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Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models
Author(s) -
Wildt Bregje W. M.,
Meijden Robin,
Bartels Paul A. A.,
Sommerdijk Nico A. J. M.,
Akiva Anat,
Ito Keita,
Hofmann Sandra
Publication year - 2022
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202206992
Subject(s) - fibroin , bone remodeling , extracellular matrix , mineralization (soil science) , materials science , in vitro , biomedical engineering , matrix (chemical analysis) , biophysics , microbiology and biotechnology , chemistry , biology , biochemistry , silk , composite material , medicine , endocrinology , organic chemistry , nitrogen
Human in vitro bone models can create the possibility for investigation of physiological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3R). Current in vitro models lack cell–matrix interactions and their spatiotemporal complexity. To facilitate these analyses, a bone‐mimetic template is developed in this study, inspired by bone's extracellular matrix composition and organization. Silk fibroin (SF) is used as an organic matrix, poly‐aspartic acid (pAsp) is used to mimic the functionality of noncollagenous proteins, and 10× simulated body fluid serves as mineralization solution. By using pAsp in the mineralization solution, minerals are guided toward the SF material resulting in mineralization inside and as a coating on top of the SF. After cytocompatibility testing, remodeling experiments are performed in which mineralized scaffold remodeling by osteoclasts and osteoblasts is tracked with nondestructive microcomputed tomography and medium analyses over a period of 42 d. The mineralized scaffolds support osteoclastic resorption and osteoblastic mineralization, in the physiological bone remodeling specific sequence. This model could therefore facilitate the investigation of cell–matrix interactions and may thus reduce animal experiments and advance in vitro drug testing for bone remodeling pathologies like osteoporosis, where cell–matrix interactions need to be targeted.