For hydrogel injection applications, it is important to improve the strength and biostability of the hydrogel as well as its injectability to pass easily through the needle. Making gel microspheres is one approach to achieve these improvements. Granulization of a bulk hydrogel is a common procedure used to form microsized particles; however, the nonuniform size and shape cause an uneven force during injection, damaging the surrounding tissue and causing pain to the patients. In this study, injectable hyaluronic acid (HA)-based hybrid hydrogel microspheres were fabricated using a water-in-oil emulsion process. The injectability was significantly enhanced because of the relatively uniform size and spherical shape of the hydrogel formulates. In addition, the biostability and mechanical strength were also increased owing to the increased cross-linking density compared with that of conventionally fabricated gel microparticles. This tendency was further improved after in situ calcium phosphate precipitation. Our findings demonstrate the great potential of HA-based hydrogel microspheres for various clinical demands requiring injectable biomaterials.
Background: The authors investigated the synergistic effects of adipose-derived stem cells and fat graft on skin wrinkles in a nude mouse model of chronologic aging. Methods: After 50 weeks of chronologic aging, 44 female BALB/c nude mice were classified into four groups: (1) negative control, (2) mice injected subcutaneously with fat on the back skin (0.5 cm3), (3) mice injected with adipose-derived stem cells (1 × 105 cells in 0.5 cm3 Hanks balanced salt solution), and (4) mice injected with both fat (0.5 cm3) and adipose-derived stem cells (1 × 105 cells in 0.5 cm3 Hanks balanced salt solution). The degree of wrinkling was evaluated using replica analysis, and skin biopsies were performed after 4 weeks. The dermal thickness and density of collagen were determined. Type I procollagen and matrix metalloproteinase levels were determined using real-time polymerase chain reaction and Western blot analysis. Tropoelastin, fibrillin-1, and CD31 levels were evaluated using immunohistochemistry. Results: Based on the total wrinkle area, there was significant wrinkle reduction in the fat-treated and adipose-derived stem cell with fat–treated groups. Type I procollagen mRNA and collagen levels were significantly higher in the adipose-derived stem cell with fat–treated group than in the adipose-derived stem cell–treated and the fat-treated groups. In addition, the adipose-derived stem cells with fat graft group exhibited significantly higher CD31 expression level than the adipose-derived stem cell–treated and the fat-treated groups. Conclusion: Both adipose-derived stem cells and fat graft have a wrinkle-reducing effect and synergistically affect collagen synthesis and neovascularization.
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