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

• Published in: Bio-design and manufacturing 2022-07, Vol.5 (3), p.465-480
• Main Authors: Cakmak, Betul, Saglam-Metiner, Pelin, Beceren, Goze, Zhang, Yu S., Yesil-Celiktas, Ozlem
• Format: Article
• Language: English
• Subjects: Alginic acid; Antibodies; Biocompatibility; Biomaterials; Biomedical Engineering and Bioengineering; Biomedical materials; Cell culture; Cell viability; Chondrocytes; Cytokines; Cytotoxicity; Engineering; Extracellular matrix; Fibroblasts; Gelatin; Genotoxicity; Hemodialysis; Hyaluronic acid; Hydrogels; Immune response; Immune system; Immunomodulation; Inflammation; Interleukin 10; Interleukin 6; Leukocyte migration; Macrophages; Mechanical Engineering; Phenotypes; Polyacrylamide; Research Article; Research methodology; Risk assessment; Sodium; Spectrum analysis; Tumor necrosis factor-TNF
• ISSN: 2096-5524; 2522-8552
• DOI: 10.1007/s42242-022-00198-z

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 × 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   0.05). The interleukin-6 (IL-6) concentration secreted in the presence of PAAm-Alg hydrogel (4.58 pg/mL) significantly decreased ( p