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 105 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-β3)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.

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

Department of Bioengineering,Faculty of Engineering,Ege University,35100 Izmir,Turkey;Division of Engineering in Medicine,Brigham and Women's Hospital,Department of Medicine,Harvard Medical School,Cambridge,MA,USA

生物设计与制造（英文）

[1]Betul Cakmak;Pelin Saglam-Metiner;Goze Beceren;Yu S.Zhang;Ozlem Yesil-Celiktas-.A 3D in vitro co-culture model for evaluating biomaterial-mediated modulation of foreign-body responses)[J].生物设计与制造（英文）,2022(03):465-480

methacrylated

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