Jie Jin a,1, Utkarsh Mangal a,1, Ji-Young Seo a, Ji-Yeong Kim a, Jeong-Hyun Ryu a, Young-Hee Lee b, Cerjay Lugtu c, Geelsu Hwang c d, Jung-Yul Cha a, Kee-Joon Lee a, Hyung-Seog Yu a, Kwang-Mahn Kim e, Sungil Jang b, Jae-Sung Kwon e, Sung-Hwan Choi a
aDepartment of Orthodontics, Institute of Craniofacial Deformity, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
bDepartment of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Jeonbuk National University, Jeonju-si, 54907, Republic of Korea
cDepartment of Preventive and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
dCenter for Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, United States
eDepartment and Research Institute of Dental Biomaterials and Bioengineering, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
1These authors have co-first authorship based on equal contributions.
Corresponding authors: Sungil Jang, Jae-Sung Kwon, Sung-Hwan Choi
Poly-(methyl methacrylate) (PMMA) is the preferred biomaterial for orofacial prostheses used for the rehabilitation of naso-palatal defects. However, conventional PMMA has limitations determined by the complexity of the local microbiota and the friability of oral mucosa adjacent to these defects. Our purpose was to develop a new type of PMMA, i-PMMA, with good biocompatibility and better biological effects such as higher resistance to microbial adhesion of multiple species and enhanced antioxidant effect. The addition of cerium oxide nanoparticles to PMMA using a mesoporous nano-silica carrier and polybetaine conditioning, resulted in an increased release of cerium ions and enzyme mimetic activity, without tangible loss of mechanical properties. Ex vivo experiments confirmed these observations. In stressed human gingival fibroblasts, i-PMMA reduced the levels of reactive oxygen species and increased the expression of homeostasis-related proteins (PPARg, ATG5, LCI/III). Furthermore, i-PMMA increased the levels of expression of superoxide dismutase and mitogen-activated protein kinases (ERK and Akt), and cellular migration. Lastly, we demonstrated the biosafety of i-PMMA using two in vivo models: skin sensitization assay and oral mucosa irritation test, respectively. Therefore, i-PMMA offers a cytoprotective interface that prevents microbial adhesion and attenuates oxidative stress, thus supporting physiological recovery of the oral mucosa.