Seramik Faz İçeren Yumuşak Doku Ogmentasyon Jellerinin Hazırlanması ve Karakterizasyonu

Abstract

Various factors such as trauma, ultraviolet radiation, nutritional deficiencies, and aging can lead to tissue loss, atrophy of the skin and subcutaneous tissue, and connective tissue weakness, resulting in soft tissue-related clinical issues. Similar conditions may also arise from congenital dermatological and connective tissue disorders. To address these issues, a range of materials have been developed for external skin application or as subcutaneous fillers, aimed at repairing soft tissue, reducing wrinkles, and restoring volume and tonus. Dietary supplements for systemic use are also under investigation. Further studies are ongoing to develop new materials and improve existing ones. In order to contribute to these efforts, the objective of this thesis study was to develop an injectable subcutaneous implant material designed with a unique formulation for soft tissue repair and augmentation.

The material was prepared by dispersing the calcium hydroxyapatite (Ca-HAp) ceramic phase in a carrier gel formed from carboxymethyl cellulose (CMC), glycerol, and water for injection. The biocompatibility, biodegradability, and bioactive nature of the synthesized material components have been confirmed both within the scope of the present study and by numerous studies in the literature. The gel formulation was subjected to comprehensive characterization through a range of analytical techniques. The chemical structure of the augmentation material and its components was analyzed using Fourier transform infrared spectroscopy (FTIR), while the crystal phases and structural properties of the ceramic particles were determined through X-ray diffraction (XRD). Furthermore, the thermal stability and degradation behaviors of the formulation were evaluated through thermogravimetric analysis (TGA). The surface morphology and size distribution of the Ca-HAp particles were observed by scanning electron microscopy (SEM), and it was confirmed that the particle sizes were approximately between 20 and 60 micrometers. The elemental analysis demonstrated that the Ca/P ratio within the hydroxyapatite structure was 1.65. This stoichiometric ratio was evaluated as indicative of the contribution of the ceramic phase to the efficacy, biocompatibility, and bioactivity of the final product, in accordance with the existing literature. The ICP-MS analysis indicated that the material was suitable for surgical implant use and did not raise any concerns regarding heavy metal content. Rheological analyses revealed storage modulus values of 58.6 and 68.9 kPa, and loss modulus values of 21.7 and 24.8 kPa at 2 and 5 Hz frequencies, respectively. The data indicated that the material would remain in the intended anatomical region without migrating and would possess mechanical properties comparable to those of the surrounding tissue.

Following the completion of the aforementioned tests, which encompassed morphological, chemical, thermal, and rheological aspects, the developed material was subjected to a cytotoxicity analysis within the context of in vitro studies. The cell viability percentages were determined to be 87.34% for 5 mg/mL and 61.38% for 10 mg/mL. The evaluation demonstrated that the samples did not exhibit any indications of cytotoxicity at the administered doses. They were observed to facilitate an optimal milieu for cellular growth and proliferation and to serve as a scaffold in conjunction with the microenvironment. The material, for which biocompatibility was established through MTT analysis, was evaluated in comparison with a commercial positive control sample within the context of a rat subcutaneous augmentation experimental model. In vivo experiments were conducted in which 150 μL of sterilized Ca-HAp/CMC gel was injected subcutaneously into the backs of rats. Subsequently, the gel was subjected to histological and histomorphometrical evaluation in comparison with a positive control product. The histological findings demonstrated that the Ca-HAp/CMC gel synthesized provided notable increases in dermal thickness, elastic fiber, and collagen density. At the conclusion of the 120th day, the collagen density exhibited a 12.77% increase, while the elastic fiber density demonstrated a 9.64% increase in comparison to the control group. Histomorphometric analyses revealed that this material promotes fibroblastic growth and the synthesis of new collagen and elastin. In conclusion, the results of this study confirm that the Ca-HAp/CMC augmentation gel, synthesized with a special formulation, exhibits biocompatibility, biostimulatory activity, and is non-immunogenic and non-toxic. Furthermore, no significant side effects or complications were observed. The developed material was successfully integrated into the implanted anatomical region in vivo, supported fibroblastic growth, and demonstrated the capacity to provide three-dimensional volumetric stability by promoting new collagen formation. In light of these findings, our material has demonstrated the potential to serve as a promising option for soft tissue repair and augmentation.