Due to the limited capacity of cartilage in its regeneration and repair, there is a need for suitable alternative systems to imitate the natural function of the tissue in terms of physical, mechanical and histological aspects. One of these methods is the tissue engineering strategy, the main goal of which is to develop biological substitutes in order to restore, preserve or restore damaged tissue and improve the function of the natural organ. In recent decades, hydrogels have been used in cartilage tissue engineering due to their biological properties and the ability to imitate the extracellular matrix. Recently, IPN and Semi-IPN hydrogels have received much attention in the construction of tissue engineering scaffolds due to their favorable biological properties and improved mechanical performance. It has been shown that IPN hydrogel networks have higher mechanical performance than single component hydrogels. In this research, two biocompatible materials, agarose and (PEGDA), were combined to create an IPN hydrogel with enhanced properties, in the construction of cartilage tissue engineering scaffolds, by extrusion 3D printing method and the effect of different concentrations of nanohydroxyapatite on its physical, mechanical and structural properties was investigated and studied. The concentration of agarose for 3D printing of cartilage scaffold was optimized using Taguchi test design and the best concentration of nanohydroxyapatite for combination with agarose/ (PEGDA) hydrogel by comparing printability, mechanical properties and microstructure. Nanocomposite scaffolds containing 0.4, 0.8, and 1.2 (%w/v) of nanohydroxyapatite were obtained. Investigating the properties resulting from mixing nanohydroxyapatite with hydrogel in this research was done through mechanical properties tests, rheometry test, Fourier transform spectroscopy test, field emission scanning electron microscope test, and X-ray diffraction test. Also, in order to eva‎luate the swelling behavior and stability of the samples, in vitro swelling and degradability tests were performed on the samples with and without nanoparticles. The compression and tension test results of the hydrogel scaffolds showed that by adding 0.8 (%w/v) of nanohydroxyapatite to the hydrogel network, the compressive strength increased from 131 to 246 kPa and the tensile strength increased from 418 to 936 kPa. Also, the results of the rheometric test confirmed the shear-thinning behavior in both samples with and without nanoparticles, and the pre-gel viscosity increased from 3010 to 54100 kPa/s due to the addition of 0.8 (%w/v) of nanohydroxyapatite to the hydrogel network. The results of the Fourier transform spectroscopy test also confirmed the formation of the IPN network between agarose and (PEGDA) and the effect of the addition of nanohydroxyapatite on the microstructure of the hydrogel network was also investigated through field emission scanning electron microscopy. showed that the addition of 0.8 (%w/v) of nanohydroxyapatite to the IPN hydrogel network caused the formation of a regular and interconnected microstructure in the network structure. Also, the results of the in vitro swelling and degradability test showed a reduction in swelling and degradation of hydrogel samples from 291% to 176% after 24 hours and from 66% to 60% after 14 days, due to the addition of 0.8 (%w/v) showed of nanohydroxyapatite to the IPN hydrogel network. The results of L929 cell culture on hydrogel scaffolds showed the non-toxicity and biocompatibility of agarose/ (PEGDA) 3D printed scaffolds to the extent of 90.5% after 5 days of cultivation. which increased to 95.6% for nanocomposite hydrogel. According to the results obtained from this thesis, it can be said that Agarose/ (PEGDA)/ nanohydroxyapatite nanocomposite scaffold made by extrusion 3D printing method is considered a desirable and efficient structure in cartilage tissue engineering.

طيبه بهزاد , مهشيد خرازيهاي اصفهاني

محمد رفيعي نيا

سعيد نوري خراساني , فرزانه علي حسيني