekli Hidrojel Doku İskelelerinin Geliştirilmesi
Özet
Poly(polyol) sebacate (PPS) based polymers are promising polymers in biomedical and tissue engineering field, thanks to tunable mechanical properties and having biodegradable and biocompatible features. However, difficult conditions and long duration in synthesis and also challanges in processability limit the widespread use of PPS elastomers. In this thesis study, it is aimed to overcome the difficulties in the synthesis of PPS based polymers by microwave polymerization, to improve fiber production by adding poly(ethylene glycol) (PEG) and to use them as tissue scaffolds.
By this regard, in the first part of thesis study poly(glycerol)sebacate (PGS), poly(xylitol)sebacate (PXS), poly(glycerol)sebacate-co-poly(ethylene glycol) (PGS-co-PEG) and poly(xylitol)sebacate-co-poly(ethylene glycol) (PXS-co-PEG) polymers were synthesized approximately in 4 minutes by microwave polymerization. Crosslinking time have been found to prolong in xylitol containing PXS and PXS-co-PEG polymers due to free hydroxyl groups. PEG addition to poly(polyol) sebacate polymers, the elastic modulus values decreased from 1.20±0.01 MPa to 0.060±0.004 MPa, while the % extension at break point increased from ~ 99% to ~ 160%. When the thermal properties of the polymers were examined, it was found that the glass transition temperatures were between -28.53 and -35.48 ºC and they exhibited elastic behavior at body temperature. At the same time, % mass loss increased from 4.4% to 9.3% in 21 days in the presence of PEG. It is concluded that PEG increases the amount of water uptake and the rate of hydrolytic degradation in the polymer structure. It was determined that the synthesized polymers had no toxic effect on L929 fibroblast cells.
In the second part of the thesis, PPS polymers were synthesized using electrohydrodynamic (EHD) portable gun and pressurized gyration techniques. Lower diameter (~ 1 μm) fibers were obtained with the EHD system, compared to the gyration technique and applied electrical field increased depending on the conductivity of polymer solution and surface tension. The conductivity of PGS-co-PEG and PXS-co-PEG polymer solutions was found to be increased by 3.5 times higher after PEG addition. This increase in conductivity values caused the fiber area in the collector to increase while shortening the distance in the syringe jet formation. It was determined that PPS fibers produced by EHD support cell attachment and proliferation. Especially after 7 days of PXS-co-PEG fibers, cell viability was significantly increased compared to other sample groups.
The fiber diameters produced by the pressurized gyration technique increased (~ 10 μm) compared to the fibers produced by the EHD system. It has been determined that rotation speed, pressure, solution concentration and viscosity directly affects the gyrospun fiber formation. In addition, the increased diameters of the gyrospun fibers increased the porosity of the resulting bulk structure and allowed the cells to propagate in the three-dimensional structure and were advantageous compared to the fibers produced with EHD. Fibroblast cell attachment and spreading on three-dimensional gyrospun fiber was determined by microscopic investigations.
In the last part of the thesis, gelatin methacrylate (Gel-M) hidrogel was synthesized and the swelling, degradation and viscoelastic properties were determined for hydrogels with different concentration parameters. Elastomeric PPS fiber constructs were integrated into synthesized gelatin methacrylate (Gel-M) gel and hybrid scaffolds were obtained by UV curing. Fibers reinforced hybrid tissue scaffolds support the co-cultures of fibroblast and keratinocyte cells and increase the cell viability and proliferation. As a result, it has been concluded that the hybrid tissue scaffolds have a high potential for skin tissue engineering.
