1 Ocak 2022 Dergi makalesi Açık Erişim

Cakmak, Betul; Saglam-Metiner, Pelin; Beceren, Goze; Zhang, Yu S.; Yesil-Celiktas, Ozlem

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        "affiliation": "Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey", 
        "name": "Cakmak, Betul"
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      {
        "affiliation": "Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey", 
        "name": "Saglam-Metiner, Pelin"
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      {
        "affiliation": "Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey", 
        "name": "Beceren, Goze"
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      {
        "affiliation": "Harvard Med Sch, Div Engn Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA USA", 
        "name": "Zhang, Yu S."
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      {
        "affiliation": "Ege Univ, Dept Bioengn, Fac Engn, TR-35100 Izmir, Turkey", 
        "name": "Yesil-Celiktas, Ozlem"
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    "description": "The immune response after implantation of a biomaterial may shorten the functional life of the implant, depending on the degree of the response. In this study, we used a polyacrylamide-alginate (PAAm-Alg) hydrogel, which has been previously characterized as a biocompatible material and shown to enhance regeneration of cartilage in vivo, along with a graphite-enhanced hydrogel (PAAm-Alg-G) as a non-biocompatible counterpart, to evaluate macrophage attachment and polarization to pro- or anti-inflammatory phenotypes. The performance of each biomaterial in the presence of fibroblasts and chondrocytes was validated by an in vitro model which demonstrated modulation of the foreign-body response. A blend of 5% gelatin methacryloyl and 0.1% methacrylated hyaluronic acid was optimized to mimic the extracellular matrix (ECM) and support cell viability, proliferation, migration, and functionality at an initial concentration of 3.25 x 10(5) cells/mL. The PAAm-Alg-G hydrogel localized in the simulated ECM showed cytotoxic and genotoxic effects for both fibroblasts and chondrocytes, while exhibiting a proliferative effect on macrophages with elevated immune response. The M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G, leading to significant M1 dominance (p < 0.0001), as expected, on day 13. Moreover, loading PAAm-Alg hydrogel with transforming growth factor beta-3 (TGF-beta 3) resulted in a slightly more balanced M1/M2 ratio of 0.87 (p > 0.05). The interleukin-6 (IL-6) concentration secreted in the presence of PAAm-Alg hydrogel (4.58 pg/mL) significantly decreased (p < 0.0001) on day 13, while the increase (p < 0.0001) in interleukin-10 (IL-10) concentration (120.73 pg/mL) confirmed the switch from a pro-inflammatory to an anti-inflammatory response. Predicting immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials.", 
    "doi": "10.1007/s42242-022-00198-z", 
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    "journal": {
      "issue": "3", 
      "pages": "465-480", 
      "title": "BIO-DESIGN AND MANUFACTURING", 
      "volume": "5"
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    "publication_date": "2022-01-01", 
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    "title": "A 3D in vitro co-culture model for evaluating biomaterial-mediated modulation of foreign-body responses"
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