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

Bio-Design and Manufacturing 2022年第3期5卷 465-480页

作者： Betul Cakmak pelin saglam-metiner Goze Beceren Yu S.Zhang Ozlem Yesil-Celiktas Department of Bioengineering Faculty of EngineeringEge University35100 IzmirTurkey Division of Engineering in Medicine Brigham and Women’s HospitalDepartment of MedicineHarvard Medical SchoolCambridgeMAUSA

The immune response after implantation of a biomaterial may shorten the functional life of the implant,depending on the degree of the *** 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 graphiteenhanced hydrogel(PAAm-Alg-G)as a non-biocompatible counterpart,to evaluate macrophage attachment and polarization to pro-or anti-inflammatory *** 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 3.25×10^(5) cells/*** 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 *** M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G,leading to significant M1 dominance(p0.05).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 *** immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials.

关键词： Biomaterial Macrophage polarization Genotoxicity Biocompatibility Immune response

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