Hydrogels, as three-dimensional polymeric networks with a high water absorption capacity, have gained a significant position in biomedical fields—such as tissue engineering an‎d drug delivery—due to their unique characteristics, including biocompatibility, biodegradability, an‎d structural similarity to the extracellular matrix (ECM).In this thesis, with the aim of developing biocompatible hydrogels based on thiolated hyaluronic acid (HA-SH) for soft tissue repair an‎d drug delivery systems, hyaluronic acid was selec‎ted as the base polymer an‎d chemically modified through thiolation.Functional group identification was performed using FT-IR spectroscopy, where the presence of the characteristic peak corresponding to the thiol (–SH) group confirmed the success of the modification reaction. Subsequently, proton nuclear magnetic resonance spectroscopy (^1H NMR) indicated a thiol substitution degree of approximately 20%.In the next step, to form the three-dimensional network, 8-arm polyethylene glycol maleimide (PEG-8-Mal) was used as the crosslinker. The Michael-type click addition reaction between the thiol groups of hyaluronic acid an‎d the electrophilic maleimide groups—driven by the nucleophilicity of thiols—was employed. This reaction was chosen due to its high reaction rate, selec‎tivity, an‎d compatibility with mild conditions (physiological temperature an‎d aqueous environment without the need for a catalyst).The gelation time under physiological conditions was measured to be approximately 30 seconds, indicating rapid gel formation suitable for injectable applications.Mechanical characterization using the stress–strain test demonstrated that the hydrogel exhibited a compressive modulus of 1.13 ± 0.13 kPa. Structural failure occurred at around 80% strain, consistent with the mechanical behavior of soft, biomimetic hydrogels. Oscillatory rheometry further showed that the storage modulus (G′) exceeded the loss modulus (G″) across all frequency ranges, indicating predominantly elastic, solid-like behavior.The swelling ratio of the hydrogels was measured at approximately 114%, reflecting their ability to mimic the ECM an‎d withstan‎d mechanical challenges present in biological environments.The MTS cytocompatibility assay conducted on NIH-3T3 fibroblasts showed cell viability of 85.7 ± 1.5% on day 1, 91.6 ± 4.5% on day 3, an‎d 126.4 ± 0.68% on day 5, demonstrating excellent cell proliferation an‎d compatibility within the hydrogel matrix. Additionally, stability assessments under physiological conditions indicated that the hydrogels remained intact for up to 30 days without significant degradation.Overall, the thiolated hyaluronic acid hydrogels produced via Michael addition demonstrate suitable injectability, rapid in situ gelation, favorable mechanical stability, an‎d excellent biocompatibility, making them promising can‎didates for applications such as cell scaffolds in tissue engineering an‎d controlled drug delivery systems.

سعيد نوري خراساني , محمدحسين قانيان

محمد حسين نصر اصفهاني , مرضيه تولايي

احمد اسدي نژاد , افسانه فخار