2024
Adv Healthc Mater. 2024 Oct 23:e2401939. doi: 10.1002/adhm.202401939.
Humanized In Vivo Bone Tissue Engineering: In Vitro Preculture Conditions Control the Structural, Cellular, and Matrix Composition of Humanized Bone Organs
School of Biomedical Sciences, Faculty of Health, and Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, 4102, Australia. Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4000, Australia. Max Planck Queensland Centre, Brisbane, QLD, 4000, Australia. Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling, and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD, 4000, Australia. Australian Prostate Cancer Research Centre (APCRC-Q), QUT, Brisbane, QLD, 4102, Australia. Central Analytical Research Facility, QUT, Brisbane, QLD, 4102, Australia. Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany. Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia. Australian Research Council (ARC) Training Centre for Cell and Tissue Engineering Technologies (CTET), QUT, Brisbane, QLD, 4000, Australia.
Service type: Stock strains
Abstract
Bone tissue engineering (BTE) has long sought to elucidate the key factors controlling human/humanized bone formation for regenerative medicine and disease modeling applications, yet with no definitive answers due to the high number and co-dependency of parameters. This study aims to clarify the relative impacts of in vitro biomimetic 'preculture composition' and 'preculture duration' before in vivo implantation as key criteria for the optimization of BTE design. These parameters are directly related to in vitro osteogenic differentiation (OD) and mineralization and are being investigated across different osteoprogenitor-loaded biomaterials, specifically fibrous calcium phosphate-polycaprolactone (CaP-mPCL) scaffolds and gelatin methacryloyl (GelMA) hydrogels. The results show that OD and mineralization levels prior to implantation, enhanced by a mineralization medium supplement to the osteogenic medium (OM), significantly improve ectopic BTE outcomes, regardless of the biomaterial type. Specifically, preculture conditions are pivotal in achieving more faithful mimicry of human bone structure, cellular and extracellular matrix composition and organization, and provide control over bone marrow composition. This work emphasizes the potential of using biomimetic culture compositions, specifically the addition of a mineralization medium as a cost-effective and straightforward approach to enhance BTE outcomes, facilitating rapid development of bone models with superior quality and resemblance to native bone.
Keywords: bone structure; bone tissue engineering (BTE); extracellular matrix; humanized mouse model; in vivo bone model; mineralization; osteogenic differentiation (OD).
