A 3D in vitro co-culture model for evaluating biomaterial-mediated modulation of foreign-body responses

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dc.authoridZhang, Yu Shrike/0000-0002-0045-0808
dc.authoridCakmak, Betul/0000-0003-1247-6295
dc.authoridYesil-Celiktas, Ozlem/0000-0003-4509-2212
dc.authorscopusid57696195500
dc.authorscopusid57204924916
dc.authorscopusid57697747800
dc.authorscopusid56191420300
dc.authorscopusid22837401200
dc.authorwosidZhang, Yu Shrike/H-4885-2013
dc.authorwosidYesil-Celiktas, Ozlem/AAI-5713-2020
dc.contributor.authorCakmak, Betul
dc.contributor.authorSaglam-Metiner, Pelin
dc.contributor.authorBeceren, Goze
dc.contributor.authorZhang, Yu S.
dc.contributor.authorYesil-Celiktas, Ozlem
dc.date.accessioned2023-01-12T19:51:56Z
dc.date.available2023-01-12T19:51:56Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractThe 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. [GRAPHICS] .en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [219M057]; TUBITAK 2211-A National Graduate Scholarship Program; TUBITAK 2210-C National Priority Areas Graduate Scholarship Program; Brigham Research Instituteen_US
dc.description.sponsorshipThis work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under the grant number 219M057. PSM acknowledges TUBITAK 2211-A National Graduate Scholarship Program and BC acknowledges TUBITAK 2210-C National Priority Areas Graduate Scholarship Program. YSZ acknowledges support by the Brigham Research Institute.en_US
dc.identifier.doi10.1007/s42242-022-00198-z
dc.identifier.endpage480en_US
dc.identifier.issn2096-5524
dc.identifier.issn2522-8552
dc.identifier.issn2096-5524en_US
dc.identifier.issn2522-8552en_US
dc.identifier.issue3en_US
dc.identifier.scopus2-s2.0-85130243185en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage465en_US
dc.identifier.urihttps://doi.org/10.1007/s42242-022-00198-z
dc.identifier.urihttps://hdl.handle.net/11454/76353
dc.identifier.volume5en_US
dc.identifier.wosWOS:000797276000001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherSpringer Heidelbergen_US
dc.relation.ispartofBio-Design And Manufacturingen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBiomaterialen_US
dc.subjectMacrophage polarizationen_US
dc.subjectGenotoxicityen_US
dc.subjectBiocompatibilityen_US
dc.subjectImmune responseen_US
dc.subjectMacrophage Polarizationen_US
dc.subjectHyaluronic-Aciden_US
dc.subjectCell-Cultureen_US
dc.subjectBiocompatibilityen_US
dc.subjectDifferentiationen_US
dc.subjectEnvironmenten_US
dc.subjectActivationen_US
dc.subjectPhenotypesen_US
dc.subjectHydrogelsen_US
dc.subjectRepairen_US
dc.titleA 3D in vitro co-culture model for evaluating biomaterial-mediated modulation of foreign-body responsesen_US
dc.typeArticleen_US

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